A career pathway in protein folding: from model peptides to postreductionist protein science

This review discusses the inherent challenge of linking "reductionist" approaches to decipher the information encoded in protein sequences with burgeoning efforts to explore protein folding in native environments-"postreductionist" approaches. Because the invitation to write this article came as a result of my selection to receive the 2010 Dorothy Hodgkin Award of the Protein Society, I use examples from my own work to illustrate the evolution from the reductionist to the postreductionist perspective. I am incredibly honored to receive the Hodgkin Award, but I want to emphasize that it is the combined effort, creativity, and talent of many students, postdoctoral fellows, and collaborators over several years that has led to any accomplishments on which this selection is based. Moreover, I do not claim to have unique insight into the topics discussed here; but this writing opportunity allows me to illustrate some threads in the evolution of protein folding research with my own experiences and to point out to those embarking on careers how the twists and turns in anyone's scientific path are influenced and enriched by the scientific context of our research. The path my own career has taken thus far has been shaped by the timing of discoveries in the field of protein science; together with our contemporaries, we become part of a knowledge evolution. In my own case, this has been an epoch of great discovery in protein folding and I feel very fortunate to have participated in it.     

Building a science in Japan: The formative decades of Molecular Biology

I am honored to have been invited to participate in this Workshop on Comparative Studies of Building Molecular Biology, with a discussion of Japanese experiences in constructing a science — in this case, the discipline of molecular biology. As I understand it, the construction of a science must be equivalent to building a new culture. My having given this title to my paper suggests that I have enough knowledge about the subject to perhaps even extrapolate its course into the future — which I do not. What I do have is a sincere admiration of my old friends and colleagues, in Japan and elsewhere, who together tried to build a new science of molecular biology in Japan.     

IV.–Field-notes on the Birds of Sierra Leone.

T he following notes were mostly made during twelve months' service in Sierra Leone, West Africa, 1921-22, of which nine and a half months were passed at Freetown and two and a half in the hinterland. During this latter period I had, however, not much time for observation, as I was travelling daily. My route was a circular one, from Freetown to Port Lokko by canoe, thence to Mabanta, and eastward from there to about the centre of the Panguma District; northward to Falaba, thence westward and southward through the Kariua District back to Port Lokko. Although all my collecting was done, and most of my notes made during the twelve months above referred to, I had had two previous tours of service in this country, and observations made then have helped to confirm some of my conclusions. Ornithology was the recreation of my spare time, which was of course limited.     

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.”     

II.—Notes on Some Birds in Egypt

As a lover of birds who has noted regularly for over twenty-five years all he saw in Egypt I have been most interested to read Col. Meinertzhagen's 'Nicoll's Birds of Egypt' (1930). The following notes in most cases amplify those of Meinertzhagen; in others they show where my observations do not appear to have coincided with his.     

Wallace P. Rowe lecture. Poxviruses of laboratory animals

Currently the subfamily Chordopoxvirinae, the poxviruses of vertebrates, is subdivided into eight genera, containing some 20-30 species; an inexact figure because the birdpox viruses have not yet been properly investigated taxonomically. I have discussed seven species belonging to three genera, all of which have caused infection and usually disease in mammals commonly used in the laboratory. The list could have been extended had I included chickens and swine as laboratory animals, for that would have meant that I would have spoken about the birdpox viruses and swinepox virus as well. However, I think I have said enough to remind you of the importance of this family of viruses to those of you concerned with laboratory animal medicine. I believe that Wally Rowe would have been interested, for every case I have described presents problems in the ecology of viruses, and like my mentor Macfarlane Burnet, Wally approached virology from an ecological point of view, whether he was thinking about the DNA provirus of retroviruses and the host chromosome, the pathogenesis of disease, or the spread of viruses in animal populations, all topics to which he made major contributions.     

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.     

You are the most valuable reagent in the lab: mental health before and during the pandemic

No one maps out their tenure as a postdoc anticipating a life-altering tragedy. But mental health crises of all kinds affect academic trainees and staff at similar or higher levels than the general public. While the mental health resources available to trainees are often set by healthcare providers, all levels of university leadership can work to remove material and immaterial obstacles that render such resources out of reach. I describe how access to care via telemedicine helped me following a loss in my family.

