The economic approach to ‘theory of mind’

Theory of mind (ToM) is a great evolutionary achievement. It is a special intelligence that can assess not only one''s own desires and beliefs, but also those of others. Whether it is uniquely human or not is controversial, but it is clear that humans are, at least, significantly better at ToM than any other animal. Economists and game theorists have developed sophisticated and powerful models of ToM and we provide a detailed summary of this here. This economic ToM entails a hierarchy of beliefs. I know my preferences, and I have beliefs (a probabilistic distribution) about your preferences, beliefs about your beliefs about my preferences, and so on. We then contrast this economic ToM with the theoretical approaches of neuroscience and with empirical data in general. Although this economic view provides a benchmark and makes useful suggestions about empirical tendencies, it does not always generate a close fit with the data. This provides an opportunity for a synergistic interdisciplinary production of a falsifiable theory of bounded rationality. In particular, a ToM that is founded on evolutionary biology might well be sufficiently structured to have predictive power, while remaining quite general. We sketch two papers that represent preliminary steps in this direction.     

Objectivity and Illusion in Evolutionary Ethics: Comments on Waller

In this paper I argue that any adequate evolutionary ethical theory needs to account for moral belief as well as for dispositions to behave altruistically. It also needs to be clear whether it is offering us an account of the motivating reasons behind human behaviour or whether it is giving justifying reasons for a particular set of behaviours or, if both, to distinguish them clearly. I also argue that, unless there are some objective moral truths, the evolutionary ethicist cannot offer justifying reasons for a set of behaviours. I use these points to refute Waller's claims that the illusion of objectivity plays a dispensable role in Ruse's theory, that my critique of Ruse's Darwinian metaethics is built on a false dilemma, that there is nothing to be distressed about if morality is not objective, and that ethical beliefs are subject to a kind of causal explanation that undermines their objectivity in a way that scientific beliefs are not.     

Units and passages: A view for evolutionary biology and ecology

Many authors, including paleobiologists, cladists and so on, adopt a nested hierarchical viewpoint to examine the relationships among different levels of biological organization. Furthermore, species are often considered to be unique entities in functioning evolutionary processes and one of the individuals forming a nested hierarchy.I have attempted to show that such a hierarchical view is inadequate in evolutionary biology. We should define units depending on what we are trying to explain. Units that play an important role in evolution and ecology do not necessarily form a nested hierarchy. Also the relationships among genealogies at different levels are not simply nested. I have attempted to distinguish the different characteristics of passages when they are used for different purposes of explanation. In my analysis, species and monophyletic taxa cannot be uniquely defined as single units that function in ecological and evolutionary processes.The view discussed in this paper may provide a more general basis for testing competing theories in evolution, and provide new insights for future empirical studies.     

After 2 years of a pandemic,students are struggling to find strong reference letters

Writing and receiving reference letters in the time of COVID. Subject Categories: Careers

“People influence people. Nothing influences people more than a recommendation from a trusted friend. A trusted referral influences people more than the best broadcast message.” —Mark Zuckerberg.

