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.     

Work life balance?

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

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

Borrowed robes

Should scientists indulge their fantasies by writing fiction? Subject Categories: Careers, Economics, Law & Politics, History & Philosophy of Science

Like a substantial fraction of the literate population, I have a collection of unpublished novels in the drawer. Six of them in fact. Some of them were composed in barely more than a week, and others I have been struggling to complete for over 10 years: so maybe it is more accurate to say five and a half. Anyhow, most of them are good to go, give or take a bit of editorial redlining. Or, as my helpful EMBO editor would say, the removal of thousands of unnecessary adverbs and dubiously positioned commas.What do I write about and why? My style is not unique but rather particular. I write fiction in the style of non‐fiction. My subject matter is somewhere in the general realms of science fiction, alternate history and political drama. Putting these ingredients together, and taking account of my purported day job as a serious scientist, it is easy to see why my fictional work is potentially subversive—which is one reason why I have been rather reluctant thus far to let it out of the drawer. At the very least, I should take pains to conceal my identity, lest it corrupts perceptions of my scientific work. Even if I regularly tell my students not to believe everything they read, it would impose far too great a burden on them if they came to question my peer‐reviewed articles purely on the basis of untrue statements published in my name, spoken by jaded politicians, washed‐up academics or over‐credulous journalists. Even if they are imaginary. Real journalists are theoretically bound by strict rules of conduct. But imaginary ones can do whatever they like.Today, I noticed a passage in one of these unpublished works that is clearly written in the style of a young William Shakespeare, dealing with a subject matter that fits neatly into one of his most famous plays. In fact, the illusion was such that I was sure I must have lifted the passage from the play in question and set about searching for the quote, which I then could and should cite. Yet, all Internet searches failed to find any match. The character in whose mouth I placed the words was depicted as being in a delirious state where the boundaries of fact and fiction in his life were already blurred; borrowed identities being one of the themes of the entire novel and arguably of my entire oeuvre. But am I guilty here of plagiarism or poetry, in adopting the borrowed identity of my national playwright?In another work, I lay great emphasis on the damaging role of mitochondrial reactive oxygen species (ROS) as the cause of biological ageing. I have even grafted this explanation onto a thinly disguised version of one of my most valued colleagues. Although there is some support for such a hypothesis from real science, including some papers that I have myself co‐authored, it is also a dangerously broad generalization that leads easily into wrong turnings and misconstructions—let alone questionable policies and diet advice. But, by advancing this misleading and overly simplistic idea in print, have I potentially damaged not only my own reputation, but that of other scientists whom I respect? Even if the author’s identity remains hidden.In one novel, I fantasize that nuclear weapons, whilst they do undoubtedly exist, have in fact been engineered by their inventors so as never actually to work, thus preventing their possible misuse by vainglorious or lunatic politicians unconcerned with the loss of millions of lives and planetary ruin. But if any insane national leader—of which there are unfortunately far too many—would actually come to believe that my fiction in the style of non‐fiction were true, they might indeed risk the outbreak of nuclear war by starting a conventional one in order to secure their strategic goals.Elsewhere, I vindicate one author of published claims that were manifestly based on falsified data, asserting him to have instead been the victim of a conspiracy launched to protect the family of an otherwise much respected American President. None of which is remotely true. Or at least there is no actual evidence supporting my ridiculous account.I have great fun writing fiction of this kind. It is both liberating and relaxing to be able to ignore facts and the results of real experiments and just invent or distort them to suit an imaginary scenario. In an age when the media and real politicians have no qualms about propagating equally outrageous “alternative facts”, I can at least plead innocent by pointing out that my lies are deliberate and labelled as such, even if people might choose to believe them.In a further twist, the blurb I have written to describe my latest work characterizes it as the “semi‐fictionalized” biography of a real person, who was, in fact, a distant relative of mine. But if it is semi‐fictionalized, which bits are true and which are made up? Maybe almost the whole thing is invented? Or maybe 99% of it is based on demonstrable facts? Maybe the subject himself concocted his own life story and somehow planted it in falsified documents and newspaper articles to give it an air of truth. Or maybe the assertion that the story is semi‐fictionalized is itself a fictional device, that is, a lie. Perhaps the central character never existed at all.It is true (sic) that the most powerful fiction is grounded in fact—if something is plausible, it is all the more demanding of our attention. And, it can point the way to truths that are not revealed by a simple catalogue of factual information, such as in a scientific report.But I have already said too much: if any of my novels ever do find their way into print, and should you chance to read them, I will be instantly unmasked. So maybe I’ll have to slot in something else in place of my pseudo‐Shakespearean verse, mitochondrial ROS hypothesis, defunct weapons of mass destruction and manipulated data manipulation.     

Academic motherhood – what happens when you can't make it happen?

We need more openness about age‐related infertility as it is a particular risk for many female scientists in academia who feel that they have to delay having children. Subject Categories: S&S: Careers & Training, Genetics, Gene Therapy & Genetic Disease

