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     

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!     

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.     

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.     

Interpretation of diagnostic data: 4. How to do it with a more complex table.

A more complex table is especially useful when a diagnostic test produces a wide range of results and your patient''s levels are near one of the extremes. The following guidelines will be useful: Identify the several cut-off points that could be used. Fill in a complex table along the lines of Table I, showing the numbers of patients at each level who have and do not have the target disorder. Generate a simple table for each cut-off point, as in Table II, and determine the sensitivity (TP rate) and specificity (TN rate) at each of them. Select the cut-off point that makes the most sense for your patient''s test result and proceed as in parts 2 and 3 of our series. Alternatively, construct an ROC curve by plotting the TP and FP rates that attend each cut-off point. If you keep your tables and ROC curves close at hand, you will gradually accumulate a set of very useful guides. However, if you looked very hard at what was happening, you will probably have noticed that they are not very useful for patients whose test results fall in the middle zones, or for those with just one positive result of two tests; the post-test likelihood of disease in these patients lurches back and forth past 50%, depending on where the cut-off point is. We will show you how to tackle this problem in part 5 of our series. It involves some maths, but you will find that its very powerful clinical application can be achieved with a simple nomogram or with some simple calculations.     

Bioinformatics meets user-centred design: a perspective

Designers have a saying that "the joy of an early release lasts but a short time. The bitterness of an unusable system lasts for years." It is indeed disappointing to discover that your data resources are not being used to their full potential. Not only have you invested your time, effort, and research grant on the project, but you may face costly redesigns if you want to improve the system later. This scenario would be less likely if the product was designed to provide users with exactly what they need, so that it is fit for purpose before its launch. We work at EMBL-European Bioinformatics Institute (EMBL-EBI), and we consult extensively with life science researchers to find out what they need from biological data resources. We have found that although users believe that the bioinformatics community is providing accurate and valuable data, they often find the interfaces to these resources tricky to use and navigate. We believe that if you can find out what your users want even before you create the first mock-up of a system, the final product will provide a better user experience. This would encourage more people to use the resource and they would have greater access to the data, which could ultimately lead to more scientific discoveries. In this paper, we explore the need for a user-centred design (UCD) strategy when designing bioinformatics resources and illustrate this with examples from our work at EMBL-EBI. Our aim is to introduce the reader to how selected UCD techniques may be successfully applied to software design for bioinformatics.     

Interpretation of diagnostic data: 3. How to do it with a simple table (part B).

The following guidelines are useful if you want to "do it with a simple table" (Table IV): First, identify the sensitivity and specificity of the sign, symptom or diagnostic test you plan to use. Many are already in the literature, and subspecialists should either know them for their field or be able to track them down for you. Depending on whether you are considering a sign, a symptom or a diagnostic laboratory test, you will want to track down a clinical subspecialist, a radiologist, a pathologist and so on. Start your table with a total of 1000 patients, as shown in location (a + b + c + d) of panel A. Using the information you have about the patient before you apply the diagnostic test, estimate the patient''s pretest likelihood (prevalence or prior probability) of the target disorder -- let''s say 10%. Take this proportion of the total (100) and place it in location (a + c); the remaining 900 patients go in location (b + d) (panel B). Multiply (a + c) (100) by the sensitivity of the diagnostic test (let''s say 83%) and place the result (83) in cell a and the difference (17) in cell c; similarly, multiply (b + d) (900) by the specificity of the diagnostic test (let''s say 91%) and place the result (819) in cell d and the difference (81) in cell b (panel C). If (a + b) and (c + d) do not add up to 1000, you will know you have made a mistake. You can now calculate the positive predictive value, a/(a + b), and the negative predictive value, d/(c + d), as shown in panel D. You have now reached a level of understanding a fair bit beyond the rule-in/rule-out strategy discussed in part 1 of our series. Furthermore, you can already do more than most clinicians, so you may want to stop here, at least for a while. On the other hand, you may want to go further and learn how to handle slightly more complex tables with multiple cut-off points. In the next article you will find more powerful ways to take advantage of the degree of positivity and negativity of diagnostic test results.     