Over the years, my siblings and close friends have sought mental health resources like therapy, psychoanalysis, or psychiatry, so I loosely understood their benefits. When I was a PhD student I went to therapy briefly, but my counselor and I decided I could do without it. Since I started my postdoc, stress manifested in some new ways but I managed it well with my usual coping strategies and support. That changed one bright December morning in 2019 while I was preparing for our weekly lab meeting. My phone rang indicating a call from my father, whom I had spoken to the night before to celebrate the news of my nephew’s birth. But the voice on the phone was that of a family friend, telling me that my father had died overnight of an undiagnosed heart condition. In the moment I couldn’t even understand what was happening, saying over and over, “but I talked to him last night.” Soon I was sitting at home, dazed, on a string of tearful calls with family and friends.I often read words like “lifted” or “buoyed” to describe the stabilizing support of a network of loved ones. In my case this network was tethering me to reality over the next few weeks, preventing me from spinning off the Earth’s surface in a storm of sorrow and anxiety. The trauma also took a strange physical form and convinced me that I was suffering from a cardiac condition of my own. I had a panic attack during which I went to urgent care convinced my own heart was about to give way. Night after night these physical symptoms prevented me from sleeping.Graced by many loving connections with my siblings, my boyfriend, and close friends, I was actually weathering the process as well as one can. My PI gave me a firm directive to take as much time off as I needed. These were two key elements early in my healing process: a supportive network and an understanding advisor. The third was getting professional help, which I soon realized I needed. Even if I felt OK one day, I didn’t trust that I’d be OK the next. My grief formed too thick and too broad a landscape for me to navigate without help.Deciding to seek mental health resources and realizing that one needs them are often the hardest parts. Connecting with those resources once the decision has been made should be as simple as possible. I called a mental health number, and a triage counselor noted my therapy needs and verified my insurance. She asked what times and locations I preferred and then searched for an open appointment with a therapist who accepted my insurance. She also informed me that my coverage allowed 12 sessions with no copay, which was a pleasant surprise. The therapist who agreed to see me had very few openings, in part because this all happened in December—the holidays are especially busy for therapists. I was aiming for a time after normal working hours, or in the morning before I would head to lab, but none of those times were available. I didn’t like interrupting my workday to trot off to therapy. Taking a long break once a week meant I couldn’t run experiments or mentor my student during that time. But I made the sacrifice because my highest priority was getting the help I needed. There was no shortcut. Prioritizing mental health over lab work is tough for researchers, and I would never have accepted that kind of weekly disruption before my dad’s passing. But as a wonderful mentor of mine used to say, “You are the most valuable reagent in the lab.” She wasn’t describing mental health at the time, but the phrase now provided a guiding principle for my recovery. My first few sessions were on Tuesdays at 2:00 pm.The afternoon break turned out to be less disruptive than I had feared, because I had recently come back to the lab and was working short days. Had she asked, I would have told my PI where I was on Tuesday afternoons, but she wasn’t normally abreast of my daily schedule, so I didn’t seek her approval beforehand. Coordinating experiments with lab members thankfully wasn’t an issue because my work was largely independent; I simply let lab members know that I’d would be out of the lab for a bit on those days.The weeks went by, and the benefits of therapy accrued, helping me in large and small ways as I grieved. In mid-March of 2020, my therapist followed public health guidelines and asked all her clients to transition to remote sessions. While this was easy and sensible, it was still a little disappointing. Therapists are professional empaths, among many other things, and doing away with the physical presence and exchange with her was a blow. Yet therapy via video felt less odd simply because most of my social interactions were now virtual. Thankfully I didn’t have to move out of state for the lockdown (as did many students living in campus housing), which meant I could stay with the same therapist without any insurance complications.A few weeks into lockdown, I asked my therapist whether we had reached the limit of my 12 sessions without a copay. She replied with the good news that my insurance provider had waived all copays for mental health costs due to the pandemic. By that time therapy had generated a platform and an outlet to explore areas of my grief beyond the trauma of my father’s passing. Without needing to weigh the costs and benefits of this resource, I saw my therapist for another 4 months. I slowly took stock of my upbringing in an unconventional family and the loss of my mother when I was 25 and waded through a series of difficult decisions regarding my father’s estate. My father’s death changed me at a depth that is untouched by any amount of therapy or treatment. I’m not “healed”: I feel aged, more brittle, and a little ground down compared with who I had been. But therapy guided me through the worst of my grief, past the acute trauma to help me grasp what I was going through.Since the pandemic began, the number of people reporting increased stress or mental health issues has steadily increased (information on the impact of COVID-19 measures on mental health: https://www.apa.org/workforce/publications/depression-anxiety-coronavirus.pdf) (also see Mental health resources for trainees). I am fortunate to have affordable health insurance and the support from my lab and my department. The ease of finding my institution’s phone number for mental health resources was itself an important benefit. I share these pieces of my story with humility and understanding that not everyone enjoys the privileges that I do and the knowledge that everyone weathers life’s tragedies in their own way. It is not lost on me that some benefits stemmed from a policy change made by a private insurance provider. The provider made the right decision to waive copays, freeing me from having to choose between cost and my mental health needs. Yet had I been a student who had to move out of state due to COVID-19, access to mental health resources might have been disrupted or cut off. The need for reduced out-of-pocket costs for healthcare is known and needs no repetition, but the benefits of telehealth should be a low-cost component of health plans offered to students and staff (information on telehealth recommendations: https://www.apaservices.org/advocacy/news/congress-patient-telehealth?_ga=2.231013471.1538013741.1619359426-1228006513.1619359425 and http://www.apaservices.org/practice/advocacy/state/leadership/telebehavioral-health-policies.pdf?_ga=2.3385904.1067518037.1620039082-1228006513.1619359425.I’m not a cloud of emotions attached to a pair of good pipetting hands, I’m a human who is choosing to spend my time doing research. This observation is easy to repeat, by trainees as much as by faculty and administrators, but much harder to act upon in the midst of conflicting priorities. Consider my story a success: Because I could access the resources I needed, I was able to prioritize my mental health in the midst of my ambitious research program even during the lockdown.MEET THE AUTHORI have been a postdoc in Stefani Spranger’s lab at MIT for 4 years. Supported by an Irvington Fellowship from the Cancer Research Institute, my work examines the behaviors of dendritic cells in tumors that contribute to productive or unproductive anti-tumor immune responses. My doctoral work examined modes of multicellular invasion controlled by the actin cytoskeleton with Margaret Gardel at the University of Chicago. Earlier I was a lab technician with Thea Tlsty at the University of California, San Francisco, which followed a bachelor’s degree in biology at the University of California, Santa Cruz. I serve on the Committee for Students and Postdocs at the American Society for Cell Biology, where I chair the Outreach Subcommittee.     