Balancing motherhood and a career in academic research is a formidable challenge, and there is substantial literature available on the many difficulties that scientists and mothers face (Kamerlin, 2016). Unsurprisingly, these challenges are very off‐putting for many female scientists, causing us to keep delaying motherhood while pursuing our hypercompetitive academic careers with arguments “I’ll wait until I have a faculty position”, “I’ll wait until I have tenure”, and “I’ll wait until I’m a full professor”. The problem is that we frequently end up postponing getting children based on this logic until the choice is no longer ours: Fertility unfortunately does decline rapidly over the age of 35, notwithstanding other potential causes of infertility.This column is therefore not about the challenges of motherhood itself, but rather another situation frequently faced by women in academia, and one that is still not discussed openly: What if you want to have children and cannot, either because biology is not on your side, or because you waited too long, or both? My inspiration for writing this article is a combination of my own experiences battling infertility in my path to motherhood, and an excellent piece by Dr. Arghavan Salles for Time Magazine, outlining the difficulties she faced having spent her most fertile years training to be a surgeon, just to find out that it might be too late for motherhood when she came out the other side of her training (Salles, 2019). Unfortunately, as academic work models remain unsupportive of parenthood, despite significant improvements, this is not a problem faced only by physicians, but also one faced by both myself and many other women I have spoken to.I want to start by sharing my own story, because it is a bit more unusual. I have a very rare (~ 1 in 125,000 in women (Laitinen et al, 2011)) congenital endocrine disorder, Kallmann syndrome (KS) (Boehm et al, 2015); as a result, my body is unable to produce its own sex hormones and I don’t have a natural cycle. It doesn’t take much background in science to realize that this has a major negative impact on my fertility—individuals with KS can typically only conceive with the help of fertility treatment. It took me a long time to get a correct diagnosis, but even before that, in my twenties, I was being told that it is extremely unlikely I will ever have biological children. I didn’t realize back then that KS in women is a very treatable form of infertility, and that fertility treatments are progressing forward in leaps and bounds. As I was also adamant that I didn’t even want to be a mother but rather focus on my career, this was not something that caused me too much consternation at the time.In parallel, like Dr. Salles, I spent my most fertile years chasing the academic career path and kept finding—in my mind—good reasons to postpone even trying for a child. There is really never a good time to have a baby in academia (I tell any of my junior colleagues who ask to not plan their families around “if only X…” because there will always be a new X). Like many, I naïvely believed that in vitro fertilization (IVF) would be the magic bullet that can solve all my fertility problems. I accordingly thought it safe to pursue first a faculty position, then tenure, then a full professorship, as I will have to have fertility treatment anyhow. In my late twenties, my doctors suggested that I consider fertility preservation, for example, through egg freezing. At the time, however, the technology was both extravagantly expensive and unreliable and I brushed it off as unnecessary: when the time comes, I would just do IVF. In reality, the IVF success rates for women in their mid‐to‐late 30s are typically only ~ 40% per egg retrieval, and this only gets worse with age, something many women are not aware of when planning parenthood and careers. It is also an extremely strenuous process both physically and emotionally, as one is exposed to massive doses of hormones, multiple daily injections, tremendous financial cost, and general worries about whether it will work or not.Then reality hit. What I believed would be an easy journey turned out to be extremely challenging, and took almost three years, seven rounds of treatment, and two late pregnancy losses. While the driving factor for my infertility remained my endocrine disorder, my age played an increasing role in problems responding to treatment, and it was very nearly too late for me, despite being younger than 40. Despite these challenges, we are among the lucky ones and there are many others who are not.I am generally a very open person, and as I started the IVF process, I talked freely about this with female colleagues. Because I was open about my own predicament, colleagues from across the world, who had never mentioned it to me before, opened up and told me their own children were conceived through IVF. However, many colleagues also shared stories of trying, and how they are for various—not infrequently age‐related—reasons unable to have children, even after fertility treatment. These experiences are so common in academia, much more than you could ever imagine, but because of the societal taboos that still surround infertility and pregnancy and infant loss, they are not discussed openly. This means that many academic women are unprepared for the challenges surrounding infertility, particularly with advanced age. In addition, the silence surrounding this issue means that women lose out on what would have otherwise been a natural support network when facing a challenging situation, which can make you feel tremendously alone.There is no right or wrong in family planning decisions, and having children young, delaying having children or deciding to not have children at all are all equally valid choices. However, we do need more openness about the challenges of infertility, and we need to bring this discussion out of the shadows. My goal with this essay is to contribute to breaking the silence, so that academics of both genders can make informed choices, whether about the timing of when to build a family or about exploring fertility preservation—which in itself is not a guaranteed insurance policy—as relevant to their personal choices. Ultimately, we need an academic system that is supportive of all forms of family choices, and one that creates an environment compatible with parenthood so that so many academics do not feel pressured to delay parenthood until it might be too late.     

University campuses need people in them

As COVID‐19 has turned universities into ghost towns, David Smith cannot wait for the day when his campus fills with life again.

