Neutrons, magnets, and photons: a career in structural biology

The purpose of Reflections articles, it seems, is to give elderly scientists a chance to write about the "good old days," when everyone walked to school in the snow. They enjoy this activity so much that your editor, Martha Fedor, must have known that I would accept her invitation to write such an article, no matter how much I demurred at first. As everyone knows, flattery will get you everywhere. It may comfort the apprehensive reader to learn that there is not going to be much walking to school in the snow in this story. On the contrary, rather than thinking how hard I had it during my scientific career, I find it inconceivable that anyone could have had a smoother ride. At the time I began my career, science was an expanding enterprise in the United States that welcomed the young. Only in such an opportunity-rich environment would someone like me have stood a chance. The contrast between that world and the dog-eat-dog world young scientists confront today is stark.     

How to do it. Participate in an international conference.

Attending an international conference should be instructive and fun. But it can also be alarming and lonely. Although participating in scientific conferences is now almost essential to medical career development, no medical school describes how to make the most of the opportunity as part of its curriculum. Here are some hints on how to get yourself organised so that the experience can be both scientifically productive and enjoyable. In essence, you should travel, see places, meet people, make friends, and identify one or two ideas that you can apply in your own work or research.     

Transition from academia to industry: a personal account

A career in industry has become a widely accepted alternative for those of us trained in medicine and/or science who have traditionally focused on careers in academia. Like any career decision, consideration of a position in industry should include asking yourself a series of fundamental questions. A few of the key questions should include: 1) What kind of work environment do you find most enjoyable? (e.g., patient care setting, basic research lab, team-oriented setting); 2) What are you focused on accomplishing in your career? (basic research discoveries, contributions to clinical medicine, compensation); 3) Are you team oriented in your interactions or are you more of an individual contributor? A successful career in any endeavor, including industry, starts with a careful and honest examination of what you are best suited for and inspired to do.     

Who owns your body? Legal issues on the ownership of bodily material

Who owns your body and parts removed from it? Can you legally sell your bodily material – or information derived from it? Can you legally prevent other people gaining access to your excised bodily material, including your blood relatives who might need your tissue or genetic information for their own genetic tests? What legal remedies are there if people take or use your bodily material without your consent? And why are the answers to these questions vitally important for scientists?     

Fifteen compelling open questions in plant cell biology

As scientists, we are at least as excited about the open questions—the things we do not know—as the discoveries. Here, we asked 15 experts to describe the most compelling open questions in plant cell biology. These are their questions: How are organelle identity, domains, and boundaries maintained under the continuous flux of vesicle trafficking and membrane remodeling? Is the plant cortical microtubule cytoskeleton a mechanosensory apparatus? How are the cellular pathways of cell wall synthesis, assembly, modification, and integrity sensing linked in plants? Why do plasmodesmata open and close? Is there retrograde signaling from vacuoles to the nucleus? How do root cells accommodate fungal endosymbionts? What is the role of cell edges in plant morphogenesis? How is the cell division site determined? What are the emergent effects of polyploidy on the biology of the cell, and how are any such “rules” conditioned by cell type? Can mechanical forces trigger new cell fates in plants? How does a single differentiated somatic cell reprogram and gain pluripotency? How does polarity develop de-novo in isolated plant cells? What is the spectrum of cellular functions for membraneless organelles and intrinsically disordered proteins? How do plants deal with internal noise? How does order emerge in cells and propagate to organs and organisms from complex dynamical processes? We hope you find the discussions of these questions thought provoking and inspiring.

We asked 15 experts to address what they consider to be the most compelling open questions in plant cell biology and these are their questions.     

In Lieu of an Introduction

Nikolai Veresov: Tatiana, in this volume of our journal we publish a selection of your articles. Two of your other articles were published in Soviet Psychology in the 1970s. Introducing you to the readers of that journal, James Wertsch (1978) wrote: "The author … is one of the leading young investigators from the Luria school of neurolinguistics. She has studied and conducted extensive research both with Luria and with A. A. Leontiev, a major figure in Soviet psycholinguistics. Her analysis of inner speech as a mechanism in speech production reveals the strong influence that L. S. Vygotsky has had on Soviet psychology."¹ But first of all, I suppose our readers would be interested in learning more about your life, about events that preceded your scientific achievements. Could you please tell us briefly about your childhood and your family? How did your parents influence your course of life and your occupational choice? What did they do?     

Walking between academia and industry to find successful solutions to biomedical challenges: an interview with Geoffrey Smith

Geoffrey W. Smith is currently the Managing Director of Mars Ventures. He actually started his studies with a Bachelor of Arts degree and a Doctorate in Law but then, in part by chance and in part by following in his family footsteps, he stepped into the healthcare and biotech field. Since then, he has successfully contributed to the birth of a number of healthcare companies and has also held academic positions at the Icahn School of Medicine at Mount Sinai and at The Rockefeller University in New York, teaching about the interface between science and business. During 2014 he served as Senior Editor on Disease Models & Mechanisms, bringing to the editorial team his valuable experience in drug development and discovery. In this interview, Geoff talks to Ross Cagan, Editor-in-Chief of Disease Models & Mechanisms, about how he developed his incredibly varied career, sharing his views about industry, academia and science publishing, and discussing how academia and industry can fruitfully meet to advance bioscience, train the scientists and stakeholders of the future, and drive the successful discovery of new therapeutics to treat human disease.Geoffrey W. Smith was born in 1965. He obtained a Bachelor of Arts degree from Williams College in Williamstown, MA. After a stint as a Research Associate at Harvard Business School, he graduated from the University of Pennsylvania Law School. Following a federal court clerkship and first job experiences in law, he joined a healthcare services start-up named Advanced Health as one of its first employees. Geoff then co-founded various healthcare and technology companies, including Interbind and Ascent Biomedical Ventures, and is still a Managing Partner at the latter. In 2012, he joined the Icahn School of Medicine at Mount Sinai, first as Professor in the Department of Population Health Science And Policy, and then as Director and co-founder of the Design, Technology, and Entrepreneurship PhD program. Until December 2014, he was a Senior Editor at Disease Models & Mechanisms. Geoff is now Managing Director of Mars Ventures.Let''s start with your background. You have a Bachelor of Arts degree and a law degree. How is it exactly that you ended up working in biotech and pharma?My career path has been anything other than linear. I was actually pursuing my legal career when two entrepreneurs turned up at the law firm I was working for with an idea for a new technology-based company focused on more effectively managing healthcare services. I was a new associate without much to do, so I got assigned to work with the start-up and after about a year they asked me to come and join the company, Advanced Health. I had grown up in a very medically oriented family – my father was a medical school professor, my older sister was a PhD, and my younger sister is a medical doctor – and so to a certain extent joining a start-up in the healthcare space was a bit like joining the family business.We had a fair amount of success with that company. A little less than 2 years after I joined it, we had a successful initial public offering, and that started me down the road of participating in the start-up environment around healthcare.It sounds like it was not a surprising path for you. Which key people influenced you?Actually, it is somewhat surprising in that I had really prepared for and expected a career in law. Certainly, the work I did in law school and the first jobs I had after that started me on a different career. I was really focused on international relations and international law. The twist was that I got brought back into the healthcare arena, and ultimately the biotech arena, by a serendipitous connection – one of the entrepreneurs who started Advanced Health had trained at Brigham Women''s Hospital where my father was the Chief of Cardiology. It was through this connection that I became more than just an associate drafting legal documents and really began to build a close relationship with the founders, which ultimately led to me joining that business. This taught me that you can spend much of your time preparing, and thinking that your schooling is going to take you in one direction, but individual relationships can change your path and take you somewhere else altogether. In my case, these particular relationships stemmed from my father, who clearly had an enormous influence on me. He was both a practising clinician and a basic researcher, studying basic biology related to the function of sodium and potassium in the heart, but he also did applied research. He helped develop a radioimmunoassay test to measure digitalis levels in the blood and ultimately was involved in developing a drug called Digibind, an antidote to digitalis toxicity, which was one of the first drugs to use antigen-binding fragments [Fab] as the basis for a drug. Watching him manage these different activities in his career had a big influence on me.

“This taught me that you can spend much of your time preparing, and thinking that your schooling is going to take you in one direction, but individual relationships can change your path and take you somewhere else altogether”

I think that each of my sisters – as I said, one of whom went down a PhD route and one of whom went down a medical training route – had a big influence on me, as well. Watching the challenges that they had to face in those areas in some ways pushed me to go off towards law school and take a different path. It also brought me back to one of the aspects that I think is the most rewarding in the bioscience field, which is that you can have a profound impact on a large number of people through your efforts, whether they be purely research-based, academic-based or commercially-based.One of the things I was constantly impressed by is that you always seem to have a good feel for the health field and the biology field. Is this because it is something of a family business?I think so. Growing up at my dinner table, I was just privileged to get to meet and interact with a lot of incredibly successful clinicians and researchers. For me those were comfortable conversations: these were friends and so there was a comfort level being involved in that environment. I didn''t feel a lot of intimidation from it, which I think sometimes people who come from the outside do.One of the aspects I really like about the bioscience field is the impact of ideas. Success is really about one''s ideas and ability to execute them, and that was very appealing to me. It wasn''t about how much money you had or where you went to school, it was really about the ability to think deeply about a problem or a potential advancement and figure out a way to find a way forward. It is also a very people-driven process because it is not only about thinking deeply yourself but also about thinking deeply with those in your field or adjacent to your field. Lots of different personality types can succeed in this field, but I think it is certainly easier for people who have an affinity for sitting with people and thinking about a common area of interest.To that point, you actually have walked between business and scientists. What do you see is the difference? Some of the priorities are obvious, but what are the differences in terms of what motivates people in the two? Are the personalities that you come across different between the basic science world, the translating science world and the business world?I don''t think the personalities are particularly different. I think you find introverts and extroverts and everything in between in each of these areas. I am not sure that personality is necessarily a good predictor of success. I think it''s a question of what toolset you are most comfortable using to get at a problem, and where in the lifespan of a problem you''re interested in working.For example, scientists in academia very often are interested in working at an early stage of a problem. They understand something fairly basic about a process or something earlier in the understanding of a field. People who gravitate towards industry, instead, are more excited about working on the later part of a process, so, rather than trying to understand what the fundamental working mechanism is, they want to understand how to work that mechanism in a way that is predictable and repeatable.Obviously people in the commercial realm are often highly influenced by money, but even that I don''t think is really particularly the differentiator. There are plenty of academics who are driven by money as well. I really think it has much more to do with where on the spectrum of understanding one is interested in working. Industry is geared to solving practical problems and, if a lot is understood about a problem, to getting down to the ability to repeatedly and safely intervene, whereas academia really lends itself more towards understanding the front end of a problem or of an unknown mechanism to understand it first and at a more basic level.What about working in teams versus individually? Do you see a difference there?I think that has changed over time. I think it is very hard in academia today to be the brilliant solo investigator. I''m not saying it''s impossible but, considering the increasing size of the data sets one is working with, the statistical methods one has to use, the complexity of different fields overlapping with each other, it''s just very hard to handle all the necessary aspects of modern science as an individual. Increasingly, working in teams isn''t a choice: I think it''s a necessity in order to be effective. The difference may be that, in academia, often the teams are teams of collaborators (meaning they have influence but not necessarily power over all people participating in the team) who may work for different institutions, whereas, more commonly in industry, teams are working within a single corporate structure. In industry more often there are hierarchical relationships, which may allow for more directive behavior. Again, I''m not sure I would draw as much distinction between team or not team and between industry and academia, but I might draw somewhat of a distinction between how those teams function and how one manages a team. I think they are a bit different between the two realms.