I regularly teach undergraduate courses in genetics and genomics. Sure enough, at the end of each semester, after the final marks have been submitted, my inbox is bombarded with reference letter requests. “Dear Dr. Smith, I was a student in your Advanced Genetics course this past term and would be forever grateful if you would write me a reference for medical school…” I understand how hard it can be to find references, but I have a general rule that I will only write letters of support for individuals that I have interacted with face‐to‐face on at least a few occasions. This could include, for example, research volunteers in my laboratory, honors thesis students that I have supervised, and students who have gone out of their way to attend office hours and/or been regularly engaged in class discussions. I am selective about who I will write references for, not because I am unkind or lazy, but because I know from experience that a strong letter should include concrete examples of my professional interactions with the individual and should speak to their character and their academic abilities. In today''s highly competitive educational system, a letter that merely states that a student did well on the midterm and final exams will not suffice to get into medical or graduate school.However, over the past 2 years many, if not most, students have been attending university remotely with little opportunity to foster meaningful relationships with their instructors, peers, and mentors, especially for those in programs with large enrollments. Indeed, during the peak of Covid‐19, I stopped taking on undergraduate volunteers and greatly reduced the number of honors students in my laboratory. Similarly, my undergraduate lectures have been predominantly delivered online via Zoom, meaning I did not see or speak with most of the students in my courses. It did not help that nearly all of them kept their cameras and microphones turned off and rarely attended online office hours. Consequently, students are desperately struggling to identify individuals who can write them strong letters of reference. In fact, this past spring, I have had more requests for reference letters than ever before, and the same is true for many of my colleagues. Some of the emails I have received have been heartfelt and underscore how taxing the pandemic has been on young adults. With permission, I have included an excerpt from a message I received in early May:Hi Dr. Smith. You may not remember me, but I was in Genome Evolution this year. I enjoyed the class despite being absent for most of your live Zoom lectures because of the poor internet connection where I live. Believe it or not, my mark from your course was the highest of all my classes this term! Last summer, I moved back home to rural Northern Ontario to be closer to my family. My mom is a frontline worker and so I''ve been helping care for my elderly grandmother who has dementia as well as working part‐time as a tutor at the local high school to help pay tuition. All of this means that I''ve not paid as much attention to my studies as I should have. I''m hoping to go to graduate school this coming fall, but I have yet to find a professor who will write a reference for me. Would you please, please consider writing me a letter?I am sympathetic to the challenges students faced and continue to face during Covid‐19 and, therefore, I have gone out of my way to provide as many as I can with letters of support. But, it is no easy feat writing a good reference for someone you only know via an empty Zoom box and a few online assignments. My strategy has been to focus on their scholarly achievements in my courses, providing clear, tangible examples from examinations and essays, and to highlight the notable aspects of their CVs. I also make a point to stress how hard online learning can be for students (and instructors), reiterating some of the themes touched upon above. This may sound unethical to some readers but, in certain circumstances, I have allowed students to draft their own reference letters, which I can then vet, edit, and rewrite as I see fit.But it is not just undergraduates. After months and months of lockdowns and social distancing, many graduate students, postdocs, and professors are also struggling to find suitable references. In April, I submitted my application for promotion to Full Professor, which included the names of 20 potential reviewers. Normally, I would have selected at least some of these names from individuals I met at recent conferences and invited to university seminars, except I have not been to a conference in over 30 months. Moreover, all my recent invited talks have been on Zoom and did not include any one‐on‐one meetings with faculty or students. Thus, I had to include the names of scientists that I met over 3 years ago, hoping that my research made a lasting impression on them. I have heard similar anecdotes from many of my peers both at home and at other universities. Given all of this, I would encourage academics to be more forthcoming than they may have traditionally been when students or colleagues approach them for letters of support. Moreover, I think we could all be a little more forgiving and understanding when assessing our students and peers, be it for admissions into graduate school, promotion, or grant evaluations.Although it seems like life on university campuses is returning to a certain degree of normality, many scholars are still learning and working remotely, and who knows what the future may hold with regard to lockdowns. With this uncertainty, we need to do all we can to engage with and have constructive and enduring relationships with our university communities. For undergraduate and graduate students, this could mean regularly attending online office hours, even if it is only to introduce yourself, as well as actively participating in class discussions, whether they are in‐person, over Zoom, or on digital message boards. Also, do not disregard the potential and possibilities of remote volunteer research positions, especially those related to bioinformatics. Nearly, every laboratory in my department has some aspect of their research that can be carried out from a laptop computer with an Internet connection. Although not necessarily as enticing as working at the bench or in the field, computer‐based projects can be rewarding and an excellent path to a reference letter.If you are actively soliciting references, try and make it as easy as possible on your potential letter writers. Clearly and succinctly outline why you want this person to be a reference, what the letter writing/application process entails, and the deadline. Think months ahead, giving your references ample time to complete the letter, and do not be shy about sending gentle reminders. It is great to attach a CV, but also briefly highlight your most significant achievements in bullet points in your email (e.g., Dean''s Honours List 2021–22). This will save time for your references as they will not have to sift through many pages of a CV. No matter the eventual result of the application or award, be sure to follow up with your letter writers. There is nothing worse than spending time crafting a quality support letter and never learning the ultimate outcome of that effort. And, do not be embarrassed if you are unsuccessful and need to reach out again for another round of references—as Winston Churchill said, “Success is stumbling from failure to failure with no loss of enthusiasm.”     

Can biology make ethics objective?