In the novel Fool’s Fate, Robin Hobb writes: “Home is people. Not a place. If you go back there after the people are gone, then all you can see is what is not there anymore.” I feel the same about university campuses.In late August 2020, after months of working from home, I returned to the campus of Western University where I am an associate professor of biology. It was supposed to be a short visit, in and out to grab some notebooks and an external monitor. But when I unlocked the office door and sat in that old wooden desk chair amongst the calm clutter of my workspace, I did not get up for a good two hours. I was comforted by the familiarity of my bookshelves, photographs, and professorial memorabilia, including a large bust of Darwin and a giant whale’s tooth. How I missed this place. And apart from two dead plants and a generous layer of dust, everything was as it should be.Outside my office was a different story. The water fountains were covered up with caution tape. Bright purple floor markings indicated the correct side of the hallway to walk down. Main offices, libraries, and canteens were closed. Large signs on all major doorways reiterated the social distancing policies. And apart from the odd security officer or grounds person, the campus was eerily empty. Nevertheless, I decided that for as long as the university remained open, I would keep coming to my office for a few hours a day, mainly to read and write without the cacophonic company of a toddler, but also to bring back some semblance of normalcy to my work life.The plan started off well. Each morning I would pack a large lunch, walk to campus and enjoy a few uninterrupted hours of academic productivity. But the stillness and emptiness of the university began to weigh on me. I could swear the fluorescent lights in my office were buzzing more loudly than before. Was the central air system always this rickety? After an hour of writing, I would take a quick walk around the department to clear my mind and see if anyone else was in. On my fifth day, I finally found someone: Vera’s office door was propped open! I quickly checked that my mask was on correctly and poked my head around. Small talk—glorious small talk—ensued for at least fifteen minutes. I had forgotten how nice it was to chat with a colleague in person. I went back to my office refreshed and put in another hour of good work. The next day, the building was deserted again. Not a sliver of light beneath Vera’s or any other door.I hoped that maybe once classes resumed in mid‐September, some vitality would return to campus. But, of course, nearly all of the classes were online and students and staff stayed home. Sometimes on my departmental wanderings, I would go into one of the large lecture halls and just stand at the podium. Once I even plugged my laptop into the AV system and practiced a presentation that I was preparing for an upcoming Zoom talk. As strange as it sounds, speaking to hundreds of lifeless seats in that old, stuffy hall felt more natural than talking to a grid of black boxes with nametags on my computer screen.As the weeks wore on and my visits to campus continued, a deep melancholy slowly took hold of me. I would spend hours on seemingly simple tasks, like tidying my office or answering emails. Harder tasks, such as writing a paper or developing a new lecture, felt insurmountable. I started leaving everything to the last minute or missing deadlines completely, which is unlike me. It felt as if my mood was somehow mirroring that of the vacant classrooms and buildings surrounding me. They, too, were paying the price of the pandemic.I have spent most of my life on college campuses. My father was a chemistry professor and often took me to work with him when I was a small child. My first daycare was at a university. As an adolescent and teenager, I would go to the local college most days for after‐school clubs. I learnt to swim at a university pool, became a senior boys 1500 m running champion on a university track, and discovered my love of mountain biking and cross‐country skiing on university trails. I met my closest friends in university residences. And my passion for science and writing was fostered in university classrooms. I love universities. I love what they represent: places of learning, scholarship, and development. I love the palpable emotions that they emit, from the endless possibilities of the first week of classes to the anxieties and sense of completion during final examinations. Most of all, I love the people that make up universities, their eclectic mix of personalities, backgrounds, ages, and beliefs. This might sound strange, but when I go on vacation, I visit universities elsewhere. I will spend an entire afternoon roaming around a campus, reading in the library, or sitting on a bench watching people come and go. This may be why I am so sad that my current institute sits unoccupied, at least in the physical sense. Ironically, enrollment is up. My department has more new undergraduate students than it has had in years.The other day on my walk home from work I ran into a colleague. He described to me how he has been working hard to get the upcoming introductory genetics course online, especially given the increase in students (there are more than 1200 currently enrolled in the course). I said, “You must be looking forward to the end of this crisis when we can start teaching in‐person again.” His response has had a lasting effect on me. “I’m not so sure things will go back to the way they were,” he said. “A lot of students are enjoying online learning—or are at least finding it convenient and cost‐effective. Many are saving money by living at home and by not having to bus into campus every day and buy overpriced food. They like being able to watch the recorded lectures on their own schedule and at their own speed. Even after the current crisis ends, I think there be will be a strong push for continued online learning.” “You might be right,” I said, “but I sure hope not.”When we parted ways, I felt even more downtrodden. I reminded myself that I was lucky to have a great job and that I needed to be adaptable. If the future is online learning, so be it. I can become a connoisseur of Camtasia. I can learn to be creative and engaging over Zoom. I can master those microphone and camera settings. But I could not help thinking this is not what I signed up for. When the pandemic is over, I do not want to exist in a cyber campus with online students and online colleagues. I do not want my home to be a lecture hall. I want brick and mortar and real bums in real seats. I want to stand in line for 20 minutes outside the student union building for lukewarm coffee. I want to waste precious time walking to meetings and making small talk in the corridors. I want the thing that I fell in love with. Until COVID‐19 is defeated, we need to stay vigilant. But when the war is won, will university campuses return to being physical gathering points for learning, engagement and community building or virtual concepts in an online learning space? Whatever the answer, I know that if you are looking for Associate Professor David R. Smith, you will find him holding out in the Biological and Geological Sciences Building, room 3028. The hand‐written sign on the door will say, “Going down with the ship.”     

In conversation with the Chief Editor

An interview with Facundo D Batista, The EMBO Journal new Editor‐in‐Chief.