“Increasingly, working in teams isn''t a choice: I think it''s a necessity in order to be effective”

Let''s turn to Disease Models & Mechanisms [DMM], where you have been a Senior Editor. What did your experience at DMM teach you about science publishing that perhaps you hadn''t thought about, and has it made you think more deeply about what goes into a good scientific piece of work? What were some of the surprises?Watching the detailed process that is necessary to take a piece from an initial submission through to a published article gave me comfort and respect for the level of diligence and the level of attention that the reviewers brought to the vast majority of the pieces. It gave me a good feeling that the science community can be a strong self-reinforcing organization that takes its responsibility to heart and only publishes the best of the work available. I think that was very reassuring.An interesting question for me was: is there a different function that the publication process could play in helping to galvanize new ideas or new interactions among different fields? That seemed to be challenging because people don''t want to rush out there without their ideas and data being fully thought-out and fully vetted. But still, somewhere in my mind is this notion that there should be an option in the publishing world to play a little bit earlier in the generation of new ideas.Do you mean journals having an earlier relationship – earlier in the experimental process with a laboratory – to work with them to provide advice?I don''t know if it''s to provide advice. One of the things I was struck by at DMM is that there are these different siloed research communities – for example, the fly and the fish communities – in which interactions and relationships in the individual fields are so well established and routinized. And the outcome from a publishing standpoint is still the canonical academic paper that has been relatively unchanged over a long period of time. Yet, we have had these tremendous changes in information and communication technology such that the manner of knowledge production and the methods of communicating in other parts of society have changed dramatically. It feels like there hasn''t been nearly as big a concomitant communication change in the biomedical sciences, and so the silos and the standard paper remain the way things are done.The publication process, because of its preciseness, can take quite a long time, so the musing here is whether there is a way that the publishing industry could facilitate an earlier, more speculative communication of interesting results in a way that would positively impact the field by turning over new information sooner. If you look at an area like maths, for example, and their pre-print servers, there is more of a notion of putting ideas out in the community that acts as a kind of peer-review process and a way to get the community interacting on new ideas early. That doesn''t seem to get a lot of attention in the life sciences area. It seems to me that even journals like the PLOS journals that are pushing towards a more open world of communication are still ending up being pulled back into the canonical paper form to communicate.

“…the musing here is whether there is a way that the publishing industry could facilitate an earlier, more speculative communication of interesting results in a way that would positively impact the field by turning over new information sooner”

I guess one of the issues on the biology side is that there is a real emphasis on trying to get your paper into the most prestigious journal, so people don''t want to drop that paper until it is as far along as possible to aim at high-impact journals.That of course becomes a self-reinforcing system. If the yardstick used in the life sciences industry is publication in high-impact-rated journals, then you are going to get that behavior. But if you''re interested in the generation of new knowledge and in moving your field forwards, it is at least plausible that publishing in a quicker fashion or with at least some outlet to move more creative ideas ahead would be attractive.There are clearly challenges to that. But I do think it''s remarkable that if you look at almost every other media area there has been a huge amount of change since the advent of the internet era, but there really has been very limited change around life sciences publishing. It''s been surprisingly conservative to me. I am wishing there would be more experimentation to find other ways to communicate information sooner and in a way that could spur more creativity.Of course, when you tie publishing back to industry, for competitive and intellectual property protection reasons, industry tends to not really want to get out in the front with its most interesting work too early. I think that a lot of things being published out of industry are not the most interesting stuff that is happening. But again it seems to me that another area that science publishing should be thinking about is how they could come up with other solutions that might provide for a more creative interaction between publishing and industry.Talking about old models versus new models, let''s move to issues of training. Another area that you''ve been impressive at is the training of scientists. You''ve had your hand in creating a new PhD track at Mount Sinai called Design, Technology, and Entrepreneurship [DTE]. What is your view about how we train scientists, what we''re doing better these days and what you would like to see being done better to train them?It seemed to me that there was a remarkably small amount of experimentation in academia around thinking about how to train biomedical PhDs, and that academia had missed the opportunity to provide a better set of tools to PhDs to allow them to be effective across a wider range of potential career outcomes. The majority of biomedical PhDs are not ending up in tenure-track faculty positions but rather in the ‘alternative career track’. It seemed to be disingenuous to train them solely for the academic track if in reality the majority were going to some other career track.So what I was really excited about in putting together the DTE program was trying new ways to train PhDs to be effective askers of questions and proposers of solutions, and to create an environment where they could gain experience in how to solve a variety of problems effectively.

“…what I was really excited about in putting together the DTE program was trying new ways to train PhDs to be effective askers of questions and proposers of solutions, and to create an environment where they could gain experience in how to solve a variety of problems effectively”

This meant that our students had to be rigorously trained as scientists, but this was an ‘and’ opportunity and not an ‘or’ opportunity. In addition to being trained as excellent basics scientists, we wanted to give them some training in how engineers think about problems, how designers approach issues, what tools those people use and how that impacts how they try to solve a problem. Hopefully over time this would produce students that are better suited for interacting and influencing other parts of society – be it industry, government or policy – and better positioned to compete in what is a very competitive job market.What were some of the things you did in the DTE training to get at this?We really tried to teach theory in the context of real problems. Virtually all the classes of the DTE curriculum were problem-driven. We created a class that we called ‘The Q.E.D. Project’ that followed along from efforts at Stanford and elsewhere to teach students how to identify an unmet need. We then asked them to form a team to address the unmet need, and then helped them understand how to build a prototype to address that need. Along the way, we also talked about what kind of roles people in their team need to play. Should your team be very diverse or very deep in a given area? How do we integrate people who have different cultural backgrounds or how do we integrate medical students with PhD students? We brought in a lot of people out of the non-academic environment who were practitioners and experts in their various areas and we tried to get students to think about the full range of stakeholders they would have to engage with to bring a solution to bear.We did not want to spend a lot of time lecturing the students in a purely didactic way. We wanted to engage them in a process where they were solving important problems as part of the class. Whether that was a class on modelling or an engineering-focused class, or how to think about scientific problems, the core of DTE was built around getting the students to grapple with a real world problem and let all the learning hang off that.How did the students respond to that? Do you think you were successful?Based on the number of students signing up to take the courses and the student evaluations after the classes were over, I think we really struck a chord. I wouldn''t say it was necessarily the right answer for every student but I think there is clearly a group of students for whom this is a really effective and motivating approach.Let''s now move to drug discovery and development – the focus of the new online Special Collection from DMM. What would you say are some of the most urgent challenges in drug development that you have seen?I think one of the most urgent challenges is to begin to break free of some of our ‘old’ ways of thinking and take advantage of new scientific insights. For example, if you look at the traditional organization in a medical school environment, they are centered around departments devoted to organs (liver, heart, kidney). I think our increasing scientific understanding is that there are disease processes that may impact multiple organ systems but ultimately it is understanding the process, and drugging the process, that becomes important and not drugging the organ.I think that moving towards a process-oriented understanding of what common mechanisms are implicated in a given disease state or therapeutic challenge will help us be a little more creative and a little bit more interdisciplinary in how we think about these challenges.One of the difficulties with those new approaches is that pharmaceutical companies and academic institutions have not had a great track record of working together. Do you think that''s true? And why do you think it''s been so difficult to move ideas from the bench to the clinics?I think this is complicated. If you take the academic researchers'' point of view, their early identification of a problem and early identification of a potential solution feels like they have moved the ball very far forward towards the end solution. If you take industry''s point of view, the identification of the target or even the identification of a potential chemical compound is really just barely beginning to get to the starting line; the bulk of the time and the bulk of the dollars that will ultimately be needed to create a product come after the academic work and these will be spent by industry. I think that this differing point of view around where and how value is created has a lot to do with many of the challenges that arise when academia and industry are speaking to each other.Is it important to bridge this gap or is everybody playing their role?I think there''s an opportunity for academia to continue in its current role but to carry the potential solution further. I think in certain areas the access to tools and to patients allows academics to maybe carry projects further and closer to ‘proof of concept’ than they did historically, and that will continue to add value to the academic institution. That would ultimately help to bridge this gap because if you''ve taken something closer to proof of concept while still within the academic institution, you have created more value, you are able to engage with industry differently, and maybe the value perception gap is closed somewhat.What industry is really good at is organizing and managing late-stage research and clinical trials in an effective manner, and what academia is really good at is understanding basic questions, finding targets and sometimes finding early chemical compounds. Again, I think that the perception in academia of where value has been created is in part related to the fact that many academics haven''t been given the exposure or the training to actually understand the full breadth of the drug-development process. While they may have a general sense of it – we have all seen the same diagrams showing the steps and the funnel narrowing down from a million compounds to something getting onto the market – only those with real exposure to the work in industry understand it at a visceral or experiential level. One of the opportunities for academia is to find better ways to have some cross-talk, whether that''s internships for graduate students to get some experience in industry or other ways to get the students really exposed to the industrial side of drug development. Obviously, all the trained scientists on the industry side have been through academia because they had to go through it to get their PhDs, and thus they understand the academic side of the house pretty well. I really think the challenge is getting to people who have spent their whole career in academia to have a better understanding of what the drivers are on the industry side.

“One of the opportunities for academia is to find better ways to have some cross-talk, whether that''s internships for graduate students to get some experience in industry or other ways to get the students really exposed to the industrial side of drug development”

Between target identification and clinical trials of course there is another piece. At what point does the researcher in academia put down his pipette, walk out and start a biotech company? Should that happen?That''s a fraught question because I think it is an enormous undertaking to start a biotechnology company. Fundraising, intellectual property, regulatory affairs, company management – there are a whole number of disciplines that biotech companies have to take on. It is very rare that an academic scientist is going to have the training, the time and the motivation to do all of those things while also continuing to pursue their academic career in a very challenging funding environment. I think it comes back to this point that we were talking about with teams. I think it is really important for a scientist who is excited about their work and thinks it may be the basis of a company to go out and begin to form a team that is going to increase the likelihood of success. They have to accept the fact that science is a critical component, but it is just a component, and many different disciplines along with many different people are needed to make a successful company. If a scientist can bring that sort of collaborative view point and is open to working closely with an intellectual property attorney, with a business development person and with whomever their funding source is, that will increase their likelihood of success. They have to do it with a certain amount of humility, which is to say that it isn''t just going to be the science that drives the success: all the given pieces have to come together to be successful.You''ve watched a lot of technology coming through, including at your new position at Mars. Which technology excites you?We all have to pay a lot of attention to CRISPR and the gene-editing technologies. There is certainly a number of intellectual property issues that have to get sorted out but that''s clearly an area that will have a huge impact not just on human health but on animal health and plant health as well.The other area I''ve been thinking a lot about lately is the microbiome. As sequencing technology has altered in cost and time, we have begun to be able to explore the microbiome in a way that historically was not possible. And it feels like we are moving towards a tipping point where the explosion of understanding is going to open up a lot of interesting opportunities for us to intervene. Whether that''s through traditional drug modalities or through altered nutrition or through changing the microbial community in soil to produce crops that have higher nutrient value or other approaches, I think that''s another broad area that seems poised to begin to offer really interesting results.Were you surprised that a company like Mars, which has not been a basic research company at all, is now giving you an opportunity to build something that is much more research-orientated?The reality of Mars is that they have actually had a very deep fundamental research program for a number of years. They got involved in the sequencing of the cacao genome and contributed it to the public domain, and they are now also involved in the sequencing of the genomes of a large number of orphan crops in Africa. So they have been very active in their research both in the company and in collaboration with academic scientists around the world. The nature of the company has meant that the work is perhaps not as obvious as others, but it is a remarkably science-driven company in much of what it does.You have done a myriad of things. What are the one or two things that you are most proud of?I am most proud of my efforts to keep a hand in both the commercial and the academic world. It certainly has not been easy but I have received enormous satisfaction from the opportunity to work with bright students at each of the schools I have had the opportunity to teach at. I am not sure there is anything more satisfying than the opportunity to work with students and feel you have helped them towards their goals.At the same time, I think I''ve been effective in doing that because I have managed to keep an active role in the applied world. In some ways, my greatest achievement has been finding a way to balance those two interests in a way that seems to have worked for the various organizations I''ve been affiliated with.How do you relax away from work? Do you have a family?I am married. My wife is a securities litigator so has a very active career of her own. We have two children, one in high school and one in middle school. I''ve had the privilege to coach both of them on their various soccer teams since they were each about 4 years old so that''s been a lot of fun.The other thing that many people will not find relaxing – but for some reason my family does – has been taking backcountry ski trips annually for a number of years. Worrying about navigating through the snow and finding shelter before darkness falls has a way of clearing the mind.     

Explain Bioinformatics to Your Grandmother!

What are you working on? You have certainly been asked that question many times, whether it be at a Saturday night party, during a discussion with your neighbors, or at a family gathering. Communicating with a lay audience about scientific subjects and making them attractive is a difficult task. But difficult or not, you will have to do it for many years, not only with your family and friends, but also with your colleagues and collaborators. So, better learn now! Although not usually taught, the ability to explain your work to others is an essential skill in science, where communication plays a key role. Using some examples of the French Regional Student Group activities, we discuss here (i) why it is important to have such communication skills, (ii) how you can get involved in these activities by using existing resources or working with people who have previous experience, and (iii) what you get out of this amazing experience. We aim to motivate you and provide you with tips and ideas to get involved in promoting scientific activities while getting all the benefits.     