A familiar position regarding the evolution of ethics is that biology can explain the origin of morals but that in doing so it removes the possibility of their having objective justification. This position is set fourth in detail in the writings of Michael Ruse (1986, 1987, 1989, 1990a, 1990b) but it is also taken by many others, notably, Jeffrie Murphy (1982), Andrew Oldenquist (1990), and Allan Gibbard (1990), I argue the contrary view that biology provides a justification of the existence of morals which is objective in the sense of being independent of people's moral views and their particular desires and preferences. Ironically, my argument builds on the very premises which are supposed to undermine the objectivity of morals. But my argument stops short of claiming that biology can give us a basis for justifying some particular system of morals. Drawing on an analogy with social contract theory, I offer a general reason why this more ambitious project cannot be expected to succeed if the argument is pursued along the same lines. Finally, I give reasons why the possibility of objective justification for a particular morality cannot be ruled out in general on evolutionary grounds.     

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.     

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.     

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.     

Dr. Manners

Good manners make a difference—in science and elsewhere. This includes our social media etiquette as researchers. Subject Categories: S&S: History & Philosophy of Science, Methods & Resources, S&S: Ethics

Elbows off the table, please. Don’t chew with your mouth open. Don’t blow your nose at the table. Don’t put your feet up on the chair or table. And please, do not yuck my yum. These are basic table manners that have come up at some of our lab meals, and I have often wondered if it was my job to teach my trainees social graces. A good fellow scientist and friend of mine once told me it was absolutely our place as mentors to teach our trainees not only how to do science well, but also how to be well‐mannered humans. While these Emily Post‐approved table manners might seem old‐fashioned (I’m guessing some readers will have to look up Emily Post), I strongly believe they still hold a place in modern society; being in good company never goes out of style.Speaking of modern society: upon encouragement by several of my scientist friends, I joined Twitter in 2016. My motivation was mainly to hear about pre‐prints and publications, conference announcements and relevant news, science or otherwise. I also follow people who just make me laugh (I highly recommend @ConanOBrien or @dog_rates). I (re)tweet job openings, conference announcements, and interesting new data. Occasionally, I post photos from conferences, or random science‐related art. I also appreciate the sense of community that social media brings to the table. However, social media is a venue where I have also seen manners go to die. Rapidly.It is really shocking to read what some people feel perfectly comfortable tweeting. While most of us can agree that foul language and highly offensive opinions are generally considered distasteful, there are other, subtler but nonetheless equally—if not more—cringe‐worthy offenses online when I am fairly certain these people would never utter such words in real life. In the era of pandemic, the existence of people tweeting about not being able to eat at their favorite restaurant or travel to some destination holiday because of lockdown shows an egregious lack of self‐awareness. Sure it sucks to cancel a wedding due to COVID‐19, but do you need to moan to your followers—most of whom are likely total strangers—about it while other people have lost their jobs? If I had a nickel for every first‐world complaint I have seen on Twitter, I’d have retired a long time ago; although to be honest, I would do science for free. However, these examples pale in comparison with another type of tweeter: Reader, I submit to you, “the Humblebragger.”From the MacMillan Buzzword dictionary (via Google): a humblebrag is “a statement in which you pretend to be modest but which you are really using as a way of telling people about your success or achievements.” I would further translate this definition to indicate that humblebraggers are starved for attention. After joining Twitter, I quickly found many people using social media to announce how “humble and honored” they are for receiving grant or prize X, Y, or Z. In general, these are junior faculty who have perhaps not acquired the self‐awareness more senior scientists have. Perhaps the most off‐putting posts I have seen are from people who post photos of their NIH application priority scores right after study section, or their Notice of Awards (NOA). When did we ever, before social media, send little notes to each other—let alone to complete strangers—announcing our priority scores or NOAs? (Spoiler: NEVER)Some of you reading this opinion piece might have humblebragged at one or time or another, and might not understand why it is distasteful. Please let me explain. For every person who gets a fundable score, there are dozens more people who do not, and they are sad (I speak from many years of experience). While said fundable‐score person might be by someone we like—and I absolutely, positively wish them well—there are many more people who will feel lousy because they did not get funding from the same review round. When has anyone ever felt good about other people getting something that they, too, desire? I think as children, none of us liked the kid on the playground who ran around with the best new Toy of the Season. As adults, do we feel differently? Along these lines, I have never been a fan of “best poster/talk/abstract” prizes. Trainees should not be striving for these fleeting recognitions and should focus on doing the best science for Science’s sake; I really believe this competition process sets people up for life in a negative way—there, I’ve said it.Can your friends and colleagues tweet about your honors? Sure, why not, and by all means please let your well‐wishers honor you, and do thank them and graciously congratulate your trainees or colleagues for helping you to get there. But to post things yourself? Please. Don’t be surprised if you have been muted by many of your followers.It is notable that many of our most decorated scientists are not on Twitter, or at least never tweet about their accomplishments. I do not recall ever seeing a single Nobel laureate announce how humbled and honored they are about their prize. Of course, I might be wrong, but I am willing to bet the numbers are much lower than what I have observed for junior faculty. True humility will never be demonstrated by announcing your achievements to your social media followers, and I believe humblebragging reveals insecurity more than anything. I hope that many more of us can follow the lead of our top scientists both in creativity, rigor, and social media politeness.     