An interview with Facundo D. Batista, The EMBO Journal new Chief Editor. Facundo D. Batista has shaped our understanding of the molecular and cellular biology of B‐cell activation. In 2016, he relocated his lab to Massachusetts General Hospital/M.I.T./Harvard’s Ragon Institute to explore the translational potential of two decades of basic research in B‐cell biology. The interview was conducted by Thiago Carvalho. Thiago Carvalho (TC): What inspired you to pursue a career in science? Facundo D Batista (FDB): I was very inspired by my undergraduate course on molecular biology at the University of Buenos Aires. The course was given for the first time, and we were taught the basic techniques of handling DNA, producing insulin, and so forth. Two professors in the course, Daniel Goldstein and Alberto Kornblihtt, really primed us to open our horizons and encouraged training in centers of excellence abroad. I did not speak any English at all, and applying to graduate school in the United States and doing the GRE was impossible for me. I would not have passed. Then, an opportunity to go to Italy and get experience in institutes that could provide me with better training came up. If I recall correctly, we were the first generation of Argentinian biology graduates—myself, Pablo Pomposiello, and many others—that left Argentina looking for a PhD. In general, people would try for a postdoc.I applied to a PhD program in Italy. I went with an open ticket for a year. If I had not passed the ICGEB/SISSA (Trieste) examination, I had three thousand dollars to travel around, and then I would go back to Argentina. I had never been in Europe before. So, for me it was an experience. What happened was that I was very lucky to be admitted in probably the first generation of this new institution, the International Centre for Genetic Engineering and Biotechnology in Italy. In three years, I finished my PhD, and then, to be honest, as an Argentinian in Europe, I did not have many postdoctoral funding opportunities either. TC: How did you move from Trieste to Cambridge’s Laboratory of Molecular Biology? FDB: I found Michael Neuberger’s laboratory to be very appealing, and I wrote to Michael. He replied to me, in a letter that I still keep, that—if I was able to obtain a fellowship—he would take me in his laboratory. A wonderful thing about EMBO was that it would recognize the country where you did your PhD when considering postdoctoral fellowship applications, giving me access to this important funding support. ¹ It was the very early days of diversity—the notion that people could be eligible for support based not only on their nationality, but also on their “scientific nationality”. It gave me a unique opportunity. TC: It was also an opportunity to meet another source of inspiration for you, César Milstein FDB: César was not well at the time, he had heart problems. But I met him, and I felt very close because Michael was working with César, and he worked next door. For me, walking in those corridors with César Milstein and several other Nobel Prize winners—you know, Aaron Klug and Max Perutz—it was a dream. I could not believe that you could have lunch with these wonderful people, and they would come and talk to you, not as Dr. Klug or Dr. Milstein, but they would be César, Aaron, and Max. That for me was totally mind‐changing, together with my relationship with Michael, whom I love. They completely changed my perspective on science. TC: What do you remember most about Michael Neuberger as a mentor? FDB: What was incredible about Michael was his clarity. You would present any biological problem to him, and he would crystallize in one sentence what the real question behind it was. He was amazing. Michael would enter into a state of thinking where he would stop looking at you and would start looking up at a wall and would start to concentrate for those 10, 20 minutes that you’d explain the problem. Then, he would come up with critical questions and he would be critical to the bones. I think that that is something that science has lost these days. I think that this notion of going deep into critically asking the right scientific questions has been lost as a tradition. It is something that I try to transmit to my postdocs and PhD students: Scientific criticism is not about personal or emotional evaluation. It is really about trying to nail down what the question is and how a project develops. I think that is what I remember most of Michael, his commitment to the people that worked with him and who surrounded him and that deep thinking and constant challenging about what is the next step. TC: In 2002, you started your laboratory at the London Research Institute FDB: I was at one stage considering staying at the LMB with my independent lab, and César and Michael were very supportive of that. But then came the opportunity to join the LRI—which at the time was still the ICRF. I was the last employee recruited (to the ICRF), and it was wonderful. The notion of changing environments again, changing colleagues. The LMB was not an immunology institute. It was a general research institute and the ICRF at that time was similar, with very little immunology. I have always valued the whole spectrum of biology from mathematical modeling to quantitative biology to biochemistry to technological inputs, to development, and so forth. TC: Your LRI laboratory revealed entirely new aspects of the molecular and cellular biology of B lymphocytes—one was the existence of organized membrane structures reminiscent of the immunological synapse first described in T cells that were crucial for activation. What are the implications of the immunological synapse for B‐cell function? FDB: It was a concept that was resisted by the B‐cell field. The notion at the time was that B cells would get activated by soluble antigens. But if you think about it, that does not make any sense. You will never reach a physiological concentration of a ligand that will allow you to engage a receptor in vivo at a low affinity. So in order to reach that concentration, you need to aggregate antigen on the surface of other cells first. And that makes the whole process much more efficient. It not only localizes the process into lymph nodes or spleens, but it also allows focusing the response into what the arrangement of a membrane is. I was not the first—the notion that antigens are on follicular dendritic cells was well‐established by early experiments. But I think our work transformed the field. A lot of laboratories have incorporated the notion that stimulating cells at the level of membranes changes the way that receptors perceive signals. This does not apply only to the B‐cell receptor, it applies to chemokines too, many of them are also coating the surface of other cells and that helps guide the signals that cells receive.I think that it is an important concept that is likely to be applicable to vaccines. There are several papers now showing that helping to aggregate antigens on the surface of macrophages or dendritic cells makes antigens more potent by driving them more efficiently into where they are used in follicles and lymph nodes. TC: What prompted your pivot to translational research? FDB: I had learned a lot about basic principles of B‐cell biology and antibody responses, but on model antigens. I felt at the time that translating that into humans and trying to understand how vaccines could be improved was an important step. I always like to recognize mentors or people who influenced me and one person who really influenced me in this thinking was Dennis Burton at Scripps. He was very early to incorporate into his HIV vaccine and antibody research people like me or Michelle Nussenzweig that were coming from basic B‐cell immunology to try to help to think about how vaccines can be improved. I decided to take a risk. I left a tenured, core‐funded position at the best institution in Europe to lead the Ragon Institute with Bruce Walker—I am the Associate Director and he is the Director—and brought my years of expertise at the ICGEB, LMB, LRI, and CRICK to a unique environment that is based on translational research. There is the incredible ecosystem of Harvard, MIT, and MGH, and the notion is to incorporate technologies and to incorporate immunology to tackle incredible challenges, like COVID‐19 is today. TC: Are there any major initiatives that you plan to focus on at The EMBO Journal? FDB: One of the things that I would really like to do is to involve the younger generations in the journal. I think that we have an opportunity for direct “translation”. I mean, EMBO has EMBO postdoctoral fellowships and EMBO young investigators, involving early career European scientists, but also scientists across the globe. We are discussing initiatives like, for example, inviting postdocs from different laboratories to present at the editorial meetings. The EMBO Journal has an open‐door policy in terms of people wanting to participate in the editorial meetings.I think that we have amazing scientists around the world that can really bring new views as to where the journal should be going. I feel strongly about that and about keeping a real sense of diversity in the journal, in terms of fields, in terms of gender, in terms of race, in getting people involved from Brazil, getting people involved from China, getting people involved from Japan, from across the globe. EMBO is no longer a European journal. EMBO is a journal whose office faces Europe, but it has a global outlook. TC: Early in their career, many researchers do not feel comfortable engaging with editors FDB: I sent one of my first papers as an independent P.I. to EMBO. That paper was editorially rejected. I replied to that rejection, saying that EMBO should stop publishing just biochemistry, and that they needed to appreciate the importance of quantitative cell biology. The paper was ultimately sent to review and accepted. What was also very positive was that a later review of the scope of The EMBO Journal came to a similar conclusion. That resulted in my appointment to the editorial advisory board of The EMBO Journal (I was not an EMBO member at the time). The positive message is that the journal very much welcomed receiving feedback. That was what made me like the journal. I felt that the journal was ready to listen, to change.This is not my journal. It is the community’s journal. I am just playing a role, putting in some time and effort. There are a lot of things that I do not see and other young people could see, and I am looking for inspiration there, to listen and translate those things into good policies for the journal. I think that this is important and I think that this is at the basis of what I want to be as a chief editor.     

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.”     

After the year of the dumpster fire

2020 has been one of the craziest and strangest years we have lived through. Now that it’s over, it’s an opportunity to show gratitude for all the good things. Subject Categories: S&S: History & Philosophy of Science