How to choose a mentor

Mentors will play important roles in the careers of most successful scientists. Mentors are trusted advisors that give constructive criticism and provide information in many areas of a scientific life. Mentors will likely change throughout your career as your position changes and thus the areas of advice needed changes. Despite the fact that you gain new mentors, the relationships with the old mentors likely will continue and often grow into strong friendships. The American Physiological Society is a member of MentorNet, which is an award-winning, free, one-on-one electronic mentoring program for graduate students, postdoctoral fellows, and early career scientists who are APS members. Mentees and mentors are matched based on their responses to several questionnaires regarding research interests, mentoring needs, time needed, etc. Once assigned, mentors and mentees are allowed to approve their matches, and once done, contact information is given to each pair. A new mentor can be assigned every eight months. These electronic mentoring relationships are especially helpful if you are not comfortable discussing certain things with your thesis or postdoctoral advisor. APS encourages all members to participate either as a mentee or mentor in this valuable program. To comment on this article, go to http://www.the-aps.org/careers/ careers 1/mentor/mentoring.htm.     

Gaia Pigino: Inside the cell

Gaia Pigino studies the molecular mechanisms and principles of self-organization in cilia using 3D cryo-EM.

Gaia Pigino was only 3 yr old when she became fascinated with nature in the beautiful countryside of Siena, Italy, where she grew up. The neighbor’s daughter showed her a hen in the chicken coop, and they caught it in the act of laying an egg. Gaia remembers, “This was for me almost a shock, as my experience about eggs was that they come directly out of paper boxes!” Her father was also an important part of awakening Gaia’s curiosity for the amazing things in nature. He used to bring home the award-winning magazine Airone, the Italian equivalent of National Geographic. Gaia never missed an issue; even before learning to read, she could spend hours looking at the captivating photos of the wildlife. She wanted to understand what she was seeing, and maybe because of that, she was determined to do science.Gaia Pigino. Photo courtesy of Human Technopole.Gaia took her first “scientific” steps with Professor Fabio Bernini and Professor Claudio Leonzio at the University of Siena, where she studied bioindicators of soil contamination and detoxification strategies of soil arthropods as part of her PhD project. But it was later, when she joined the laboratory of Professor Pietro Lupetti and met Professor Joel Rosenbaum, a pioneer of cilia research, that Gaia discovered the world of 3D EM and felt her place was “inside a single cell.” She solidified her interest in the structure of protein complexes of cilia and flagella and boosted her passion for cryo-electron tomography (ET) in the laboratory of Professor Takashi Ishikawa, first at the ETH Zurich and then at the Paul Scherrer Institut in Switzerland. In 2012, Gaia started her own laboratory at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, with the vision of creating a truly interdisciplinary laboratory. Her team combines techniques from different fields such as biophysics, cell biology, and structural biology to answer open questions in the cilia field. Gaia recently moved countries again—this time to take over the position of Associate Head of the Structural Biology Research Centre, at the Human Technopole, Milan, Italy.We reached out to Gaia to learn more about her scientific journey and future research directions.What interested you about cilia?The first thing that attracted me toward cilia and flagella were some EM micrographs, by Professor Romano Dallai in Siena, that showed the beautiful geometrical microtubular structures of sperm flagella. I was intrigued by the apparent perfection of these organelles that clearly showed me that a cell is a coordinated system of complex molecular machines, the mechanism of many of which we do not understand. Soon after, Professor Joel Rosenbaum introduced me to the bidirectional transport of components inside cilia, which, he explained to me, is required for both assembly and function of virtually all cilia and flagella, from the motile cilia in our lungs to the primary cilium in our kidneys. He called it intraflagellar transport (IFT) and compared it to a Paternoster elevator, where the individual cabins were what we now call IFT trains. I was completely fascinated by the IFT system, the structure, the function, the dynamics, and the mechanism of which were still largely unknown. Quickly, I realized that in addition to IFT, cilia represent a virtually infinite source of open biological questions waiting to be solved, from the mechanics and regulation of the beating to the sensory function of primary cilia, and their importance for human health.What are some of the scientific questions currently of interest in your laboratory?In the past few years, we have made substantial contributions to the current understanding of the structure and the mechanism of the IFT (1, 2, 3). Currently, we are investigating how the structure of IFT trains relates to their functions by looking, in cryo-electron tomography, at how anterograde trains transform into retrograde trains and at how different ciliary cargoes are loaded on the trains. Beside this more classical line of research, we are exploring other approaches to study IFT, for instance we have developed a method to reactivate IFT trains in vitro on reconstituted microtubules. We want to use this approach to investigate the behavior of IFT trains, and their motors, in experimentally controllable conditions, e.g., in the presence of only certain tubulin posttranslational modifications. We have also made interesting discoveries about the distribution of tubulin posttranslational modifications on the microtubule doublets of the axoneme and how this spatially defined tubulin code affects the function of different ciliary components. We hope we will be able to share these new “stories” with the structural and cell biology community very soon!What kind of approach do you bring to your work?I believe that the main reason for why science became an integral, and dominant, part of my life is because it provides infinite riddles and continuous challenges. I have always been curious about how things work in nature, but I quickly realized that learning from books didn’t satisfy me. My desire was to be at the frontline, to be among the ones that see things happening in front of their eyes, at the microscope, for the first time. I wanted to be among the ones that make the discoveries that students read about in textbooks. Thus, what I bring to my work is an endless desire of solving biological riddles, curiosity, creativity, determination, and energy, with which I hope to inspire the members of my team. My laboratory uses an interdisciplinary approach; we use whatever method, technique or technology is needed to reach our goal, from the most basic tool to the most sophisticated cryo-electron microscope. And if the method we need does not yet exist, we try to invent it.A young Gaia Pigino (3 yr old) the day she discovered how eggs are made. Photo courtesy of Giancarlo Pigino.Could you tell us a bit about the Structural Biology Research Centre at the Human Technopole (HT)?At the HT Structural Biology Centre, we are working to create a vibrant and interdisciplinary scientific environment that will attract molecular, structural, cell, and computational biologists from all over the world. We are creating fantastic facilities, including one of the most well equipped and advanced electron microscopy facilities in Europe—and likely the world—headed by Paolo Swuec. My team, together with the teams of my colleague Alessandro Vannini and the research group leaders Ana Casañal, Francesca Coscia, and Philipp Erdmann, already cover a vast range of competences and know-how from classical molecular and structural biology approaches, such as crystallography and protein biophysics, to cryo-CLEM, cryo-FIB SEM and cryo-ET, all of which allow us to address questions in cell biology. Our goal is to create a scientific infrastructure and culture that will enable biologists to obtain a continuum of structural and functional information across scales.What did you learn during your PhD and postdoc that helped prepare you for being a group leader? What were you unprepared for?I learned that everyday research is mostly made of failures, but that with the right amount of obsession, persistence, curiosity, and creativity, it is always possible to succeed and discover new things. Being given the freedom to develop your own ideas and your own project very early in your career is a treat; science is not only about having good ideas! One needs to follow up on these ideas with intense work and troubleshooting to make them reality. In addition, I realized that being fearless and attempting what is considered too difficult by others, despite challenges, can turn into a worthy learning experience. Also, how you present your work to the scientific community matters for swinging the odds of success in your favor. Different places might work in very different ways, and conducting good science does not only depend on you, but also on the possibilities given to you by your environment.What was I unprepared for?—I guess several things, but one comes immediately to mind: I underestimated how much being responsible not only for my own life and career, but also the career of students, postdocs, and others in the laboratory, would affect me personally.Structure of the 96-nm axonemal repeat reconstructed by cryo-ET and subtomogram averaging. Image courtesy of Gonzalo Alvarez Viar, Pigino Lab.What has been the biggest accomplishment in your career so far?This is a tricky question for me... I tend to look into the future more than celebrating the past. I fight to succeed in something, but as soon as I conquer it, I find it less of an achievement than the thing I could conquer next. Nevertheless, I am happy about the discoveries and the papers published together with my students and postdocs (1, 2, 3, 4, 5). I am extremely excited about the fact that after many years of work I am now leading an interdisciplinary laboratory, where we combine techniques from different fields. I am also happy that three times my husband and I were able to move from one world class academic institution to the another to start exciting and fitting jobs and could still live together in the same place. We worked hard for this, but we also got lucky.What has been the biggest challenge in your career so far?I studied French in school; I had almost no exposure to spoken English until the end of my PhD. To avoid having to show my English insufficiencies, I did hide beside the board of my poster at the first international conference I attended in 2004! It took me a while to overcome this barrier and feel confident to express my thoughts and ideas in English.What do you think you would be if you were not a scientist?I had been a good fencer during my youth. I was a member of the Italian National Team between ages 14 and 19 and saw quite a bit of the world, which was cool! When my sporting career failed, due to diabetes, I was torn between art and science. I guess that in a parallel universe, I am a wildlife photographer and a potter specialized in wood kiln firing. [Gaia confesses that she misses “the amazing and addictive adrenaline rush of a good fencing match!”]Any tips for a successful research career?Do not compare your performances to the ones of the people at your career stage; compare yourself with people that are already successful one level higher than you currently are at. For example, if you are a PhD student, ask yourself what in your current performance separates you from being a good postdoc—once a postdoc, what is missing to be a good PI.     