Exploring the Relationships among Epistemological Beliefs, Nature of Science, and Conceptual Change in the Learning of Evolutionary Theory

We explored the relationship between epistemological beliefs and nature of science in a college biology course. One hundred thirty-three college students participated in the research. Exploratory factor analysis with 29 Nature of Science (NOS) items yielded three aspects of NOS: empirical, tentative, and sociocultural nature of scientific knowledge. Pearson r correlations suggested that students who have immature epistemological beliefs are more likely to also have immature beliefs of nature of science. In addition, students’ epistemological beliefs significantly correlate with their conceptual change but their beliefs about nature of science did not. The research is significant in that it provides empirical evidence explaining the relationship between students’ epistemological beliefs and nature of science as well as the relationships between epistemological beliefs and conceptual change in evolution theory.     

Work life balance?

There is no perfect recipe to balance work and life in academic research. Everyone has to find their own optimal balance to derive fulfilment from life and work. Subject Categories: S&S: Careers & Training

A few years ago, a colleague came into my office, looking a little irate, and said, “I just interviewed a prospective student, and the first question was, ‘how is work‐life balance here?’”. Said colleague then explained how this question was one of his triggers. Actually, this sentiment isn''t unusual among many PIs. And, yet, asking about one''s expected workload is a fair question. While some applicants are actually coached to ask it at interviews, I think that many younger scientists have genuine concerns about whether or not they will have enough time away from the bench in order to have a life outside of work.In a nutshell, I believe there is no one‐size‐fits‐all definition of work–life balance (WLB). I also think WLB takes different forms depending on one''s career stage. As a new graduate student, I didn''t exactly burn the midnight oil; it took me a couple of years to get my bench groove on, but once I did, I worked a lot and hard. I also worked on weekends and holidays, because I wanted answers to the questions I had, whether it was the outcome of a bacterial transformation or the result from a big animal experiment. As a post‐doc, I worked similarly hard although I may have actually spent fewer hours at the bench because I just got more efficient and because I read a lot at home and on the six train. But I also knew that I had to do as much as I could to get a job in NYC where my husband was already a faculty member. The pressure was high, and the stress was intense. If you ask people who knew me at the time, they can confirm I was also about 30 pounds lighter than I am now (for what it''s worth, I was far from emaciated!).As an assistant professor, I still worked a lot at the bench in addition to training students and writing grant applications (it took me three‐plus years and many tears to get my first grant). As science started to progress, work got even busier, but in a good way. By no means did I necessarily work harder than those around me—in fact, I know I could have worked even more. And I’m not going to lie, there can be a lot of guilt associated with not working as much as your neighbor.My example is only one of millions, and there is no general manual on how to handle WLB. Everyone has their own optimal balance they have to figure out. People with children or other dependents are particularly challenged; as someone without kids, I cannot even fathom how tough it must be. Even with some institutions providing child care or for those lucky enough to have family take care of children, juggling home life with “lab life” can create exceptional levels of stress. What I have observed over the years is that trainees and colleagues with children become ridiculously efficient; they are truly remarkable. One of my most accomplished trainees had two children, while she was a post‐doc and she is a force to be reckoned with—although no longer in my laboratory, she still is a tour de force at work, no less with child number three just delivered! I think recruiters should view candidates with families as well—if not better—equipped to multi‐task and get the job done.There are so many paths one can take in life, and there is no single, “correct” choice. If I had to define WLB, I would say it is whatever one needs to do in order to get the work done to one''s satisfaction. For some people, putting in long days and nights might be what is needed. Does someone who puts in more hours necessarily do better than one who doesn''t, or does a childless scientist produce more results than one with kids? Absolutely not. People also have different goals in life: Some are literally “wedded” to their work, while others put much more emphasis on spending time with their families and see their children grow up. Importantly, these goals are not set in stone and can fluctuate throughout one''s life. Someone recently said to me that there can be periods of intense vertical growth where “balance” is not called for, and other times in life where it is important and needed. I believe this sentiment eloquently sums up most of our lives.Now that I''m a graying, privileged professor, I have started to prioritize other areas of life, in particular, my health. I go running regularly (well, maybe jog very slowly), which takes a lot of time but it is important for me to stay healthy. Pre‐pandemic, I made plans to visit more people in person as life is too short not to see family and friends. In many ways, having acquired the skills to work more efficiently after many years in the laboratory and office, along with giving myself more time for my health, has freed up my mind to think of science differently, perhaps more creatively. It seems no matter how much I think I’m tipping the balance toward life, work still creeps in, and that’s perfectly OK. At the end of the day, my work is my life, gladly, so I no longer worry about how much I work, nor do I worry about how much time I spend away from it. If you, too, accomplish your goals and derive fulfillment from your work and your life, neither should you.     