I moved to New York City the year of the attacks on September 11, 2001, one of the bleakest moments in the history of the United States. I was also in New York City when Superstorm Sandy hit in 2012. Luckily, much fewer people died due to the storm, but it was incredibly disruptive to many scientists in the affected area—my laboratory had to move four times over a period of 6 years in the storm’s aftermath. These were awful, tragic events, but 2020 may go down in the record books as one of the most stressful and crazy years in modern times. Not to be outdone, 2021 has started terribly as well with COVID‐19 still ravaging the world and an attack on the US Capitol, something I thought I’d never see in my lifetime. The unnecessary deaths and the damage to America’s “House of the People” were heartbreaking.While these events were surely awful, nothing will be as crushing as the deaths of family members, close friends, and the children of friends; perhaps, it is these experiences—and the death of a beloved dog—that prepared me for this year and made me grateful, maybe even more than usual, for what I have. But in the age of a pandemic, what am I particularly grateful for?I''m ridiculously grateful to have a job, a roof over my head, and food security. The older I get, the more I see illness and injury affect my colleagues, family, and friends, I increasingly appreciate my good health. I am grateful for Zoom (no, I have no investment in Zoom)—not for the innumerable seminars or meetings I have attended, but for the happy hours that helped to keep me sane during the lockdown. Some of these were with my laboratory, others with friends or colleagues, sometimes spread over nine time zones. Speaking of which, I’m also grateful for getting a more powerful router for the home office.I''m immeasurably grateful to be a scientist, as it allows me to satisfy my curiosity. While not a year‐round activity, it is immensely gratifying to be able to go to my laboratory, set up experiments, and watch the results coming in. Teaching and learning from students is an incredible privilege and educating the next generation of scientists how to set up a PCR or run a protein gel can, as a well‐known lifestyle guru might say, spark serious joy. For this reason, I’m eternally grateful to my trainees; their endless curiosity, persistence, and energy makes showing up to the laboratory a pleasure. My dear friend Randy Hampton recently told me he received a student evaluation, thanking him for telling his virtually taught class that the opportunity to educate and to be educated is something worth being grateful for, a sentiment I passed onto a group of students I taught this past fall. I believe they, too, were grateful.While all of the above things focus on my own life, there are much broader things. For one, I am so grateful to all of those around the globe who wear masks and keep their distance and thereby keep themselves and others safe. I am grateful for the election of an American president who proudly wears a mask—often quite stylishly with his trademark Ray‐Ban Aviators—and has made fighting the COVID‐19 pandemic his top priority. President Biden''s decision to ramp up vaccine production and distribution, along with his federal mask mandate, will save lives, hopefully not just in the United States but worldwide.This Gen‐X‐er is also especially grateful to the citizens of Generations Y and Z around the world for fighting for social justice; I am hopeful that the Black Lives Matter movement has got traction and that we may finally see real change in how communities of color are treated. I have been heartened to see that in my adopted home state of New York, our local politicians ensure that communities that have been historically underserved are prioritized for COVID‐19 testing and vaccinations. Along these lines, I am also incredibly encouraged by the election of the first woman who also happens to be of African and Asian heritage to the office of vice president. Times are a changin''...While it is difficult to choose one, top thing to be grateful for, I would personally go for science. I am stoked that, faced with a global crisis, science came to the rescue, as it often has in the past. If I had to find a silver lining in COVID‐19—albeit it would be for the darkest of clouds—I am grateful for all of our colleagues, who despite their usual arguing, quickly and effectively developed tests, provided advice, epidemiological data and a better understanding of the virus and its mode of infection, and ultimately developed therapies and vaccines to save lives. The same can be said for the biotech and pharmaceutical industry that, notwithstanding its often‐noted faults, has been instrumental in developing, testing and mass‐producing efficient and safe vaccines in blistering, record time. Needless to say, I have also much gratitude to all of the scientists and regulators at the FDA and elsewhere who work hard to make life as we once knew it come back to us, hopefully in the near future.Once again, thank you for everything, Science.     

Alcodemia: are we training our students to be great thinkers or great drinkers?

Academia has fostered an unhealthy relationship with alcohol that has an undeniable impact on the health and behaviour of students and staff. Subject Categories: S&S: History & Philosophy of Science, Chemical Biology, S&S: Ethics

University life has a lot to offer. And, for better or worse, much of it goes hand in hand with a bottle. Believe it or not, I was a bit of teetotaler in my undergraduate days but quickly made up for it in graduate school, where each celebration included inebriation. Indeed, my initial tour of the laboratory I eventually worked in included a refreshing visit to the grad club. Orientation week ended with a marathon beer blitz at a nightclub. The semester’s first invited seminar speaker was welcomed with the sounds of loose change, ice buckets and the clickity‐clack of organic microbrews being opened. Our inaugural genome evolution journal club was such a success that we vowed to spill even more red wine onto our notebooks the following week. In hindsight, I should have realized at this early stage in my studies that I was fostering an unhealthy and unsustainable relationship between biology and booze. Unfortunately, my post‐graduate education in alcohol didn’t stop there.Like many keen students, I arrived at my first scientific conference with a belly full of nerves and a fistful of drink tickets, which I quickly put to good use at the poster session. The successful completion of my PhD proposal assessment was met with pats on the back as I was swiftly marched off to a local pub with no chance of escape. My first peer‐reviewed paper literally arrived with a pop as Champagne was generously poured into plastic cups for the entire laboratory group. My failures, too, were greeted with a liberal dose of ethanol. “Sorry you came up short on that scholarship application, Smitty. It’s nothing a little weapons‐grade Chianti won’t cure.” “That experiment failed again! Come on, let me buy you a lunchtime martini to make up for it.” Soon I learnt that every academic event, achievement or ailment, no matter how big or small, could be appropriately paired with beer, wine or spirit. Missing from the menu were two crucial ingredients for any burgeoning researcher: moderation and mindfulness.But it was the older vintages that really inspired me – the legendary drinking escapades of my scientific mentors, advisors and idols. The tale of professor so‐and‐so who at that epic meeting in 1993 polished off an entire magnum of rosé at dinner and then went on to deliver among the greatest keynote lectures on record at 9 am the following morning. That celebrated chaired researcher who kept the single malt next to the pipette tips for quick and easy access. The grizzled evolutionary ecologist who never went into the field without half a dozen cans of high‐end smoked oysters and two hip flaks, which didn’t contain water. And so, when I was told by someone in the know of how the most famous geneticist on campus wrote that monumental Nature paper (the one I’d read ten times!) while locked in his office for twelve hours with a six‐pack, I bought into the romance hook, line and sinker. The result: I’ve been nursing a recurring headache for nearly two decades and I’m still waiting on that Nature paper. Most importantly, I now realize the various dangers of romanticizing the bottle, especially for individuals in mentorship positions.Like my idols before me, I’ve accrued a cask full of well‐oaked academic drinking stories, except that they haven’t aged well. There is that heroic evening of intense scotch‐fueled scientific discussion, which led to me forfeiting two front teeth to the concrete sidewalk (my mother still thinks it was a squash accident). Or that time I commemorated the end of a great conference in Barcelona by throwing up on the front window of a café while the most prominent minds in my field sipped aperitifs inside (thank god this was before Twitter). Even more romantic: me buying a bottle of Cotes de Nuits Burgundy at Calgary airport on route to a job interview, discreetly opening the bottle in‐flight because economy class wine sucks, and then being met by airport security upon landing. Let’s just say I didn’t get the job. To some, these anecdotes might seem light‐hearted or silly, but they are actually rather sad and underscore the seriousness of substance abuse. Many readers will have their own complicated experiences with alcohol in academia and, I believe, will agree that it is high time we asked ourselves: are we training our graduate students to be great thinkers or great drinkers? Moreover, this question does not address the equally if not more serious issue of excessive drinking among undergraduate students.As I sit at my desk writing this, I think to myself: is it normal that within a two‐minute walk of my university office there are three different places on campus that I can have a beer before lunch, not including the minifridge behind my desk? Is it normal that in my department the first thing we do after a student defends their thesis is go to the grad club where they can have any alcoholic drink of their choosing for free from the goblet of knowledge, which is kept on a pedestal behind the bar? Is it normal that before the COVID pandemic when I was visiting a prominent university for an invited talk, one of the professors I met with offered me a glass of expensive Japanese gin at 11 am in the morning? (And, yes, I accepted the drink.)Of course, if you don’t want to drink you can just say no. But we are learning more and more how institutional cultures – “the deeply embedded patterns of organisational behaviour and the shared values, assumptions, beliefs or ideologies that members have about their organisation or its work” (Peterson & Spencer, 1991) – can have powerful effects on behaviour. Excessive alcohol consumption is undeniably an aspect of collegial culture, one that is having major impacts on the health and behaviour of students and staff, and one that I’ve been an active participant in for far too long. I’ll be turning forty in a few months and I have to face the fact that I’ve already drunk enough alcohol for two lifetimes, and not one drop of it has made me a better scientist, teacher or mentor. The question remains: how much more juice can I squeeze into this forty‐year‐old pickled lemon? Well, cheers to that.     