My Journey to DNA Repair

I completed my medical studies at the Karolinska Institute in Stockholm but have always been devoted to basic research. My longstanding interest is to understand fundamental DNA repair mechanisms in the fields of cancer therapy, inherited human genetic disorders and ancient DNA. I initially measured DNA decay, including rates of base loss and cytosine deamination. I have discovered several important DNA repair proteins and determined their mechanisms of action. The discovery of uracil-DNA glycosylase defined a new category of repair enzymes with each specialized for different types of DNA damage. The base excision repair pathway was first reconstituted with human proteins in my group. Cell-free analysis for mammalian nucleotide excision repair of DNA was also developed in my laboratory. I found multiple distinct DNA ligases in mammalian cells, and led the first genetic and biochemical work on DNA ligases Ⅰ, and Ⅳ. I discovered the mammalian exonucleases DNase Ⅲ (TREX1) and IV (FEN1). Interestingly, expression of TREX1 was altered in some human autoimmune diseases. I also showed that the mutagenic DNA adduct O6-methylguanine (O6 mG) is repaired without removing the guanine from DNA, identifying a surprising mechanism by which the methyl group is transferred to a residue in the repair protein itself. A further novel process of DNA repair discovered by my research group is the action of AlkB as an iron-dependent enzyme carrying out oxidative demethylation.     

Scheel D. and Wasternack C.(eds) Plant Signal Transduction.

The recent whole-scale sequencing of several organisms has revealedtwo surprising facts to me. Firstly, I as a human with considerablepride in the genetic complexity controlling my differentiation,my immune response, my memory and my behaviour, really do nothave so many more genes compared to plants. Secondly, when surveyingthe genomes of mammals, flies and worms, I found about 50 receptorkinase genes per genome, whereas plants possess about 400. Whatare all the receptors doing in     

Biomechanical modeling and sensitivity analysis of bipedal running ability. II. Extinct taxa

Using an inverse dynamics biomechanical analysis that was previously validated for extant bipeds, I calculated the minimum amount of actively contracting hindlimb extensor muscle that would have been needed for rapid bipedal running in several extinct dinosaur taxa. I analyzed models of nine theropod dinosaurs (including birds) covering over five orders of magnitude in size. My results uphold previous findings that large theropods such as Tyrannosaurus could not run very quickly, whereas smaller theropods (including some extinct birds) were adept runners. Furthermore, my results strengthen the contention that many nonavian theropods, especially larger individuals, used fairly upright limb orientations, which would have reduced required muscular force, and hence muscle mass. Additional sensitivity analysis of muscle fascicle lengths, moment arms, and limb orientation supports these conclusions and points out directions for future research on the musculoskeletal limits on running ability. Although ankle extensor muscle support is shown to have been important for all taxa, the ability of hip extensor muscles to support the body appears to be a crucial limit for running capacity in larger taxa. I discuss what speeds were possible for different theropod dinosaurs, and how running ability evolved in an inverse relationship to body size in archosaurs.     

"Craziness" and "visions": experiences after a stroke.