Spinning plates and juggling balls

A PhD thesis is a project with an established goal and a deadline. As such, the tools, strategies and insight of professional project management can be used effectively to improve both research success and personal well-being.A project is a “temporary endeavour undertaken to create a unique product, service or result” [1]. Although this is a generic definition, it pretty much describes any PhD research project. There are many ways to manage a project effectively and efficiently. Unfortunately, most of us are so busy with our science that we forget about the importance of planning and management to our own success, sanity and health. Instead, we approach our first three years of genuine scientific endeavour wide-eyed and unprepared to juggle the hundreds of tiny balls that make up a PhD. Several techniques from the realm of ‘project management'' might therefore be helpful for PhD students who need to plan and manage the many competing demands that doctoral research can place on them.A PhD comprises both the research itself and the acquisition of skills and knowledge that will facilitate your future career. As such, it is of paramount importance to establish your own objectives early on. For example, alongside dividing your project into work packages—smaller projects that might be discrete or might build on each other—it is also essential to define which so-called transferable skills—additional knowledge and experience that might improve your job prospects—you feel will be of greatest use to you, depending on what you want to do after your PhD. The importance of these skills is becoming more widely recognized and taken far more seriously, and you should find that your supervisor is willing to give you the time to pursue them—your institute or university usually requires that he or she does so. More importantly, you should give yourself the time to invest in these skills, as they are going to be vital to everything you do once your PhD project is over.Doctoral research requires a multitude of skills, most of which you will inevitably lack when you commence your PhD programme. The first step is to identify the gaps in your knowledge to plan what skills on which to focus. This will allow you to acquire them in good time, either through professional activities—shadowing a postdoc, teaching undergraduates, joining journal clubs and blogging—or through both internal and external courses and workshops to improve communication, presentation, writing, networking and other skills. In addition to your planned skills acquisitions, you will also have situations arise, in which you need to acquire new skills quickly. The more you plan training activities and skills acquisition in advance, however, the smoother this aspect will be of your PhD. By way of example, part of my own PhD project relates to statistical analysis of data. An early analysis highlighted several areas in which I had to improve my skills, including hierarchical cluster analysis, principal component analysis and χ² testing against standard distributions. Having identified these gaps in knowledge early on in my doctoral programme, I could plan ahead accordingly when and how to acquire these skills.The full scope of your PhD project is usually unknown at the outset, and even the direction of your research might well change before you are finished. ‘Rolling wave planning'' is a technique that allows you to take these facts into account and plan the short-term future in detail, with a high-level provision for medium- to long-term activities. For those new to developing project schedules, I advocate a simple five-step approach. First, make an ordered list of high-level activities needed to achieve your goal. Second, expand this list by adding lower-level activities for which you have a detailed understanding of the scope, for example work to be performed in the next six months. You now have a work breakdown structure. Third, turn this work breakdown structure into a dependency-driven list by adding associations between the activities, for example by adding links to precursor activities that need to be completed before another activity can be started. Fourth, estimate the duration of each activity and extrapolate the start and end dates beginning with the first scheduled activity. Finally, as you progress through your research, and the scope of future activities becomes clearer, update the project schedule with these low-level activities as they become known. This approach of generating a hybrid-level project schedule, and updating with detailed activities as the scope becomes clearer, is known as ‘rolling wave planning''.…we approach our first three years of genuine scientific endeavour wide-eyed and unprepared to juggle the hundreds of tiny balls that make up a PhDThere is a range of professional software to help develop project schedules, but there are also various freeware tools available. Alternatively, you can use one of the many word processing or spreadsheet applications to make a simple Gantt chart. Along with the technical scope of your doctoral research, it would also be useful to include milestones that your institution enforces; for example literature review submission, formal progress reports and thesis chapter outlines. Including these in your rolling wave planning will allow you to keep in mind the bigger picture and the formal aspects that must be completed for your PhD, in parallel with the progress you are making towards your specific research subject.It is of course a cliché, but it is true that ‘failing to plan is planning to fail''. Of course the fluid nature of research makes it difficult to estimate accurately the time that it will take to complete various experiments, especially as a novice researcher. I therefore believe that although experiments do overrun and PhD projects can change, developing a project schedule is not a futile activity. By having a plan, even if it is made up of ‘guesstimates'', you can forecast roughly how much time you have left for your research and roughly what you can realistically hope to achieve. After all, without a plan, how can you predict when you will complete your research, submit your thesis and ultimately gain your PhD?Doctoral research requires a multitude of skills, most of which you will inevitably lack when you commence your PhD programmeThe serious consideration of scope is necessary in any project, but even more when you are simultaneously project manager, research scientist and key stakeholder. This raises various crucial questions regarding scope management: what is my doctoral research all about (the goal), and what work do I need to do to meet this goal? Once this has been agreed between you and your supervisor(s), it is essential to manage the scope of your project—the breadth and number of experiments you will perform—and how this will achieve your goal(s). Furthermore, be specific—knowing exactly what you want to achieve will keep you motivated until you get there.Project managers often use the concept of the triple constraint to manage work: scope, time and cost are intricately linked in a project and the different level of focus that each is given affects the perceived quality (by others) of project deliverables (Fig 1). Project managers understand that any deviation in one of the triple constraints changes one or both of the others. This is where the project schedule really comes into its own by allowing you to forecast when you will complete the agreed goals of your PhD project. For example, is your doctoral programme for a fixed-term period? If so, then once a project schedule has been agreed that uses all of the time available, any project overruns will cause an overrun to the overall PhD. The two main possibilities for a PhD student to manage this situation and bring the projected completion back into acceptable timescales are either to work longer or to reduce the scope or goals of the project, either by conducting fewer experiments to answer the same question or by modifying the depth of the question being asked. This leads to the issue of whether there is a minimum set of goals that need to be achieved, or whether several agreed activities are ‘nice to haves'', but are not crucial for the overall PhD. I believe that your supervisor(s) are best suited to answer questions about the minimum goals and the scope needed to achieve them.Open in a separate windowFigure 1The project management triangle as applied to a PhD. Three competing constraints influence project management: time, scope and cost. The time constraint reinforces that projects are temporary endeavours, and that in most cases have defined timescales (absolute deadlines). The cost constraint refers to the budgeted amount allocated to the project that, from the perspective of doctoral research students, will predominantly be focused on the amount and duration of the stipend awarded, but might also incorporate various expenses such as bench fees, conference fees and consumables. For those changing career, the cost might also comprise an element of salary sacrifice. The scope constraint refers to what must be done, produced or developed to meet the objective of the project, which in the case of a PhD generally comprises the actual doctoral research to be performed, development (and submission) of the thesis, publication of one or more journal articles, presentation at conferences and potentially teaching. The triple constraint principle highlights that any change to one of the constraints will have an impact on one or both of the other constraints. For example, increased scope typically leads to increased time and cost; tight time constraints usually mean that an overrun in activities (such as experimentation) might have a knock-on effect of requiring the scope to be reduced to submit your thesis on time, or increasing the overall amount of time required to complete your PhD. Similarly, a tight budget could mean you cannot gain access to various resources, resulting in either increased time or a reduction in scope. Recently, a fourth component of the project management triangle has been introduced highlighting that along with the three constraints competing with each other, they also interact to form a fourth dimension of quality.If you need to complete your doctoral programme within a specified time frame, then you need to manage your goals and scope mercilessly—do not allow additional research questions or extra experiments to take away precious time. This does not mean that you cannot deviate, but any deviations need to be managed. Remember, whether you wish to remain in scientific research or not, the PhD is a stepping-stone to your future career and not the end goal in itself. Once you have achieved the goals agreed with your supervisor, it is more beneficial for you to write-up your doctoral thesis and move on [2].Good communication is essential in every area of work, but even more so for a PhD as you are simultaneously learning how to research along with doing the research. Often, access to your supervisor is limited by constraints on his/her or your time, which means that clear communication is vital. Do not assume that your supervisor knows every intricate detail of what you are doing; he or she might have a large group in which each member is looking at complementary aspects of a more general topic. It is, therefore, your responsibility to ensure that all your stakeholders—supervisors, postdoc leads and any others involved—know what you are doing and, more importantly, why you are doing it.This is another area in which the apt use of technology can maximize efficiency. Subject to institutional licensing, collaboration tools such as SkillsForge or Evernote can improve communication between stakeholders. For example, meeting minutes, action points to be followed and research results can be uploaded for sharing. Supervisors can then review the material at a convenient time to ensure that they stay up to date with the progress of each student within their research group.As PhD students usually aspire to become research scientists, it is of paramount importance that you learn the correct application of the scientific method and the context in which your work is being done. Before jumping into practical work—wet-lab experiments or computational modelling—it is important to understand the meaning and relevance of your project in relation to existing knowledge and the underlying science. For example, the hypothesis-driven research life cycle in systems biology [3,4]—my own field—advises that computational models should be developed on the basis of wet-lab data relating to the underlying biological system. Almeida-Souza and Baets state that a PhD in science is an opportunity to learn how to tackle problems scientifically and, as such, requires the development of skills in critical thinking, hypothesis formulation and experimental design [5]. I believe that the requirement for these skills is universal across the sciences, and that molecular biosciences and computational systems biology are no different.The serious consideration of scope is necessary in any project, but even more when you are simultaneously project manager, research scientist and key stakeholderTherefore, before the first wet-lab experiment is performed, or the first line of code is written, it is essential that we understand why the experiment is important and what results we might expect to support our initial hypotheses. Furthermore, regarding computational systems biology, I believe that it is also essential for wet-lab and computational researchers to collaborate to ensure both have a consistent understanding of the data and the purpose of the computational model. After all, for the most part, computational models are developed for their predictive capacities and to allow hypothesis generation for subsequent wet-lab experimentation. Baxter et al have extensively covered this area and advocate not only designing the project up-front, but also the need for quality control [6].You need to manage the scope and goals of your PhD mercilessly and, at the same time, be flexible enough to grasp new opportunities. Conversations at conferences, for instance, can open up opportunities for collaboration and take your research in a direction that you had not considered previously. In my case, I was invited to turn a conference paper relating to my masters degree into a full paper for a special issue of a well-known bioinformatics journal. Although it was not related to my doctoral research, the prospect was too good to turn down. I therefore discussed the idea with my PhD supervisor, and once we were in agreement, I updated the project schedule to incorporate this new activity, trying to mitigate as much as possible the resulting slippages to my doctoral research. In essence, I had performed an impromptu risk–reward analysis and decided that the reward that would be gained from publishing this work outweighed the risk of a slight overrun of my PhD thesis. It must be noted that I was lucky in this instance, as my PhD supervisor also supervised the research project during my master''s degree, so a full paper would be beneficial for both of us.A project risk is “an uncertain event or condition, that if it occurs, has an effect on at least one project objective” [1]. The positive side to risks is that the likelihood of their future occurrence can be mitigated by planning in the present. Once a risk is realized, however, and its effects begin to be felt, it has turned into a project issue. The first step in trying to manage risks is their identification. Risk identification in this context is the process of determining which events, if they occurred, would affect your research. In the context of a molecular biosciences PhD, I believe that general risks relate to access to resources, such as people—postdocs and collaborators, for example—reagents, cell lines and shared equipment. For example, if your work uses fluorescent proteins within single cell analysis, how would you be affected if the fluorescence microscope was booked out by another research lab? Similarly, in computational systems biology, if the design process for your computational model requires access to wet-lab data, what would the effect(s) be if this was not available?Once risks are identified, it is important to develop risk response plans. By using the above example of access to a microscope, what should your response be if you cannot gain access? The initial risk response would be to liaise with the other research lab to understand their requirements and ascertain whether you could gain access at a mutually convenient time. Alternatively, another approach might be to work outside normal office hours, either throughout the evenings or on the weekend, subject to health and safety procedures at your institution and your own health and well-being. I believe that a degree of creativity is often required when developing effective risk response plans.A PhD thesis is a hefty document that might run to many hundreds of pages. They are generally not written as a single large document from start to finish, but as chapters. In the molecular biosciences, a thesis consists of an initial literature review early in the doctoral programme, work-in-progress documents for materials and methods, experimental results throughout the middle section, which is followed by analysis and critical evaluation towards the end of your experimental work. Whether through software tools or through your own manual methods, such as keeping a configuration log and keeping a copy of each version of your working documents, it is essential that you maintain an up-to-date repository of all your notes. I have found through experience that it is beneficial to save not only the final versions, but also each of the working drafts of documents generated throughout your PhD. Ideas previously discounted, and thus removed from more recent versions of documents, might once again take centre stage at a later date.The positive side to risks is that the likelihood of their future occurrence can be mitigated by planning in the presentThis can be aided through the development and use of a project library with a logical folder structure to facilitate easy access to documentation. Noble [7] provides an in-depth discussion of organizing your computational biology project—in particular the value of version control—but the concepts are transferable across disciplines. Furthermore, do not forget to back-up your work, and without seeming too pessimistic, back-up your back-up!Finally, look after the most important resource: you. Exercise, diet, alcohol, caffeine and holidays all affect your well-being. Holidays and time away from the lab or office allow you to take a step back from the detail and reflect on your experiences and progress. Sometimes, time off allows you to process issues subconsciously and develop new approaches to overcome problems that you have been tackling for extended periods of time without success. Finally, holidays also help you recharge your batteries and enthusiasm to return to your project with fresh vigour. If you have sensibly and reasonably planned time off alongside your work, you will be able to enjoy it.Although a PhD requires consistent commitment, you simply cannot—and should not—work at full capacity all of the time. Issues arise periodically throughout any project, and if you have no reserves of energy—either mental or physical—you will be unable to tackle them head on with the step change of performance that is required. Furthermore, doctoral research is a marathon and not a sprint; we all experience the symptoms of burnout from time to time, and sometimes it is better to walk away for a short period to recharge than to carry on, become stale, and ultimately slow down.To conclude, I wish you good luck with your doctoral research, and I hope these techniques help you to manage your PhD project through to successful completion.? Open in a separate windowRichard Alun Williams     

How to succeed in science: a concise guide for young biomedical scientists. Part I: taking the plunge

Biomedical research has never been more intellectually exciting or practically important to society. Ironically, pursuing a career as a biomedical scientist has never been more difficult. Here I provide unvarnished advice for young biomedical scientists on the difficulties that lie ahead and on how to find the right laboratories for training in the skills that you will need to succeed. Although my advice is geared towards succeeding in the United States, many aspects apply to other countries.     

Science funding and infrastructures in Europe

European science in crisis. Scared? Then read on; you should be. I argue that we cannot sit back for much longer and watch our best scientists emigrate to the USA for the most productive part of their career, and that European scientists should not tolerate a funding system that neither rewards an investigator's brilliance nor the innovative nature of their research. The EC Framework Programme is due for a face lift: scientists should wield the scalpel this time.     

Joan Heath interviews Suzanne Cory and Joan Steitz: a female perspective of science in the swinging ‘60s

Prompted by the occasion of International Women''s Day, Joan Heath and DMM reunited Professors Suzanne Cory and Joan Steitz via Zoom to discuss their extraordinary careers and joint experiences in science. They also delve into past and present challenges for women in science, and discuss the role of scientists in a post-pandemic world.