Finding autophagy: It’s a question of how you look at it

To tell the truth, I find it difficult to work when flying, or even when sitting in an airport for an extended period of time. So, typically I take along a book to read. And when I truly cannot concentrate, for example when a flight is considerably delayed, I have even been known to resort to word puzzles. Depending on the type, they do not require much attention (that is, you can pick up right where you left off after you glance at the flight status screen for the twentieth or so time, even though you know nothing has changed), or effort (although you need to use a pen or pencil, not a keyboard), but nonetheless they can keep your mind somewhat occupied. I even rationalize doing them based on the assumption that they are sharpening my observational/pattern-finding skills. One type of word puzzle that is particularly mindless, but for that very reason I still enjoy in the above circumstances, is a word search; you are given a grid with letters and/or numbers, and a list of “hidden” terms, and you circle them within the grid, crossing them off the list as you go along. I do admit that the categories of terms used in the typical word searches can become rather mundane (breeds of dog, types of food, words that are followed by “stone,” words associated with a famous movie star, words from a particular television show, etc.). Therefore, on one of my last seminar trips I decided to generate my own word search, using the category of autophagy.     

Elda Grabocka: Stress-buffering comes in granules

Elda Grabocka investigates the role of stress granules in obesity and cancer.

When one thinks of high school, sharing hallways with students from 80 different countries is not the usual image that springs to mind. This was indeed Elda Grabocka’s experience. She grew up in Pogradec, a remote town in Albania—her parents, both physicians, were assigned to this location by the state. Elda won one of the two spots available for Albanian students in a national competition to attend the United World College of the Adriatic in Trieste, Italy, a high school focused on social change that brings together students from around the globe to promote intercultural understanding. Elda still remembers, with a smile on her face, the first glimpse at the laboratories as the senior students were working on their thesis projects: “That was exactly what I wanted to do!” She barely spoke English at the time and had to catch up to the level of her peers, but her perseverance and passion prevailed, and she obtained the International Baccalaureate Diploma (IBD). For the independent study of the IBD program, she submitted a research project in chemistry, which ended up being an important learning and life lesson: “That helped me understand that I was more suited to biology! In hindsight, it was great to have that experience so early; I certainly had no awareness then how essential failing and then learning from your failures is to science, but having a level of comfort with it from the beginning was probably a bonus.”Elda Grabocka. Photo courtesy of Chris Hamilton Photography.But science was not the only professional option Elda contemplated—her volunteering experience with relief organizations in various refugee camps made her consider a career in public health and humanitarian relief efforts. She finally sought a PhD degree in molecular pharmacology and structural biology in the laboratory of Phil Wedegaertner at Thomas Jefferson University. After studying heterotrimeric G-proteins and how the subcellular localization of their exchange factors regulates function, Elda felt the need to seek greener pastures. She went on to do a postdoc on one of longest-studied oncogenes, RAS—her choice wasn’t motivated by the field, but by the mentor, Dafna Bar-Sagi. Elda’s admiration for Dafna is notable when she speaks about her time at the New York University Langone Medical Center: “It’s remarkable how many novel aspects of RAS biology that have shaped and then re-shaped our thinking about this oncogene have come out of her lab; I felt there was a depth and breadth to her approach to scientific research that if I could learn, I’d be able to see more of the angles, so to speak, ask better questions; she has really expanded my mind in all those aspects.” Elda’s work focused on the interplay between the mutated forms of RAS and the wild-type isoforms, which she and others have shown is context dependent, with the wild-type isoforms acting as both tumor suppressors and tumor promoters (1). While still in Dafna’s laboratory, Elda pursued a more independent scientific interest: the role of stress granules in mutant KRAS cells. In 2016, Elda returned to her alma mater, joining the Department of Cancer Biology at the Sidney Kimmel Cancer Center at Jefferson as an assistant professor, with stress granules in cancer as the focus of her laboratory. We contacted her to learn more about her research journey.What interested you about stress granules and their connection with obesity and cancer?I became interested in stress granules and their potential role in cancer early in my postdoc. I read a review by Stephen Elledge’s group where they described the “stress phenotype” of cancer as an important player in tumorigenesis. I realized that cancer cells exist mostly in a state of stress—for example, mutated genes, like oncogenic RAS, are potent inducers of many types of cellular stresses. I was working on a RAS ubiquitination project, and one of the candidates for a RAS de-ubiquitinating enzyme we were looking at was implicated in stress granule formation. Little was known about stress granules at the time—they are induced by types of stresses associated with tumors (hypoxia, oxidative stress, osmotic pressure, proteotoxic stress, metabolic stress, etc.), so the question I asked was whether stress granules could function as a stress coping/adaptation mechanism in cancer. Indeed, I found that stress granules are prevalent in tissues from patients with pancreatic cancer and mouse models of pancreatic cancer. Remarkably, not all cancer cells are the same in their capacity to form stress granules—all cells will make stress granules under stress, but KRAS mutant cancer cells have a heightened ability to do so because signaling from mutant KRAS enhances the levels of a critical molecule to stress granule formation, 15-deoxy-prostaglandin J2 (2). This enhanced capacity to make stress granules, in turn, renders KRAS mutant cells more resistant to stress and more dependent on stress granules; inhibition of stress granules leads to increased cell death in KRAS mutant versus KRAS wild-type cancer cells.Immunofluorescence staining of pancreatic