Neural systems involved in "theory of mind"

What is the nature of our ability to understand and reason about the beliefs of others--the possession of a "theory of mind", or ToM? Here, we review findings from imaging and lesion studies indicating that ToM reasoning is supported by a widely distributed neural system. Some functional components of this system, such as language-related regions of the left hemisphere, the frontal lobes and the right temporal parietal cortex, are not solely dedicated to the computation of mental states. However, the system also includes a core, domain-specific component that is centred on the amygdala circuitry. We provide a framework in which impairments of ToM can be viewed in terms of abnormalities of the core system, the failure of a co-opted system that is necessary for performance on a particular set of tasks, or the absence of an experiential trigger for the emergence of ToM.     

Evolutionary arguments against moral realism: Why the empirical details matter (and which ones do)

The aim of this article is to identify the strongest evolutionary debunking argument (EDA) against moral realism and to assess on which empirical assumptions it relies. In the recent metaethical literature, several authors have de-emphasized the evolutionary component of EDAs against moral realism: presumably, the success or failure of these arguments is largely orthogonal to empirical issues. I argue that this claim is mistaken. First, I point out that Sharon Street’s and Michael Ruse’s EDAs both involve substantive claims about the evolution of our moral judgments. Next, I argue that combining their respective evolutionary claims can help debunkers to make the best empirical case against moral realism. Some realists have argued that the very attempt to explain the contents of our endorsed moral judgments in evolutionary terms is misguided, and have sought to escape EDAs by denying their evolutionary premise. But realists who pursue this reply can still be challenged on empirical grounds: debunkers may argue that the best, scientifically informed historical explanations of our moral endorsements do not involve an appeal to mind-independent truths. I conclude, therefore, that the empirical considerations relevant for the strongest empirically driven argument against moral realism go beyond the strictly evolutionary realm; debunkers are best advised to draw upon other sources of genealogical knowledge as well.     

The sociobiology of ethnocentrism in an Indian City

In this article, I examine whether inter- and/or intraunit variation in ethnocentrism— a trait not automatically connected with mortality/natality rates—can be correlated with differential reproductive success. As a preliminary test of general theoretical models in the literature regarding the sociobiology of ethnocentrism, it was postulated that the more ethnocentric an ethnic unit is, the more important ethnocentrism is for the members of that unit. With the use of this postulate, hypotheses were generated and tested with empirical data obtained through field research among two ethnic units—Tamils and Gujaratis—in the city of Pune, India. It was concluded that: 1) if interunit aggression and kin selection were predominant characteristics of the early hominid environments of evolutionary adaptation, then from a sociobiological perspective, ethnocentrism can be explained as an evolved human trait, intimately linked to kin selection and interunit warfare; and, 2) under what I assumed to be novel environmental conditions ethnocentrism and reproductive success appear to be uncorrelated; and, 3) because the possibility exists that novel environmental contengencies were acting to level off reproductive variance upon which natural selection could have operated in my sample, only future research in a society similar in structure to those we tend to identify with early hominid environments of evolutionary adaptation will allow researchers to rule out the possibility that ethnocentrism is an evolved human “biocultural” trait.     