Advance directives, autonomy and unintended death

This Paper argues that Living wills are typically nebulous and confused documents that do not effectively enable you to determine your future treatment. Worse, signing a living will can end your life in ways you never intended, long before you are either incompetent or terminally ill. This danger is compounded by the fact that those who implement living wills are often themselves dangerously confused, so that, for example, they cannot be relied upon to distinguish living wills from DNR orders. In addition, the Paper argues that advance directives concerning resuscitation are often so confused that they end the lives of healthy, alert people who have not suffered cardiac or pulmonary arrest. Finally, the paper argues that advance directives establishing durable power of attorney for health care often preserve the chief dangers of living wills. Suggestions are offered as to how you can most effectively direct your future treatment without endangering your life.     

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?     

How to succeed in science

Adherence to these principles will not guarantee success, but the testimony of many famous scientists supports the hypothesis that these guidelines can significantly (p less than .05, Wilcoxon unpaired X-test run at pH 5.6) increase your chances of achieving recognition, acquiring wealth, and ultimately being known as a successful scientist. At the very least, they should prevent you from falling too far outside the boundaries of "normal" science where you could easily be branded for life as a troublemaker or heretic.     

Interpretation of diagnostic data: 6. How to do it with more complex maths.

We have now shown you how to use decision analysis in making those rare, tough diagnostic decisions that are not soluble through other, easier routes. In summary, to "use more complex maths" the following steps will be useful: Create a decision tree or map of all the pertinent courses of action and their consequences. Assign probabilities to the branches of each chance node. Assign utilities to each of the potential outcomes shown on the decision tree. Combine the probabilities and utilities for each node on the decision tree. Pick the decision that leads to the highest expected utility. Test your decision for its sensitivity to clinically sensible changes in probabilities and utilities. That concludes this series of clinical epidemiology rounds. You''ve come a long way from "doing it with pictures" and are now able to extract most of the diagnostic information that can be provided from signs, symptoms and laboratory investigations. We would appreciate learning whether you have found this series useful and how we can do a better job of presenting these and other elements of "the science of the art of medicine".     

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.     

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.     

The most unkindest cut

When universities need to make staffing cuts to balance the books, do they always do so in the fairest and most rational manner?

Universities, like most other large organizations, undergo periodic restructuring, expansions and contractions, driven largely by changes in their balance sheet. The contractions are often abrupt and painful. Typically, this outcome is preceded by a period when the top management already perceived a growing problem but postponed action because of its debilitating effects on morale and on the organization’s core functions, in the hope that “something might turn up” that would obviate the need for drastic cuts. Most often, something does not turn up, and the cuts end up being even more severe.The first sign of trouble is usually a “message to all staff” that seems to come out of the blue, couched in the most anodyne of terms, or even trying to put a positive spin on what is a fundamentally destructive process. But staff about to be made redundant do not appreciate being referred to as “person‐years”. It also seems completely pointless to dress up more or less arbitrary decisions on whom to terminate as “negotiations”, thus apportioning a share of blame to the union representatives who have not much say in these “negotiations” anyway. Although the cuts typically affect non‐academic staff, such as lab technicians, IT and audiovisual support, financial administrators, providers of student welfare services or travel and hospitality arrangers, academic staff at all levels are sometimes affected as well.Most of us can read between the lines and find disingenuous statements of this type insulting rather than reassuring. Let me translate this for you into plain English:“Due to the fact that our senior management has totally screwed up the university’s finances, we need to decrease our staff costs by 20%. Since most staff would not accept to do the same work for 20% less pay, we will instead just fire 20% of the staff. If you are one of the 20% who are able to do your job and have been properly trained, we strongly advise you to immediately seek employment elsewhere. After all, you might find yourselves fired in the next round of cuts, if these ones don’t prove sufficient”.The duties of the 20% who leave will be transferred to the 80% who remain. Since they will be required to carry out additional tasks beyond those that they currently undertake but were never trained to perform in the first place, it is natural that many of them will go on permanent sick leave or retire early, thus reducing our staff costs further and avoiding undue stress on persons we have failed to train properly.As a result, academic staff currently engaged on less quantifiable activities such as research and teaching must shoulder some of the burden. We hope to avoid firing academic staff but be aware that you may also be terminated if performance targets are missed, especially if you are unable to undertake simple obligations to help the university to function properly instead of wasting all your energy on research and teaching.The next phase of this process will be the outsourcing of many of the duties that the poorly trained 80% of staff and academics cannot do or are unwilling to do. We will invite tenders from different companies and always pick the lowest bidder, regardless of the quality of the services they are able to perform. However, be aware that academic staff who make use of these services must employ the companies contracted by the university and no others. You will also have to pay for these services from research grants or other income.Spin‐off companies that you have created could also bid for some of these services, which might enable you to cover the costs during the 2–3 years before your fledgling company goes bankrupt.Please also consider if and how you can outsource your own research and teaching, which would enable us to fire academic staff as well, in any future cost‐cutting exercise.If this process is successful, the university hopes to recycle any excess savings into a new round of Strategic Interconvertibility and Sustainable Innovation (SISI) grants.And above all, please do remember and implement our university’s new slogan “The only useful research is market research”. Kit from HR, aka Howy Jacobs     