ductal adenocarcinoma tissue showing cancer cells in red, stress granules in green, and nuclei in blue. Image courtesy of the Grabocka laboratory.The work establishing this dependence was in vitro, so the primary goal when I started my laboratory was to determine their relevance in tumorigenesis, which led me to explore their connection to obesity and cancer for several reasons. First, obesity is a major predisposing factor for several cancers, including pancreatic and colon, which are prevalent KRAS-driven cancers for which treatment options are limited. Second, obesity is a complex pathology which likely impacts the pathobiology, the therapy response, and even the evolution of cancers that arise in this setting. Given that cell stress and inflammation are key features in obesity, this would make the ideal background to study the contribution of stress granules in tumorigenesis. I think this pre-existing stress [obesity] might necessitate the engagement of stress adaptive mechanisms from the early stages of tumorigenesis and may also lead to a high dependence on these processes.What are you currently working on, and what is up next for you?It’s a very exciting time to be working on stress granules! The field has grown significantly over the past 10 yr or so, especially with the renewed interest in phase separation. As organelles that form via phase separation when a cell is under stress, stress granules are perhaps one of the best examples of phase separation in vivo and a great platform to understand its relevance. The recent advances in defining the composition, as well as key molecular drivers and their functional domains in stress granule assembly, have been of great benefit. We are now better positioned to define the stress granule–specific functions in health and disease. Because stress granules are induced by various types of stresses, they could function as a pan-stress adaptation mechanism in cancer. This is a very appealing angle, as if we can solve how stress granules enable stress adaptation, which is a major focus of my laboratory, we could have better anti-cancer therapies.The composition of stress granules, comprising hundreds of proteins and mRNAs involved in several aspects of cell biology, prompted me to ask whether cytoprotection under stress is their main and/or only function. What other cellular processes stress granules regulate, whether these vary with the type of stress, and how such processes are integrated into the stress response of cancer cells are burning questions we are currently working on, as the answers will advance our understanding of the role of stress granules in cancer. The “chronic stress” of cancer is heterogenous in both spatial and temporal terms, as well as in the type of stress and intensity. I am also very curious to see if and how heterogeneity in stress stimuli impact the composition of stress granules and the processes they regulate, and how this may affect tumor evolution. Also, cancer cells are not the only cells in the tumor that make stress granules. As a matter of fact, we reported that KRAS mutant cells can stimulate stress granule formation in a paracrine manner. An ongoing project in the laboratory that I’m very excited about is focused on understanding the contribution of stress granules to the pro-tumorigenic microenvironment.What kind of approach do you bring to your work?My approach is very hypothesis and observation driven; the latter in the sense that it can often be that initial spark that inspires an idea, draws connections, and looks for context and meaning. I also find that sometimes the answer to my next question or the question I don’t know to ask yet is hidden right in front of my eyes, so paying careful attention to the data is key. It is also where objective and critical evaluation of experimental results starts. There’s one line that’s firmly ingrained in my mind from my postdoctoral training, which is “Science is self-correcting.” It’s a note of caution that if you don’t pay attention and see only what you want to see, it will still eventually prove you wrong, and you’d have wasted a lot of time in the process. So I try to minimize that waste as much as possible—unavoidable entirely, having a favorite hypothesis is part of the scientific thinking process, but crucial to remember to follow the data and not just convince yourself.What has been the biggest accomplishment in your career so far?I’m still quite early in my career to start listing accomplishments. I feel privileged to do the work I do; I essentially get funded to pursue ideas that I find interesting. So I have a hard time with this question because it has a hint of pride, and when you start adding pride to privilege, as a junior principal investigator especially, it gets a bit too self-serving. I hope that the work we are doing stands the test of time and leads to or helps lead to a meaningful impact on patients’ lives—that would be a great accomplishment.What has been the biggest challenge in your career so far?The past two years of COVID have certainly been a different reality, and a constantly shifting one at that. From a career perspective, so much of a scientific career happens at the bench: experiments happen at the bench, we train at the bench, animal work is long and requires multiple dedicated essential personnel and facilities, so inevitably, remote work, or shift work, limited occupancy, and the shortages we are now seeing in the supply chain have been a major challenge for everyone. I do think junior laboratories like mine experience that a bit harder. The bandwidth to absorb these challenges is much smaller if you’re just starting out, or if you’ve had a laboratory for a couple of years and are just ramping up. I must say though that it has made for stronger teamwork in the laboratory, and we’ve had to be really focused and efficient—so there’s an upside!Out for a paddle. Photo courtesy of Elda Grabocka.Any tips for a successful research career?Hard to say, because certainly it means different things to different people. The only tip I would give perhaps is to define what that means, what that success looks like for oneself, and be true to that. I expect how each one defines it also changes with time and experience, but I do think it’s very important to identify what success means as early as possible and let that be what you measure your efforts against. It’s easy to get distracted, overwhelmed, or even disheartened otherwise. My own definition is quite simple: success is doing what I love to do, working toward answering a meaningful scientific question, and enabling/supporting my trainees to reach their potential—keeping that in mind has been very important and helpful.     