Suzanne Cory, Joan Steitz and Joan Heath (from left to right) As one of Australia''s most eminent molecular biologists, with a school in Melbourne bearing her name, Professor Suzanne Cory has been both Director of The Walter and Eliza Hall Institute of Medical Research in Australia (WEHI) and President of the Australian Academy of Science. She earned her PhD at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) in Cambridge, UK, with postdoctoral training at the University of Geneva. She continues her research at WEHI as an honorary distinguished research fellow, investigating the genetics of the immune system in the development of blood cancers and the effects of chemotherapeutic drugs on cancer cells.Joan Steitz – currently Sterling Professor of Molecular Biophysics and Biochemistry at Yale University, and for 35 years the recipient of a Howard Hughes fellowship – is best known for her seminal work in RNA biology. She was the first female graduate student to join the laboratory of James Watson at Harvard University and proceeded with her postdoctoral training at the MRC LMB in Cambridge. Her pioneering research delved into the fundamental mechanisms of ribosome and messenger RNA interactions, as well as RNA splicing, heralding the phenomenon of alternative RNA splicing. A recipient of many awards and honours, she is also involved in international projects aimed at supporting women in science.Host Joan Heath heads a laboratory at WEHI in Australia. She received her undergraduate degree from the University of Cambridge, followed by her PhD at the Strangeways Research Laboratory also in Cambridge, then just across the road from the MRC LMB. After postdoctoral positions in bone biology and osteoporosis research, Joan joined the Ludwig Institute for Cancer Research where she became a laboratory head, and changed her focus to cancer research using zebrafish to identify genes that are indispensable for the rapid growth and proliferation of cells during development. She joined the WEHI in 2012. There she showed that the same developmental genes are also required by highly proliferative, difficult-to-treat cancers, including lung, liver and stomach cancer, paving the way for translational research targeting these genes in novel cancer therapies. Joan H: How long have you two known each other? Suzanne: I was calculating that this morning and I was astonished because it seems like only yesterday, but it has been 55 years since we met in Cambridge. It has been a voyage in science and a voyage in the world because we have always made a point to meet up in beautiful places and go hiking. That is how we''ve been able to renew our friendship over all these years. Joan H: Where were you when you first met? Joan S: We both were working at the MRC LMB in Cambridge, England. Suzanne was doing her PhD and I arrived slightly later for a postdoc.Suzanne: We had a pre-meeting in the sense that Joan, Jerry Adams (my future husband) and Tom Steitz (Joan''s husband), were all graduate students together in Harvard. So, when Joan and Tom came to Cambridge, it was natural that we would all start doing things together. And Joan and I ended up sharing a lab bench.Joan S: The reason that I did a postdoc in the mecca of X-ray crystallography was that I had married a crystallographer – and there was no other place that he could possibly go. They very much wanted to have my husband at the Cambridge MRC lab, but there wasn''t a clear plan for me. Francis Crick suggested that I do a literature project in the library, but I knew that theory was not my forte in comparison to experiments. I started talking to the many people working in the lab and found a project that no one wanted, because it was so challenging. But it was a very interesting problem, so I decided to take it on – and it turned out to be a great project.Joan H: That''s amazing. You were obviously determined to overturn other people''s expectations of you.Suzanne, even now, it''s extremely unusual for a young person to leave their home country to do their PhD. It''s still a brave thing to do but all those years ago it was really courageous. You told me that you ended up there because you wrote a simple letter, which was a complete shot in the dark.Suzanne: It certainly was. During my master''s degree at the University of Melbourne, I became more and more interested in doing science and decided I would do a PhD. But I had a counteracting desire to travel and see Europe. So I decided that I would do my PhD overseas to give myself the opportunity of travelling. I had fallen in love with DNA during my undergraduate studies. So, I wrote a letter to Francis Crick in Cambridge, and asked if he would take me on as a PhD student. Much to my amazement, I eventually got a letter back saying yes. I think that my professor of biochemistry might have also visited Cambridge while he was travelling and spoken up for me. However, I was still extraordinarily fortunate that Francis had agreed because there weren''t many PhD students in the LMB at that time. It made such a difference to my entire life. I look back on that letter and think, “How did you have the audacity to write that letter and aim to go to that laboratory?”. I think it was partly naivety.Joan H: That''s a lesson for everyone, to go for your dreams, and don''t assume people won''t take notice of you. It is more difficult now, when scientists receive hundreds of e-mail applications from prospective PhD students in their inbox. You would have written a letter with a stamp on it that probably took three weeks to arrive, but it just shows you that you should be audacious. Did you have a different experience to Joan when you arrived? Was there a proper project already lined up for you?Suzanne: I was interviewed by Francis Crick and Sydney Brenner, who were the joint directors of the department. They decided that I would work on the structure of the methionyl-tRNA that puts methionine into internal positions in polypeptides. After they described the project – which involved doing counter-current distribution fractionation of bulk tRNAs, in which I had no experience whatsoever – Sydney in his very characteristic monotone said, “Do you think you''re up to it?”. I sort of gulped to myself and said, “Yes, I think I could do that”. I then went to Brian Clark''s laboratory, who was going to be my PhD supervisor, and started the project. Like always in life, if you learn from people and just go from one day to the next, you actually get there in the end.Joan H: So, persistence was key. Were there many other women at the LMB at the time?Suzanne: I don''t remember any female scientists who had official senior positions. There were certainly some strong female scientists there, but I don''t think they were given the recognition or the status that they actually deserved.Joan S: Later, some were given more recognition, crystallographers in particular, but not so much the molecular biologists.Suzanne: I think, as women, we both pioneered in that department.Joan H: Given the fact that you both agreed to take on projects you had very little previous experience with and that the male supervisors thought you weren''t going to have the mettle to carry it through, once you were there, did you feel that you had to work the whole time? Or did you still manage to have lots of fun and partake in opportunities that Cambridge had to offer at the time?Joan S: We certainly partook in a lot of those things. My husband and I got interested in antique furniture, antique paintings, and used to scour the countryside for little antique shops. We saw lots of England, then a little bit of Scotland and Wales. It was wonderful. A real adventure.Suzanne: I worked really hard most of the time that I was in Cambridge, as the work was very exciting. But I would take holiday periods, camping and youth hostelling all over Europe with a girlfriend from Melbourne and later, travelling with Jerry. We also would go to London for the opera and looking for amazing clothes on Carnaby Street and Chelsea Road (this was the Beatles era, late 60s). Jerry once came back with a purple velvet suit, which was his prized possession for many years. There was lots of fun but also lots of work.Open in a separate windowJoan Steitz, Tom Steitz, Jerry Adams and Suzanne Cory (from left to right) in the Swiss Alps, 1970. Image courtesy of Mark Bretscher. This image in not reproduced under the terms of the Creative Commons Attribution 2.0 Generic license. For permission to reproduce, contact the DMM Editorial office. Joan H: Can you remember the first moment in that part of your career that gave you the most pleasure? Joan S: I worked on a project for about a year, and it turned out that I was doing the wrong fractionation method to get the material that I needed to analyse. Then I had a conversation with Sydney Brenner telling him that I was going to give this one more try with a new method, and then I was going to give up. I remember Sydney saying, “Sometimes, like with a bad marriage, you have to give experiments one last try before you give them up.” Then I tried again, and it worked. This is often the case in science, that you try something new, that''s a little bit different, and it makes all the difference. Then you''re running.Suzanne: The same thing happened to me. I was labouring away on the counter current distribution machines fractionating methionine tRNA, with the goal of sequencing it by the laborious procedure recently published by Robert Holley. However, Fred Sanger, in the department upstairs, had invented a totally new method for sequencing using ³²P-labelled RNA. I desperately wanted to try this, so I managed to persuade my supervisor that we should change techniques. That change was key to my future because the approach was successful. I still remember to this day exactly where I was in Cambridge, walking on a Sunday afternoon, when the last piece of the puzzle dropped into place in my mind, and I had the entire sequence. In that moment, I was extremely joyful, because I knew I had my PhD and that I had succeeded. So that was my eureka moment.Joan H: Obviously, these were extremely productive years, and you''ve mentioned several Nobel Prize winners in your midst. It must have been the most inspiring environment, which I''m sure had a big impact on what you did next. By this stage in your career, were you already feeling ambitious or was it still your scientific curiosity that was driving your path?

“I expected that I would go back to the United States and be a research associate in some man''s lab […]. Then it turned out that people were more impressed than I thought and started offering me junior faculty jobs.”

Joan S: I had gotten a lot of recognition for having sequenced a piece of mRNA, using the same methods that Suzanne used to sequence tRNA. However, I had no expectations, because I had never seen a woman as a science professor, or head of a lab. I expected that I would go back to the United States and be a research associate in some man''s lab, and maybe they''d let me guide a graduate student. Then it turned out that people were more impressed than I thought and started offering me junior faculty jobs.My husband had already secured a junior faculty job in Berkeley before we even went to England, so we went back there after two years. My husband went to the chair of the department in Berkeley and put down letters on his desk of job offers that both of us had received for independent, junior faculty positions from several universities. The Chairman then said to Tom, “But all of our wives are research associates in our labs, and they love it”. This tore at my pride, as there had been a couple of universities that offered us both faculty jobs, and Berkeley was only offering one. So, we didn''t stay at Berkeley, and we came to Yale, which was wonderful.Suzanne: It''s really amazing to think that they gave you up. How foolish they were.Joan H: They''ve lived to regret it a million times over. Suzanne, at that point were you ready to climb this very difficult ladder?Suzanne: Like Joan, I didn''t have any expectations. For me, it was a matter of being able to continue discovering things in science. Jerry had already arranged to start a postdoc in Geneva. So, I applied for a postdoctoral fellowship, and obtained one. We went off together to Geneva to start our married life, and that was the beginning of us doing science together, which we''ve done ever since. I think without Jerry guiding me at that stage in my life, I would have probably drifted out of science. I don''t think I had the scientific confidence to ever think that I would be running a lab. For me, it was just continuing a voyage of discovery; and being lucky to end up in a wonderful scientific partnership and, through that partnership, my confidence grew over the years. Joan H: How many years after your postdoctoral training was it before you looked around your environment and had the confidence to think that you could be a lab or department head or could run an Institute? Joan S: I would say that confidence just grew. Tom and I were part of a departmental overhaul that involved hiring about six new people at Yale. We all stuck together, supported each other and were very collegial even though we worked in different areas. I think the collegial nature of the department in Yale helped me gain confidence. It was very scary at first because I didn''t know if I could write grants or direct people.Suzanne: Cambridge had an incredible influence, certainly over me, and I''m sure over Joan, Tom and Jerry, too. We looked around and saw all these amazing Nobel laureates, but also all these very ambitious, talented postdocs from around the world. I don''t think anyone thought about being the head of a department at that stage. We were simply striving to make discoveries and we gave each other mutual confidence, and stiff competition, too.The other thing that Cambridge gave us, was a new technology. For Joan and me, it was RNA sequencing. Being able to do that technology opened doors all around the world. I now always advise young people to go to the best place in the world to train in your chosen subject and acquire a new technology, because that will open the door to many opportunities in the future.Jerry and I made some excellent discoveries in Geneva, which were published in front-rank journals. Then it was time to move to full independence. I really wanted to go back to Australia but, as Jerry is an American, it was not at all obvious that he should take the big leap of moving to the bottom of the world and starting a lab there. I owe him a tremendous debt because he decided that he would take that risk.Earlier, whilst on our honeymoon, we had visited various labs in Australia. Although WEHI was an institute for immunology, a field we knew little about at that stage, it had the same atmosphere as the LMB in the sense that everyone was striving at the frontiers of science and competing with the rest of the world. We decided this was the only place in Australia that we would work at and that we would attempt to persuade the new director Gus Nossal that he needed molecular biologists. We had an interview with him in Switzerland and he offered us jobs as postdocs. Again, we were probably very naive and audacious but we told him we didn''t want to be postdocs – we wanted to run our own lab. And he agreed and we launched our fledgling lab together in 1971. What drove us was always discovery, rather than career ambitions.Joan H: You''ve both described these amazing sets of circumstances that were challenging but, nevertheless, very satisfying. However, a lot of things have since changed. What do you think are the main remaining barriers to women in science?Joan S: There is an important phenomenon called social identity threat, or stereotype threat, that I think still impedes women in proceeding in their careers. The phenomenon is described by cognitive psychologists as a reaction that all people experience if they feel that they are part of an undervalued minority. And so, by definition, since there are fewer women in science than there are men, women are being subjected to stereotype threat. Cognitive psychologists have studied the physiological manifestations of this, including increased heart rate and perspiration but, psychologically, they''ve also documented that cognitive learning and memory are impaired when one has these feelings.I first learned about this in 2007 and I looked back and realized why, for 30 years, when I''d been on committees as the only woman amongst ten men, I wouldn''t dare say anything – because I was frightened stiff. Men undergo this response, too, if they''re put into the situation of being undervalued. If you understand why you''re reacting the way you''re reacting and know that this is a normal human response, I think it helps you to overcome your own feelings of insecurity and allows you to go ahead. I always tell young women who I''m rooting for in science about this, because I want them to know that they will very likely end up feeling this way, and it''s a normal human response.