Learn from the Best

What is more inspiring than a discussion with the leading scientists in your field? As a student or a young researcher, you have likely been influenced by mentors guiding you in your career and leading you to your current position. Any discussion with or advice from an expert is certainly very helpful for young people. But how often do we have the opportunity to meet experts? Do we make the most out of these situations? Meetings organized for young scientists are a great opportunity not only for the attendees: they are an opportunity for experts to meet bright students and learn from them in return. In this article, we introduce several successful events organized by Regional Student Groups all around the world, bridging the gap between experts and young scientists. We highlight how rewarding it is for all participants: young researchers, experts, and organizers. We then discuss the various benefits and emphasize the importance of organizing and attending such meetings. As a young researcher, seeking mentorship and additional skills training is a crucial step in career development. Keep in mind that one day, you may be an inspiring mentor, too.     

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.     

A patient's guide to choosing unconventional therapies

Unconventional therapies (UTs) are therapies not usually provided by Canadian physicians or other conventionally trained health care providers. Examples of common UTs available in Canada are herbal preparations, reflexology, acupuncture and traditional Chinese medicine. UTs may be used along with conventional therapies (complementary) or instead of conventional therapies (alternative). Surveys have shown that many Canadians use UTs, usually as complementary therapies, for a wide range of diseases and conditions. Reliable information about UTs is often difficult to find. Your doctor may be unable to give you specific advice or recommendations, since UTs are often not in a physician''s area of expertise. However, he or she will usually be able to provide some general advice and help supervise your progress. For your own health and safety, it is important to keep your doctor informed of the choices you make. This document is intended to (a) provide you with questions to consider when making your treatment choices, (b) help you find information about UTs, (c) help you decide whether a specific UT is right for you, and (d) provide tips to help you evaluate the information you find.     

A short guide to technology development in cell biology

New technologies drive progress in many research fields, including cell biology. Much of technological innovation comes from “bottom-up” efforts by individual students and postdocs. However, technology development can be challenging, and a successful outcome depends on many factors. This article outlines some considerations that are important when embarking on a technology development project. Despite the challenges, developing a new technology can be extremely rewarding and could lead to a lasting impact in a given field.As is true for many fields of research, cell biology has always been propelled forward by technological innovations (Botstein, 2010). Thanks to these advances we now have access to microscopes and other equipment with exquisite resolution and sensitivity, a variety of methods to track and quantify biological molecules, and many ingenious tools to manipulate genes, molecules, organelles, and cells. In addition, we have hardware and software that enable us to analyze our data, and build models of cells and their components.Naturally, even today’s technologies have limitations, and hence there is always need for improvements and for completely novel approaches that create new opportunities. Cell biology is one of the research areas with many chances for individual young scientists to invent and develop such new technologies. Numerous recent examples illustrate that such “bottom-up” efforts can be highly successful across all areas in cell biology; e.g., as a handy vector for RNA interference (Brummelkamp et al., 2002); as methods for visualization of protein–protein or protein–DNA interactions (Roux et al., 2012; Kind et al., 2013); as tools to study chromatin (van Steensel et al., 2001), ribonucleoprotein complexes (Ule et al., 2003), or translation (Ingolia et al., 2009); or as tags for sensitive protein detection (Tanenbaum et al., 2014), just to name a few examples.As a student or postdoc, you may similarly conceive an idea for a new method or tool. Usually this idea is inspired by a biological question that you are trying to address in your ongoing research project. You might then also realize that the new method, at least on paper, may have additional applications. Yet, the development of a new technique typically requires a substantial effort. Should you halt or delay your ongoing research and embark on the development of this new technique? And if so, what is the best strategy to minimize the risks and maximize the chance of success? How do you get the most out of the investment that it takes to develop the method? Here I will discuss some issues that students and postdocs might want to consider when venturing into the development of a new technique.