Freelancer

What long‐term changes can we expect, in how academic work is conducted and remunerated, in the post‐pandemic world? Subject Categories: S&S: Economics & Business, S&S: History & Philosophy of Science, S&S: Ethics

Although still two years away, my looming “retirement” from university employment is inevitably going to herald a major change of life. “Of course, you''ll become ‘Emeritus’”, most colleagues have opined. My answer to all of them has been a firm “No. I''ll become a freelancer”. The concept of a freelance scientist is obviously so alien to most of them that they invariably change the subject immediately. However, my gut feeling is that in 20 years or less, almost all of us will be freelancers of some kind.The COVID‐19 pandemic has altered the world of work in very obvious ways. There has been much talk of how the changes are likely to carry over to the future, even if more traditional patterns will probably reassert themselves in the short to medium term. Working from home, conducting meetings remotely, not wasting days travelling between continents for a few precious hours of face‐time and being free to structure workdays around our own priorities: these are the most obvious novelties that many believe will continue long after the effects of the pandemic on health and wealth have faded. But I have a slightly different take.Major disruptive events of worldwide import—world wars, global economic slumps, cataclysmic volcanic eruptions and pandemics—have often been harbingers of profound social change. This is not only due to their direct and immediate effects, but more so because the disruption accelerates and facilitates changes that were already happening. In the case of COVID‐19, one may place in this category the demise of cash, the rise of streaming services in place of live entertainment, online grocery shopping and even virtual dating. Another is paying people to stay home and do nothing, otherwise known as the universal basic income (or, in the USA, “stimulus cheques”).Inefficient practices in academia are equally ripe for change. Why bother with classes for 500 first‐year students when a much better edition of the lecture by an expert communicator is available on the internet? What’s the use of an ageing PhD advisor 20 years away from bench science, who struggles to guide the next generation of experimentalists in the lab, when the expertise of a plethora of specialists can easily be accessed online? What’s the value in published papers that are read by fewer people than wrote them? Or in seminars delivered to a roomful of attentive postdocs and PhD students who lack the courage or the time to address even a single question to the speaker?Yes, there is still great value in small‐group teaching and mentorship, in the creative verve of a close‐knit laboratory team, and in good writing and oratory: but the required skills are already different from those in which we were schooled. Thus, even if I do not hold in my palm the crystal ball to predict exactly which changes will happen and how fast, I believe that our traditional jobs are going to melt away very fast in the post‐pandemic world. Universities and research institutes may still exist, but I expect that their practices will be different, reshaped by rational need more than by tradition. Today’s academic science is already quite unlike that of 1920, but it has evolved so slowly during that century—spanning a much longer time period than the lifetime of a scientific career—that we barely perceive the changes that have occurred. In contrast, the changes now afoot will certainly happen much faster, especially since the funds to support the current “inefficient” model are likely to diminish rapidly.So, I predict that university teaching and science communication in general will be the first to evolve into freelance activities, where universities will invite bids from individuals or their agents and award commissions on a fee‐paying basis rather than using salaried employees. But these are not the only component parts of academia facing such a shake‐up. The practices of laboratory science are also likely to be rebuilt. When discussing with colleagues how research might be undertaken on a freelance basis, they usually raise issues such as bricks and mortar and the complex infrastructure that is needed to sustain cutting‐edge research, especially in the life sciences: how, they ask, could a freelancer access state‐of‐the‐art imaging, mass spectrometry or DNA sequencing? How could their acquisition of such expensive hardware possibly be financed, especially if they had to somehow acquire it personally and set it up in the garage or carry it around with them?But the answers to these questions are already evident in the practices of some major research agencies, most notably in Europe’s pioneering funder of single‐investigator grants for blue‐skies science, the European Research Council (ERC). The ERC already treats its awardees as freelancers, in the sense that it encourages them to shop around for the most attractive venue in which to embed and implement their research project. The quest for the best host institution takes place not only at the preparatory step of an ERC application: it also happens after the grant is awarded, since the grant money is considered inherently portable and can even be moved later on from one institution to another. This encourages potential host universities to compete for providing the best research environment, in which many factors come into play, not just but not least, the quality of its research infrastructure. How well it supports, rather than burdens its staff with administrative tasks, the nature of its recruitment and personnel policies, how it handles relocation issues for incoming researchers and their families, what opportunities it provides for further training in relevant skills and career development: these are just some of the factors in play.In recent years, universities have seen their primary role in this process as encouraging their own tenured or tenure‐track staff to apply for ERC grants. But I foresee the emphasis shifting increasingly to investigators who seek out universities that can make the most appealing offer, whilst universities and government agencies standing behind them will shape their policies so as to remain competitive. Moreover, in such a landscape there is no reason why a scientist cannot operate research projects on multiple sites if this offers the most convenient arrangement. The tools for remote meetings and cloud computing to which we have all become accustomed mean that there is no longer any need for a research group to be located in one building or even in one country, to operate efficiently as a team.At the same time, many of the tasks involved in running a research institute or department can be efficiently outsourced to the most competitive bidder—to be assessed on the basis of value‐for‐money, not just minimum cost. As a society, we should be asking ourselves why we continue to waste the talents of highly specialized scientists on performing admin tasks for which they are neither properly trained nor motivated, instead of just engaging a smart‐software developer. Why should we fund creative thinkers to undertake laboratory projects in host institutions that do not have the required state‐of‐the‐art facilities to perform them? Or allocate budgets that are so pared down that grantholders cannot even afford to purchase such services elsewhere? Why should we expect them to make do with poorly paid trainees instead of a team of professionals? And why should we continue to organize research in pyramid structures where everything depends on commands from the top, where all findings are announced using an institutional slide template, where colleagues elsewhere are considered as untrustworthy “competitors”, and where credit for individual creativity is usurped by seniors who barely know the contents of the papers they “write”?In the “old system”, we have all gotten used to making do with sub‐optimal working arrangements and grumbling about them, whilst considering them an immutable fact of life. But I envisage a time coming soon where we scientists will have the edge in reshaping the market for teaching and research in a way that is much more to our liking and properly aligned with our skills. At the same time, our individual success in accomplishing our professional goals will have a direct effect on our income and job satisfaction, and steer us towards activities where our talents are most effectively deployed. In short, I believe that we, as freelance scientists, will be much more firmly in control of science in the future and that time is not far off.     

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.