“One thing I sometimes get frustrated about is that we often need men to change things […] but what we really need are women in those high-level positions, so that they can be the champions of change.”

Joan H: There are other terms describing other relevant phenomena, such as unconscious bias, imposter syndrome and champions of change. One thing I really relate to is imposter syndrome. I''ve listened to webinars on this topic and they all reach a similar conclusion that we all feel the same. On the one hand, at the end of the webinar, you do feel somewhat elated to know that it''s not just you, and that it''s normal. But, on the other hand, it doesn''t really change things. It''s a recognition of what we feel, and we all get some help from that, but you really need opportunities to change things at a higher level. One thing I sometimes get frustrated about is that we often need men to change things, leading to this concept of male champions of change. I admire those men; but what we really need are women in those high-level positions, so that they can be the champions of change. Not having 50% of university departments and medical research institutes run by women still limits our full potential.Joan S: I certainly agree with you, Joan. It''s very important to have realistic role models. Suzanne being head of the WEHI for all those years has engendered all sorts of admiration.Joan H: During that period, Suzanne not only did fantastic science but our Institute doubled in size.It''s transformative when you have women making up 50% of people around the table. It''s no help just having a token female because that poor person''s not going to be able to change everything on her own. In American scientific institutions, are there any firm quotas for female scientists and other people that are underrepresented in science?Joan S: In recent years there has been a push in that direction. Sometimes it''s successful and sometimes it''s not. It is very different now compared to when there was no consciousness that this was unfair or that things could be better if we had real representation.Suzanne: I agree with both of you in everything that''s been said. While reflecting at this moment, what it says to me is that what''s really needed is societal change, and that we need to give courage to girls from the very earliest age. It should come naturally, they shouldn''t feel inferior, and others should not look at them as inferior. They should expect to have careers as well as families, be able to manage both and have somebody alongside them who helps them manage both.I think that affirmative action for women in science is necessary because the pace of change has been so slow. However, I also think quotas can be detrimental to the cause of women, in the sense that it''s then possible for people to say you only made it because there was a quota – which is very destructive. If I look back on our careers in science, it is clear that things have changed tremendously. Today there are more opportunities for women because many universities and institutes are bending over backwards to equalise things. The downside of this is that talented men may miss out on positions because of this policy and the pendulum could swing back.Joan H: The evidence shows that when more women are involved in things, those things go better. For instance, boards that have more women on them are more productive. Obviously, what you alluded to is there are lots of fantastic male scientists as well. The real issue here is there''s not enough funding to go round to support all the great men and women. But there are clearly enough good women around to be represented at the 50% level, without disproportionately disadvantaging male scientists.Joan S: Men and women are now operating on a more even playing field, which doesn''t mean that the men are missing out. They''re just in a more-competitive situation – as they should be. Joan H: Suzanne previously covered the specific advice she would give to young female researchers. Joan, do you have any other suggestions? Joan S: I encourage them to try lots of different things in science, and when they find something that really grabs them, then go for it and be persistent. We all know that science is very up and down. But if you keep pushing when you''re in a trough, it will always go back up again and you will succeed. That''s harder for a young person, who hasn''t experienced these troughs, to understand.Joan H: Yes, and the period when women scientists start having children is the hardest part. It''s still a choice that some women make, to take some years off and come back with a less ambitious plan for their career. Obviously, things like maternity leave payments and so on are improving but there''s no question that, in most circumstances, the research will slow down during that period.Suzanne: What I say to young women at that stage of their careers is that you have to be very focused, you must spend the time that you do have in a very focused manner, so that you can be the most productive you can be. But you have to be supported at home by your partner. If you''re both scientists it''s easier because you can appreciate why the other person is rushing into the lab late at night, for example, but for most people, that''s not true. So, what is really important is equal sharing of responsibilities from both partners when young families are around. And I think employers need to give both of those partners a longer time to achieve the kind of papers that they need to progress in their careers. That''s a period when it is much harder to be productive, and we need to continue to support people during that difficult phase of their careers because we''ve invested so much in them. They have so much to offer to science and to society, so to let them slip out at that stage is a great waste.Joan H: Let''s change tack a little bit and think about some of the broader challenges in science. What do you think the COVID-19 pandemic has taught us about the importance of clear scientific communication and real engagement with the community?Joan S: Whenever I talk to people about this, I very clearly make the point that it was decades of fundamental research that led to the development of the COVID-19 vaccine. If it hadn''t been for those fundamental discoveries in how cells and mRNA work, it would never have only taken 63 days from sequencing the virus to phase one clinical trials at Moderna. I try to point out to people that all the different discoveries coming in from different angles made that possible. I personally find it absolutely remarkable that all that knowledge could be harnessed, so very quickly. I''ve been doing fundamental research my entire life and I never expected to see it materialise in the way it has. It''s a wonderful reward. Joan H: Do you think this has resulted in the community appreciating scientists more? Joan S: I don''t think we''re far enough downstream to know that. In the US, there has been a congressional vote to abandon our maintenance of vigilance and preparedness for future pandemics – which seems ridiculous. Now we have all these procedures set up, all we have to do is maintain them for the next one. Whereas, if we just let go of these procedures, we''ll have to start over again for future pandemics. I guess we''re not good enough at communicating some of these things at this point.Joan H: Millions of people died from the virus and yet, if we hadn''t had the vaccines, the scale would have been even more horrific. If we were able to convey this information effectively to the public, then, hopefully, people would recognise that – as well as spending a fixed percentage of the gross domestic product on defence, for example – we should spend at least the same amount on science. Not only for pandemics but for tackling climate change and other pressing issues. I like to think this is an auspicious time but I don''t know whether we are really taking advantage of it.Suzanne: The pandemic has brought science and scientists to the forefront, and there has been a period of great respect for scientists having developed the vaccine. It''s an absolute miracle that it was done so fast and effectively. We''re very fortunate but, as Joan said, that was not luck. It was through investment in basic science for decades. We have to keep conveying this message, to our politicians in particular, so that they will keep supporting all kinds of scientists, because we never know what''s around the corner.Joan H: Certainly, people like Anthony Fauci in the US and Catherine Bennett in Melbourne, spoke eloquently and had a real talent for communicating things clearly and in a nutshell. That''s not something we''re all good at and it''s not something that is easy to train into people either. I think we all need to try to capture the attention of the community at large, by speaking plainly. I don''t think people understand that scientists are underfunded and could do so much more if funding was more generous.

“All I can say to young people is, if you really love science and have a passion for it, keep trying – because you will succeed if you put your whole heart and soul into this career path.”

Suzanne: I think the general public has no appreciation of how tenuous the life of a scientist can be, and how we are losing so many great minds entering the field because young people just finishing their PhDs look with dismay at how hard it is to support a career in science and get enough funding. There''s a tremendous waste of talent. All I can say to young people is, if you really love science and have a passion for it, keep trying – because you will succeed if you put your whole heart and soul into this career path.Joan H: This has been an absolutely fantastic discussion and it''s such a delight to talk to women who, after all these years, are still as passionate as ever and are pursuing their scientific subjects with the same vigour as they have all along.Suzanne: It''s been wonderful to talk with you, Joan, and I hope that we see each other soon, no matter what continent. And thank you, Joan Heath for getting us together and giving us this opportunity.     

Organizing a PhD symposium—an inside view

Planning a symposium organized by PhD students is a challenging prospect. Insight from the organizers of three such symposia sheds light on the highs and lows of the experience.When we took on the responsibility for our respective annual PhD symposia (Sidebar A), none of us had any idea how much we would have to learn about organization, management and logistics; how many e-mails would be sent; how many deadlines missed. In the end, however, organizing a PhD symposium was in many ways the most instructive part of our first year as PhD students. We had the opportunity to meet and speak with brilliant scientists and we learnt how to coordinate, plan and execute different tasks efficiently with a good team spirit. Both the contacts we made and the skills we acquired should prove useful in our future careers. If you have the opportunity to get involved in organizing a symposium, we hope our experience will help you in making a start.

Sidebar A | The conferences we organized

The 3rd PhD Symposium in Computational Biology and Innovation hosted at the Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland (5–7 December 2012).The 14th European Molecular Biology Laboratory (EMBL) PhD Symposium hosted at EMBL campus in Heidelberg, Germany (24–27 October 2012).The 8th FinBioNet PhD Symposium: Revolutionary bioscience: from advanced technologies to personalized medicine hosted at the University of Tampere, Finland (2–3 October 2012).Perhaps more than any other kind of meeting, a PhD symposium is a great opportunity for early-stage researchers to be exposed to a broad range of science and to meet fellow PhD students and potential collaborators in a friendly atmosphere. By organizing one, you will contribute both to your own career and to those of everyone involved. Many university graduate programmes and societies encourage the organization of such events.If you have the opportunity to get involved in organizing a symposium, we hope our experience will help you in making a startThe amount of work involved, however, is huge and requires the coordination and cooperation of a committee. Your first step, then, is to recruit that committee. An announcement to pique the interest of local PhD students is a good idea to get started, followed by the cooption of members from different areas, groups and institutes to improve diversity and broaden the committee''s knowledge. It also helps to divide the committee into different teams, and to elect a chair, vice-chair and team leaders to keep things on track. Defining clear responsibilities and setting deadlines is vital, but keep in mind that you will need to be flexible, as committee members might find they have more or less time than they planned. In addition to research, both internships and placements are common during the early phases of a PhD and you might unexpectedly lose core committee members along the way. In our case, losing a committee chair meant that the vice-chair had to take over most of the coordination and invest more time during his or her absence.In general, keep in mind that the people you are working with are not full-time employees. It is unlikely that anyone on the organizing committee has done something similar to this before, and so time must be set aside to bring people on board and get them up to speed. Some of your committee members will prove capable of working independently and will require little management; others might be overwhelmed by the demands of their research and will require assistance and micromanagement.In addition to research, internships and placements are common during the early phases of a PhD and you might unexpectedly lose core committee members…You therefore need to monitor people and be prepared for setbacks. As you will collectively bear responsibility for the symposium, work left undone will often fall to other committee members or to you if you are the chair or vice-chair. Just how much slack you have to pick up will depend on your management skills. As long as you have a plan and a clear overview of what needs to be done, management should be straightforward, if not always easy. A well-managed symposium will be a pleasure to organize. A poorly managed one will become a stressful and unpleasant experience.Dividing the labour correctly is the first crucial step. This should happen as early as possible. Sidebar B lists important categories of tasks that must be managed. Large areas—finance, participants and speakers—will probably need sub-committees of their own, while smaller areas such as website management and design might need only one or two people. A large symposium might require a team of 12 people for speakers alone, with one assigned to each speaker. Ideally you will have previous symposia hosted at your institution to use as a blueprint. If not, contact another institute and ask them for an outline. Above all, each task must have a committee member clearly responsible for it, as ambiguous instructions and diffusion of responsibility will result in inaction. Predicting how much work will be involved is difficult, and it is all too easy to under-estimate, leaving you understaffed on the day of the event. Too many staff is far better than too few, and you will find that the ability to be flexible and reassign people to tricky areas or problems is vital to your success.

Sidebar B | Important committee tasks

Speakers—contacting speakers, soliciting abstracts and direct assistance to speakersParticipants—selecting plenary speakers and editing abstracts for the abstract bookFinance—fundraising and book-keepingPR—marketing through e-mails and posters, and securing sponsorsPosters—organizing posters on the day and judging any competitionsCatering—providing food and refreshmentsDesign—designing abstract booklets, posters and logosTransport and accommodation—arranging transport and accommodation for speakers (and participants)Website management—ensuring that the website is updated regularly with information about speakers, sessions and travelWithout the right content—speakers, topics and networking opportunities—no symposium will succeed, whether it is organized by PhD students or seasoned professionals. With a committee formed, the most important task is to decide on a scientific theme and a title for the symposium. It is always good to seek suggestions from your peers and mentors, especially because this will raise awareness that the symposium is going to take place. How you ultimately settle on a theme is down to you, but a voting system might be helpful. Remember, however, that the people organizing the symposium need to be confident in its direction and vision. Once a theme is chosen, the next step should be to set the number of sessions and agree on topics for each of these sessions (Sidebar C).