To develop or not to develop

Development of a new technique can take one to five years of full-time effort, and hence can be a risky endeavor for a young scientist. The decision to start such a project therefore requires careful weighing of the pros and cons (see text box). In essence, there are four main considerations.

Points to consider before starting to develop a new technology.

•Literature search: Does a similar technology already exist? Is there published evidence for or against its feasibility?•How much time and effort will it take?•What is the chance of success?•Are you in the right environment to develop the technology?•Are simple assays available for testing and optimization?•How important are the biological questions that can be addressed?•How broadly applicable will the technology be?•What are the advantages compared with existing methods?•Is the timing right (will there be substantial interest in the technology)?•Is there potential for future applications/modifications that will further enhance the technology?•How easy will it be for other researchers to use the technology?First, conduct a thorough literature survey to ensure that the method has not been developed by others already, and to search for indications that the method may or may not work. The second consideration is the potential impact of the new technology. Impact is often difficult to predict, but it is linked to how broadly applicable the technology will be. Will the new technology only provide an answer to your specific biological question, or will it be more widely applicable? It may be helpful to ask: how many other scientists will be interested in using the technology, or at least will profit substantially from the resulting biological data or knowledge? If the answer is “about five,” then the impact will likely be low; if the answer is “possibly hundreds,” then it will certainly be worth the investment. This potential impact must be balanced against the third consideration, which is the estimated amount of time and effort it takes to develop the technology. The fourth major consideration is: What is the chance that my technique will actually work and what is the risk of failure? There is no general answer to this question, but below I will outline strategies to reduce the risk of failure and minimize the associated loss of time and effort. For this I will consider the common phases of technology development (Fig. 1).Open in a separate windowFigure 1.Flow diagram showing the typical phases of technology development.

Quick proof-of-principle

An adage that is often heard in the biotechnology industry is “fail fast.” It is OK if a project turns out to be unsuccessful, as long as the failure becomes obvious soon after the start. This way the lost investment will be minimal. In an academic setting, it may also be good to prevent finding yourself empty-handed after years of work. As a rule of thumb, I suggest that one should aim to obtain a basic proof-of-principle within approximately four months of full-time work. If after this period there still is no indication that the method may eventually work, then it may be wise to terminate the project, because further efforts are then also likely to be too time-consuming. It is thus advisable to schedule a “continue/terminate” decision point about four months after the start of the project—and stick to it. Note that at this stage the proof-of-principle evidence may be rudimentary, but it is crucial that it is convincing enough to be a firm basis for the next step: optimization.

Optimization cycles

Obtaining the first proof-of-principle evidence is a reason to celebrate, but usually it is still a long way toward a robust, generally applicable method. Careful optimization is required, through iterations of systematic tuning of parameters and testing of the performance. This can be the most time-consuming phase of technology development. To keep the cycle time of the iterative optimizations short, it is essential that a quick, easy readout is chosen. This readout should be based on a simple assay that ideally requires no more than 1–2 d. It is important that the required equipment is readily accessible; for example, if for each iteration you have to wait for several weeks to get access to an overbooked shared FACS or sequencing machine, or if you depend on the goodwill of a distant collaborator who has many other things on his mind, then the optimization process will be slow and frustrating. If your technology consists of a lengthy protocol with multiple steps, try to optimize each step individually (separated from the rest of the protocol), and include good positive and negative controls.Remember that statistical analysis is your ally: it is a tool to distinguish probable signals from random noise and thus enables you to make rational decisions in the optimization process (did condition A really yield better results than condition B?). Assays with quantitative readouts are easier to analyze statistically and are therefore preferable.