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     

Evolutionary ethics from Darwin to Moore

Evolutionary ethics has a long history, dating all the way back to Charles Darwin. Almost immediately after the publication of the Origin, an immense interest arose in the moral implications of Darwinism and whether the truth of Darwinism would undermine traditional ethics. Though the biological thesis was certainly exciting, nobody suspected that the impact of the Origin would be confined to the scientific arena. As one historian wrote, 'whether or not ancient populations of armadillos were transformed into the species that currently inhabit the new world was certainly a topic about which zoologists could disagree. But it was in discussing the broader implications of the theory...that tempers flared and statements were made which could transform what otherwise would have been a quiet scholarly meeting into a social scandal' (Farber 1994, 22). Some resistance to the biological thesis of Darwinism sprung from the thought that it was incompatible with traditional morality and, since one of them had to go, many thought that Darwinism should be rejected. However, some people did realize that a secular ethics was possible so, even if Darwinism did undermine traditional religious beliefs, it need not have any effects on moral thought. Before I begin my discussion of evolutionary ethics from Darwin to Moore, I would like to make some more general remarks about its development. There are three key events during this history of evolutionary ethics. First, Charles Darwin published On the Origin of the Species (Darwin 1859). Since one did not have a fully developed theory of evolution until 1859, there exists little work on evolutionary ethics until then. Shortly thereafter, Herbert Spencer (1898) penned the first systematic theory of evolutionary ethics, which was promptly attacked by T.H. Huxley (Huxley 1894). Second, at about the turn of the century, moral philosophers entered the fray and attempted to demonstrate logical errors in Spencer's work; such errors were alluded to but never fully brought to the fore by Huxley. These philosophers were the well known moralists from Cambridge: Henry Sidgwick (Sidgwick 1902, 1907) and G.E. Moore (Moore 1903), though their ideas hearkened back to David Hume (Hume 1960). These criticisms were so strong that the industry of evolutionary ethics was largely abandoned (though with some exceptions) for many years. Third, E.O. Wilson, a Harvard entomologist, published Sociobiology: The New Synthesis in 1975 (Wilson E.O. 1975), which sparked renewed interest in evolutionary ethics and offered new directions of investigation. These events suggest the following stages for the history of evolutionary ethics: development, criticism and abandonment, revival. In this paper, I shall focus on the first two stages, since those are the ones on which the philosophical merits have already been largely decided. The revival stage is still in progress and we shall eventually find out whether it was a success.     

A new bayesian method for fitting evolutionary models to comparative data with intraspecific variation

Phylogenetic comparative methods that incorporate intraspecific variability are relatively new and, so far, not especially widely used in empirical studies. In the present short article we will describe a new Bayesian method for fitting evolutionary models to comparative data that incorporates intraspecific variability. This method differs from an existing likelihood-based approach in that it requires no a priori inference about species means and variances; rather it takes phenotypic values from individuals and a phylogenetic tree as input, and then samples species means and variances, along with the parameters of the evolutionary model, from their joint posterior probability distribution. One of the most novel and intriguing attributes of this approach is that jointly sampling the species means with the evolutionary model parameters means that the model and tree can influence our estimates of species mean trait values, not just the reverse. In the present implementation, we first apply this method to the most widely used evolutionary model for continuously valued phenotypic trait data (Brownian motion). However, the general approach has broad applicability, which we illustrate by also fitting the λ model, another simple model for quantitative trait evolution on a phylogeny. We test our approach via simulation and by analyzing two empirical datasets obtained from the literature. Finally, we have implemented the methods described herein in a new function for the R statistical computing environment, and this function will be distributed as part of the 'phytools' R library.     

Evolutionary convergences and parallelisms: &;their theoretical differences and the difficulty &;of discriminating them in a practical &;phylogenetic context

The importance of evolutionary parallelisms and their differences from evolutionary convergences have been historically underappreciated, as recently noticed in Gould's last book `The structure of evolutionary history'. In that book, Gould make an effort to distinguish and to reinterpret these concepts in the light of the new discoveries of the last decades on developmental biology and genetics, presenting the elegant metaphor of `Pharaonic bricks versus Corinthian columns'. In this paper I will briefly discuss these concepts, and will argue that, despite the advances that have been made to define them in theory, it is rather hard to differentiate them in a practical phylogenetic context. In order to do so, I will provide some few examples from my own empirical studies on the last years of one of the most morphologically and taxonomically diverse groups of Vertebrates, the catfishes.