Sidebar C | Deciding on a topic and title for your symposium

• The subject of the symposium should be broader than most academic conferences.You want to avoid competing directly with specialized conferences, and instead appeal to a broad range of PhD students.
• Avoid being vague—at the same time, it is vital that a PhD student in any field will read your poster and think ‘this conference is for me''. Moreover, they will need to be able to convince their group leader of it as well.
• Be aware of competitors—the topics of the symposium should not overlap with symposia that are going to be held around the same time.

Once you have settled on your theme (or themes) and set a date—keep in mind the dates of other symposiums and any public holidays—you need to begin recruiting speakers. Invitations can be sent out by e-mail and should be followed up after a week or so either by e-mail or, preferably, by telephone. Be audacious in inviting speakers—we were often surprised how willing top-tier speakers were to attend specifically because we were organizing a PhD symposium. There are two advantages for them in attending these kinds of events: the atmosphere tends to be more relaxed than other prestigious conferences, and senior attendees can interact with and influence the emerging generation of scientists. Therefore, be confident to select and invite high-profile speakers first. They will usually have personal assistants who respond to their e-mails and invitations and manage their busy schedules. Remember that you will probably receive several rejections, so take these in your stride. You can also ask the speakers to suggest the names of other suitable people to invite. Bear in mind that good speakers tend to run on extremely tight schedules, so they need to be contacted early. They should not be expected to stick to the first deadline given, or the second, or any other deadline. They will also need to be reminded gently every now and then to send their abstracts and other information. Do not be afraid to use connections you might have for ideas and information on speakers: professors, admins, old supervisors and industry contacts will all probably help in finding people and getting them to say yes.When choosing a keynote speaker, young principal investigators and accomplished post-doctoral fellows are also excellent choices. Young investigators have often achieved success by advocating new or controversial ideas and methodologies, and their presence at a symposium can enliven debate. They can also offer advice to students more immediately relevant to success in today''s scientific climate. In this vein, it is beneficial to have speakers from different stages of their scientific careers to provide a variety of perspectives in discussions.It is a good idea to have a backup plan with a small list of local and national speakers for each session in case a speaker cancels at the last minute. In all three of the symposia that the authors were variously involved in organizing (Sidebar A), there were last minute difficulties or cancellations. For example, last minute travel changes might be too expensive for your budget to cover, or planned travel might not work out as a result of weather conditions or illness.The risk with a back-up plan, of course, is that you might end up with too many speakers and find yourself in the embarrassing position of having invited someone and not actually needing them. There is no simple answer to this, but try to have a good personal relationship with your backup speakers and be upfront with them about the circumstances in which you are inviting them.Finally, PhD student symposia should be a platform for students to acquire knowledge and present their work, so make sure you include poster sessions and student presentations. They are also an important opportunity for your peers to impress future employers, make contacts and gain insight into the ‘hot'' research areas and future opportunities. Student talks can be chosen from among the submitted abstracts.With your topic chosen, teams defined, organizers recruited and speakers selected, the real work of planning sessions, sorting out speaker invites and travel, arranging catering and so on will begin (see the timeline depicted in Fig 1). It is important to start planning early—up to a year in advance—but as every good manager knows, long-term goals will be forgotten, so short-term goals are crucial to success. Three weeks is a good rule of thumb for the maximum length of time you can set for a deadline. The whole committee should have a shared checklist of everything that needs to be done, when and by whom. You should have a clear record of who has agreed to what responsibilities and everyone should know whose job it is to chase things up if deadlines are missed. This should be enough to ensure that the work gets done. If someone seems incapable or unwilling, then simply transfer his or her responsibility to someone else.Open in a separate windowFigure 1Timeline of symposium organization.Regular meetings will allow you to check in on each committee member and will facilitate communication more effectively than e-mail. Video-conferencing will need to be well-coordinated if it is to work. Distribute an agenda before each meeting and stick to it. Minutes should also be taken during each meeting and distributed afterwards by e-mail. Above all, make sure that the various teams are communicating—ask your committee members what they are doing and what information or help they need to get it done. Special care should be taken to ensure communication if committee members are geographically separated.Predicting how much work will be involved is difficult, and it is all too easy to under-estimate, leaving you understaffed on the day of the eventThe success of your symposium will be measured in a few ways. The most obvious and important will be the quality of the talks, the networking opportunities provided and whether or not the attendees had an enjoyable and interesting time. However, you will also be judged on your finances, so you need to have a clear view of how much you can spend. Handling such large amounts of money can be intimidating, so keeping good records and staying on top of things is the only way to feel comfortable about doing this and coming out the other side.The money you obtain from fundraising, sponsorship and grant applications cannot be accurately assessed early on, but you should account for it as best as you can. If you have the luxury of blueprints from previous symposia, get hold of their final budgets for guidelines on general expenses such as food, advertisement and printing (see Fig 2 for the example of our experience).Open in a separate windowFigure 2Financial breakdown of our symposia. Two different types of symposium are represented. The ‘Example income breakdown'' and ‘Example expenses breakdown 1'' are based on the example of the University College Dublin Symposium, the funding for which was external (grants, sponsorships and registration fees). ‘Example expenses breakdown 2'' is from the FinBioNet Symposium, which is supported by several doctoral programmes in Finland and, thus, grad students from participating programmes in Finland can attend free of charge. As such, it includes full payment of accommodation for speakers and attendees, and is a special case—a 50/50 split between flights and hotels is unusual for a symposium. An important message in the charts is that catering will probably take up half of the expenses of a symposium, and keynotes and speakers probably around a quarter.The attendance fees you will receive can deviate significantly from your projected numbers. This can be mitigated to some extent by early registration deadlines with discounts to encourage the majority of your attendees to register as soon as possible, as well as an easy and efficient payment system and interesting keynote speakers. Regular discussions of the budget are also crucial to keep on top of things.In terms of raising other money, consider submitting grant applications to as many societies, universities, trusts or foundations as possible. They will have a fixed timeframe in which you can apply for grants: for example, 3–6 months in advance for smaller grants and more than 6 months in advance for substantial sponsorship. It is important to have confirmations from invited speakers and estimates of attendance numbers before applying for grants.To save money, it is also beneficial to book the flights and hotel accommodation for invited speakers well in advance, rather than leaving it to them. The organizers of the PhD symposium held in 2012 at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, for example, were able to cut down the transport costs of their speakers by more than half compared with the previous year simply by booking in advance and using budget airlines. Flights within Europe with the wrong non-budget airlines can cost as much as three or four times more. If the invited speakers are left to choose their own flights, the budget for speaker travel might be bigger than expected.Commercial sponsorship will also help you balance your books. When approaching sponsors, aim for a mix of sponsorship levels and offers. Do not ignore the small sponsors, but make sure that you provide the right opportunities for the big ones to pay extra for certain privileges. A large sponsor could be the essential cash injection that your symposium needs to get a brilliant keynote speaker flown in from the USA, or food that actually tastes as good as it looks.If you are lucky, your predecessors will have been able to secure one or more big companies for sponsorship in previous years, so be sure to use the contacts that you already have. If the representatives liked your event, they will probably recommend it internally. Big companies also tend to give more non-money items. Offer them the opportunity to sponsor prizes or provide items for the conference bags. Even gaming-related companies will readily provide you with gadgets if you can manage to get them interested or tie one of their products to your symposium. Smaller companies will not have a big yearly budget to fund events, but if your symposium has a specific focus, contacting related companies close to your city might give you a greater chance of getting them interested.…the atmosphere tends to be more relaxed than other prestigious conferences, and senior attendees can interact with and influence the emerging generation of scientistsIn general, you need to keep your sponsors happy. They need to have a place to interact with your attendees, a booth for product advertising and a short presentation during the symposium. For smaller symposia, it might also be better to arrange specific sponsorship deals directly with a company, rather than relying on trying to block sell traditional tiered sponsorship—silver, gold and platinum levels. For the PhD Symposium in Computational Biology and Innovation in Dublin for example, Logitech agreed to donate three of their high quality wireless presenters that we could give away as prizes. Always keep in mind that global companies often have small departments that have useful gadgets which can be used as prizes or give-aways.Spreading the word is one of the most important steps in planning your symposium and should be started as early as possible. You should have a conference website that provides information and regular updates about your event. An eye-catching logo tied to the scientific topic also helps. Social networks—especially Facebook and Twitter—and e-mails make it extremely easy to reach interested researchers and PhD students.If your scientific field has an active international society, you should apply for an affiliation. The affiliation can be purely to help with promotion, but financial sponsorship is also possible in some cases and can open the door to more advanced grant applications that require an affiliation with a scientific society.Bear in mind that advertising your symposium too early can mean that interest might wane by the time that registration opens, whilst advertising too late might mean attendees have already made other plans. A good strategy is to spread the word once the date, venue and the first invited speakers have been confirmed. Follow this up by bursts of advertisements just before you open up registration and abstract submission. Most focused research communities have dedicated mailing lists—either regional or international—that will reach a substantial group of interested researchers. Contacting supervisors or programme directors in various universities who have students in a similar field is also a good idea. Ask them to forward your advertisement e-mail to mailing lists or PhD programmes they might know of. Generally, social or viral advertisement is free of charge and can reach far more people than any other medium.On the day itself, organization and a clear division of labour will be doubly important, so if you have already established good communication and working practices in the planning stages, this will pay dividends. If possible, have backup committee members ready to fill in for important tasks. Pay particular attention to speakers and sponsors: you have the reputation of your institute to consider. If possible, each speaker should have an assigned committee member. Make sure that each person knows exactly what he or she is supposed to be doing and leave enough time to account for delays. It is a good idea to do some practice runs before the event itself, as you will not have much time on the day to accommodate major changes. Things you might want to consider include: are there enough signs that direct you from the bus stop to the right building? Is it clear what opportunities there are for social events? What else will participants need? Hopefully you will already have considered these questions when people registered and will have captured much of the information on the registration forms. Similarly, you should have asked attendees to provide the kind of information you will need to know in advance about their dietary needs, disabled access needs and so on.PhD student symposia should be a platform for students […] so make sure you include poster sessions and student presentationsRemember that you are really doing this for the participants. Although the lectures and speakers are important, they are a part of the bigger picture of poster presentations, networking and PhD student talks, which are all equally important. The best conversation starters are social events, so take the keynote speakers out to a pub and invite everyone to join, or organize a dinner for everybody. Formal dinners are nice for large conferences, but a small PhD symposium greatly benefits from its informal environment. The first night, especially, can be a great chance to use for networking and social outings.Once the final talks are finished and the prizes are given, make sure you thank everyone: speakers, attendees, sponsors and supporters, and last but not least, yourselves, the organizing committee. Taking feedback from attendees is important, but it can be equally important to provide your own feedback for the group of PhD students who will organize the symposium next year. If you are part of a recurring event, you have a responsibility to them and should keep good records and be ready to advise them when they need it.Finally, we would recommend treating yourselves to committee t-shirts or hoodies so that you are easily identifiable to the multitude of people who will have questions for you or will need your help on the day. And so that you have a souvenir of all the hard work you put in. Good luck!     

Ten simple rules for finding and selecting R packages

R is an increasingly preferred software environment for data analytics and statistical computing among scientists and practitioners. Packages markedly extend R’s utility and ameliorate inefficient solutions to data science problems. We outline 10 simple rules for finding relevant packages and determining which package is best for your desired use. We begin in Rule 1 with tips on how to consider your purpose, which will guide your search to follow, where, in Rule 2, you’ll learn best practices for finding and collecting options. Rules 3 and 4 will help you navigate packages’ profiles and explore the extent of their online resources, so that you can be confident in the quality of the package you choose and assured that you’ll be able to access support. In Rules 5 and 6, you’ll become familiar with how the R Community evaluates packages and learn how to assess the popularity and utility of packages for yourself. Rules 7 and 8 will teach you how to investigate and track package development processes, so you can further evaluate their merit. We end in Rules 9 and 10 with more hands-on approaches, which involve digging into package code.     