Version 1.0: Reaping the first biological insights

During the optimization process it is helpful to define an endpoint that will result in “version 1.0” of the technology. Typically this is when the technology is ready to address its first interesting biological question. Once you have reached this point, it may be useful to temporarily refrain from further optimization of the technology, and focus on applying it to this biological question. This has two purposes. First, it subjects the technology to a real-life test that may expose some of its shortcomings, which then need to be addressed in further optimization cycles. Second, it may yield biological data that illustrates the usefulness of the technology, which may inspire other scientists to adopt the method. If you are based in a strictly technology-oriented laboratory, collaboration with a colleague who is an expert in the biological system at hand may expedite this phase and help to work out bugs in the methodology.If version 1.0 performs well in this biological test, it may be time to publish the method. For senior postdocs, this may also be a good moment to start your own laboratory. A new technology is usually a perfect basis for such a step.

Disseminating and leveraging the technology

When, upon publication, other scientists adopt your new technology, they will often implement improvements and new applications, which makes the technology attractive to yet more scientists. This snowball effect is one of the hallmarks of a high-impact technology. An extreme example is the recently developed CRISPR–Cas9 technology (Doudna and Charpentier, 2014), for which improvements and new applications are currently reported almost on a weekly basis. What can you do to get such a snowball rolling?First, it helps to publish the new technology in a widely read or Open Access journal, to present it at conferences, and to initiate collaborations in order to reach a broad group of potential users. Second, the threshold for others to use the new technology must be as low as possible. Thus, implementation of the technology must be simple, and users must have easy access to detailed protocols. A website with troubleshooting advice, answers to frequently asked questions, and (if applicable) software for download will also help. Depending on the complexity of the technology, it may be worth considering whether to organize hands-on training, perhaps in the form of a short course. This may seem like a big investment, but it can substantially contribute to the snowball effect.Third, materials and software required for the technology should be readily available. Technology transfer offices of research institutes often insist on the signing of a material transfer agreement (MTA) before materials such as plasmids can be shared. But all too often this leads to a substantial administrative burden and delays of weeks or even months. Free “no-strings-attached” sharing of reagents is often the best way to promote your technology—and scientific progress in general.

Patents and the commercial route

Before publication of the technology, you may consider protecting the intellectual property by filing a patent application. Most academic institutes do this, but often the associated costs are high and the ultimate profits uncertain, in part because it can be difficult to enforce protection of a patented technology (how do you prove that your technology was used by someone else?). That said, some technologies or associated materials may be more effectively scaled up and disseminated through a commercial route than via purely academic channels. Specific companies may have distribution infrastructure or technical expertise that is hard to match in an academic laboratory. Founding your own company may also be a way to give the technology more leverage, as it provides access to funds not available in an academic setting. In these cases, timely filing of a patent application may be essential. Note that in certain countries one cannot apply for a patent once the technology has been publicly disclosed (e.g., at a conference).

Competing technologies

Often different technologies for the same purpose are invented independently and more or less simultaneously. It is therefore quite likely that sooner or later an alternative technology emerges in the literature, or appears on the commercial market. This is sometimes referred to as “competing technology,” but in an academic setting this is somewhat of a misnomer, as solid science requires multiple independent methods to cross-validate results. Moreover, it is extremely rare that two independent technologies cover exactly the same spectrum of applications. For example, one technology may have a higher resolution, but the other may be superior in sensitivity. The sudden emergence of a competing technology can however have strategic consequences, and it is important to carefully define the advantages of your technology and focus on these strengths.

A bright future for technology development

New technologies generally consist of a new combination of available technologies, or apply newly discovered fundamental principles. Because the pool of available knowledge and tools continues to expand, the opportunities to devise and test new methods will only improve. This is further facilitated by the increasing quality of basic methods and tools to build on. Thus, there is a bright future for technology development. With a carefully designed strategy, the risks associated with such efforts can be minimized and the overall impact maximized. In the end, it is extremely gratifying to apply a “home-grown” technology to exciting biological questions, and to see other laboratories use it.     

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.”