Hongyuan Yang: Tracking lipids,one droplet at a time

Hongyuan Yang investigates lipid trafficking and lipid droplet biogenesis.

Hongyuan Yang grew up in a small city east of Beijing, China. From his childhood, Hongyuan recalls that “food was not abundant, so I was hungry at times, but education was free and good.” Driven by his curiosity for science, after completing his undergraduate studies at Peking University Health Science Center, China, he enrolled at Columbia University, NY, for his doctoral training. Under the guidance of his advisor, Dr. Stephen Sturley, Hongyuan studied lipids in budding yeast. The laboratory’s research department fostered a strong interest in lipids and atherosclerosis, and after earning his PhD, Hongyuan obtained a faculty position at the National University of Singapore (NUS) in 1999. In 2007, he moved to the University of New South Wales (UNSW) in Sydney, Australia, to continue his scientific journey exploring lipids. We contacted Hongyuan to learn more about his career and interests.Hongyuan Robert Yang. Photo courtesy of UNSW.What interested you about lipids?My five-year doctoral study focused entirely on the enzymes Sterol O-Acyltransferases (SOAT, also known as ACAT, Acyl-CoA Cholesterol Acyltransferases), which catalyze the formation of sterol esters from sterols/cholesterol and fatty acyl CoAs (1). SOATs, integral membrane proteins of the ER, are potential therapeutic targets for heart disease and Alzheimer’s disease. Since then, I have been fascinated by two things related to SOAT: first, what happens upstream of SOAT, i.e., how exogenous cholesterol reaches SOAT/ER; and second, what happens downstream of SOAT, i.e., how its product—cholesterol esters—is stored in cells in the form of lipid droplets (LDs).These are fundamental questions in cell biology. While reading on how cholesterol arrives at the ER for esterification by SOAT/ACAT in the late 1990s, I realized that the trafficking of most lipids was poorly characterized with little molecular insight. Significant progress has been made in the last 20 years, but the lack of tools that track the movement of lipids has hampered our understanding of the selectivity, efficacy, and kinetics of lipid trafficking. Few cell biologists cared about LDs ∼20 years ago, even though LDs are prominent cellular structures in many disease conditions. Each LD comprises a hydrophobic core of storage lipids (triglycerides and sterol esters) wrapped by a monolayer of phospholipids. Largely considered inert lipid granules, LDs originate from the ER and are relatively simple cellular structures as compared with other organelles (see image). Now, we know that LDs are not that simple: their biogenesis is tightly regulated, they actively interact with other organelles, and they regulate many aspects of cellular function as well as disease progression. Astonishingly, we still have little understanding of how LDs originate from the ER. I am very much intrigued by the complexity of these two seemingly simple cellular processes, i.e., lipid trafficking and LD biogenesis.What are some of the scientific questions currently of interest in your laboratory?We are currently focusing on how LDs originate from the ER. The first significant paper from my own laboratory was the discovery of seipin as a key regulator of LD formation (2). Results from many groups have demonstrated that seipin can organize the formation of LDs; however, the exact molecular function of seipin remains mysterious. Our data suggest that seipin may directly impact the level and/or distribution of lipids such as phosphatidic acid near sites of LD biogenesis, and the effect of seipin deficiency on LD formation is secondary to changes in local lipids. We are now working hard to test this hypothesis. Moreover, data from my laboratory and others indicated that nonbilayer lipids may have a greater impact on the biogenesis of LDs than that of other ER-derived structures, such as COPII vesicles. This may result from the monolayer nature of the LD surface. We hope to dissect the dynamic changes of lipids at ER domains where LDs are born. More broadly, the ER is a fascinating organelle to me. The simple division of ER into sheets and tubules does not reflect the dynamic nature of this organelle. Dissecting the composition and organization of lipids and proteins of the ER would help answer key questions relating to LD biogenesis, and it is therefore one of our future directions.Another major focus is to understand how cholesterol and phosphatidylserine are moved between organelles. We have been working on how low-density lipoprotein (LDL)–derived cholesterol (LDL-C) reaches the ER for two decades. The release of LDL-C from lysosomes requires the Niemann Pick C1&2 proteins, whose malfunction causes lysosomal cholesterol accumulation and a lethal genetic disorder affecting young children. The Ara Parseghian Medical Research Foundation has led the way in supporting research into cholesterol trafficking, and I take this opportunity to thank their generous support. Once released from lysosomes, LDL-C is believed to reach the plasma membrane first and then the ER. We identified ORP2 as a possible carrier of LDL-C to the plasma membrane using a PI(4,5)P₂ gradient (3). There must be other carriers and/or pathways because ORP2 deficiency only causes a minor accumulation of cholesterol in lysosomes. Another interesting question is what prevents LDL-C from reaching the ER directly from lysosomes, given the close contact between lysosomes and the ER. We reported that ORP5 may bring LDL-C directly to the ER (4). However, it was later found that ORP5 binds and transfers phosphatidylserine, not cholesterol. Thus, our observed link between ORP5 and cholesterol is through some indirect yet unknown mechanism. We have been perplexed by these observations for many years, but a recent study demonstrated that phosphatidylserine is required for the trafficking of LDL-C, establishing a close link between cholesterol and phosphatidylserine (5). We are now trying to understand how the trafficking and distribution of cholesterol, phosphatidylserine, and PI(4,5)P₂ are interconnected. For a long time, I felt that it was impossible to figure out the molecular details governing the cellular trafficking of lipids due to redundant pathways and a lack of tools to track lipids. Recent progress in this field has given me hope.Lipid droplets in a HeLa cell are shown in red (BODIPY), with their surface in green. DAPI (blue) labels DNA. Image courtesy of Hongyuan Yang.What kind of approach do you bring to your work?Besides honesty and open-mindedness, we emphasize rigor and comprehensiveness. We often make our initial discoveries in cell-based screens. This approach has many advantages, but it also gives rise to artifacts and cell-line specific observations. We aim to complement our initial findings with biochemical and structural analyses in vitro as well as animal studies in vivo. To further establish the reproducibility of our data, I often ask my close friends and collaborators to independently repeat the key findings of a study before submission. It generally takes a long time for us to complete a study, but I believe the effort will pay off in the long run.What did you learn during your training that helped prepare you for being a group leader? What were you unprepared for?During my PhD at Columbia, I was most impressed with the general attitude of my mentors toward research. No matter how much they have achieved, they take every new experiment and every poster presentation seriously.As I did not have postdoctoral training, I was somewhat unprepared at the beginning of my independent career. One difficult challenge was knowing when to finish a paper and project. We often kept working and working. I have now gotten a lot better.You’ve done research on three continents throughout your career. Can you tell us about some of these transitions?During the last year of my doctoral studies at Columbia, I was offered a lecturer position by the Department of Biochemistry at NUS. It was a very hard decision to leave the United States, but I was excited by the prospect of starting my own laboratory at a top institution. Life at NUS was very good overall, despite some struggles. I had to make ∼700 slides for teaching during the first year and my start-up fund was 10,000 Singapore dollars (~6,000 USD). But the graduate students were fully supported by the university, and most of them are hard working and talented. The crucial screen that led to the discovery of seipin as a key regulator of LD formation was performed at NUS (2). I enjoyed my time at NUS, where I was promoted and tenured. However, my family and I could not get used to the heat and humidity. We looked for a place with better climate, and it happened that my current employer, UNSW, had an opening in 2006. Moving continents with two kids was very disruptive, and I had zero publications in 2007. Our work on seipin was delayed and almost got scooped. I was also very worried about funding in Australia since I hardly knew anyone and the funding system. It turned out that the Australian community was very supportive of our research from day one. I have also been very fortunate to receive generous support from the Ara Parseghian Medical Research Foundation, based in the United States, after my move to Sydney.Hongyuan’s “metabolism team” after a basketball game. Photo courtesy of Hongyuan Yang.What has been the biggest accomplishment in your career so far?While I am mostly recognized for discovering seipin’s role in lipid droplet formation, I am prouder of the work we have done on lipid trafficking and the oxysterol binding proteins. We struggled mightily for the first 15 years. At one point in 2015, I seriously considered abandoning this line of research. But we persisted and discovered their roles in regulating plasma membrane PI(4,5)P₂ and cholesterol, as well as in lipid droplet formation (3, 6).What has been the biggest challenge in your career so far?The biggest challenge has to do with the subject of my research topic: the fundamental cell biology of lipids. The sorting, distribution, and storage of cellular lipids are clearly very important topics in biology, but they are sometimes too fundamental to explain to funding agencies and new students. These days, lipid research is not as “sexy” as other topics. But there are so many unanswered questions in lipidology. I strongly believe that lipid research is going to be the next “big thing” as new techniques such as cryoEM now allow us to appreciate lipids and membrane proteins with unprecedented clarity.Who were your key influences early in your career?Besides mentors and teachers at Columbia, I really enjoyed reading and studying the works by Drs. Mike Brown and Joseph Goldstein, Ta-Yuan Chang, and Scott Emr. While they were not my teachers, their work inspired and impacted many young scientists, including me.What is the best advice you have been given?I have been given many pieces of great advice during my career. The best one in my view is “Less is more.” I was once told, “You would be better off with a lab of six than twelve.” Initially, I did not get it because I thought that a bigger group would allow me to explore more directions and be more productive. The reality is that, as a little-known junior researcher, few experienced people would join my laboratory. Funding is also a major limiting factor. Supervising a large number of students is fulfilling, but it also takes away some of my own time to think critically about the projects. I have largely kept my group under six, and this allows me to better supervise and guide the trainees. People say, “Once your team has more than 15 members, you become a manager instead of a scientist.” My own experience corroborates that statement because I struggled quite a bit when my group reached 12 at one point.What hobbies do you have?I am heavily into sports, especially basketball and tennis. I follow the NBA closely, and Jeremy Lin is my hero. I still play basketball at least twice a week. I am the captain of a basketball team comprised of scientists working on metabolism (see image). We play real, refereed basketball games against local teams during conferences. As I am getting older, I have also picked up tennis. I watch coaching videos on YouTube but still need a lot of work on my forehand. Through sports, I learned teamwork and the spirit of fighting to the last second. If I were not a scientist, I would probably run a sports-related business.What has been your biggest accomplishment outside of the laboratory?I got married and had children relatively early. Both of my kids are now in college and they appear to be decent human beings. I have been extremely lucky because my wife did most of the heavy lifting in looking after the kids. It was still a struggle for me to balance work and parental duties during the early days of my independent career. I am very proud and happy with where we are as a family right now.Any tips for a successful research career?Everyone is unique. Knowing your strengths and especially your weaknesses can be crucial to your success. My undergraduate training was in medicine and health management, and my PhD work focused on genetics and cell biology, so my understanding of physical chemistry is rather inadequate. I am also very bad at developing new methods. To alleviate these deficiencies, I constantly monitor new methods in my field and I purposefully look for collaborators with strong chemistry backgrounds. I have benefited immensely from such efforts.     

Claude Bernard Distinguished Lecture. Becoming a truly helpful teacher: considerably more challenging, and potentially more fun, than merely doing business as usual

Few medical faculty members are adequately prepared for their instructional responsibilities. Our educational traditions were established before we had research-based understandings of the teaching-learning process and before brain research began informing our understandings of how humans achieve lasting learning. Yet, there are several advantages you may have. If your expertise is at one of the frontiers of human biology, your teaching can be inherently fascinating to aspiring health professionals. If your work has implications for human health, you have another potential basis for engaging future clinicians. And, thanks to Claude Bernard's influence, you likely are "process oriented," a necessary mindset for being an effective teacher. There are also challenges you may face. Your medical students will mostly become clinicians. Unless you can help them see connections between your offerings and their future work, you may not capture and sustain their interest. To be effective, teachers, like clinicians, need to be interactive, make on-the-spot decisions, and be "emotional literate." If you aren't comfortable with these demands, you may have work to do toward becoming a truly helpful teacher. Program changes may be needed. Might your program need to change 1) from being adversarial and controlling to being supportive and trust based or 2) from mainly dispensing information to mainly asking and inviting questions? In conclusion, making changes toward becoming a truly helpful teacher can bring benefits to your students while increasing your sense of satisfaction and fulfillment as a teacher. If you choose to change, be gentle with yourself, as you should be when expecting your students to make important changes.