For a stroke victim there may be at least three types of strange occurrences: incorrect saying, seeing, and thinking. To the patient only the third seems to be "crazy". After a stroke (left hemisphere), which mainly produced serious aphasia, I (the patient) felt crazy two or three times when someone said something I expected him to say. On the other hand, my initial aphasic "gibberish speech" and an occasional false vision did not seem crazy. In my case the vision is always a car or a child, seen on my extreme right, where I am otherwise blind from the stroke. I am always driving when it happens; in recent years this phenomenon occurs when I am tired or tense, or the light is poor. These rapid visions do not seem insane but merely physical problems in my eyes, much like ordinary people''s dreams.     

Sampling phylogenetic tree space with the generalized Gibbs sampler

A recent article published in Cladistics is critical of a number of heuristic methods for phylogenetic inference based on parsimony scores. One of my papers is among those criticized, and I would appreciate the opportunity to make a public response. The specific criticism is that I have re‐invented an algorithm for economizing parsimony calculations on trees that differ by a subtree pruning and regrafting (SPR) rearrangement. This criticism is justified, and I apologize for incorrectly claiming originality for my presentation of this algorithm. However, I would like to clarify the intent of my paper, if I can do so without detracting from the sincerity of my apology. My paper is not about that algorithm, nor even primarily about parsimony. Rather, it is about a novel strategy for Markov chain Monte Carlo (MCMC) sampling in a state space consisting of trees. The sampler involves drawing from conditional distributions over sets of trees: a Gibbs‐like strategy that had not previously been used to sample tree‐space. I would like to see this technique incorporated into MCMC samplers for phylogenetics, as it may have advantages over commonly used Metropolis‐like strategies. I have recently used it to sample phylogenies of a biological invasion, and I am finding many applications for it in agent‐based Bayesian ecological modelling. It is thus my contention that my 2005 paper retains substantial value.     

The story of science: successes,failures, luck,privilege, and bias

I am incredibly honored to receive the 2021 WICB Junior Award for Excellence in Research in WICB’s golden jubilee year. In this essay, I traverse my scientific journey starting with my PhD, highlighting the highs and the lows and how these intersect with luck, privilege, and bias.

V. AnanthanarayananMy pursuit for a PhD started with a hiccup—I had applied to several places in the United States, but barely got any offers due to the economic upheaval that happened that year (2008). I had to forgo any dreams of a PhD in the United States and remained in Bangalore, India to complete a project I had started with William (Bill) Thies at Microsoft Research India on a programming language for expressing biology protocols. Applying to U.S. schools was an expensive task, one which I was unwilling to put my family through again. So, a year later, when I recommenced my search for a PhD position, I set my sights on Europe. I had heard about the PhD program at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG ) at Dresden from a friend who had just joined the institute for her PhD. Fortunately, I received an interview call from MPI-CBG. At the end of a crucial interview week at Dresden, I “matched” with Iva Tolic´’s (now Institut Ruđer Boškovic´, Croatia) lab for my PhD. At the start of my PhD, I knew next to nothing about the cytoskeleton, motor proteins, or microscopy, but I found Iva and my lab members to be some of the warmest and most welcoming people. I made friends for life and graduated with a PhD in Biophysics, with a thesis focused on understanding the regulation of the motor protein cytoplasmic dynein. I was lucky to have been able to get a position at MPI-CBG and join Iva’s lab—of the other three places in Europe I had applied to for a PhD, only one other institute invited me for an interview, which also proved to be unsuccessful.On completing my PhD in 2014, I didn’t quite know what I wanted to do. Due to personal reasons, I had to return to India and was open to options in both industry and academia. But with my training in motor protein and cytoskeleton research, I had some ideas for exploring scientific questions related to dynein activation. However, most labs I approached for a postdoctoral position were not open to a project that was outside the realm of their research focus. Nonetheless, Iva, Nenad Pavin (University of Zagreb), and Jonathon (Joe) Howard (Yale University), who were members of my thesis advisory committee, gave me the courage to continue in academia. In my naïveté, I went ahead and applied for the INSPIRE Faculty Fellowship, which is targeted at fresh PhDs and junior postdoctoral fellows to establish their own independent group at an Indian institute. To my surprise, I ended up getting the fellowship. The next issue was finding a host institute that was preferably in Bangalore, where my partner was based. I applied at a few different places, but only after I attended IndiaBioscience’s Young Investigator Meeting in 2014 did I get the chance to meet representatives of potential host institutes, including the Indian Institute of Science (IISc). After a couple of research seminars at IISc, my application was assessed and I was offered the position of INSPIRE Faculty Fellow at the newly formed Centre for BioSystems Science and Engineering, IISc.While I did not have any additional start-up funding, I was given the infrastructure and the independence to pursue my research program. It was slow and frustrating at the start, not unlike most starting labs. I always wondered if it might have been easier if I had had a regular postdoctoral stint. During this time, I also started recognizing how hard it was to be a woman in Indian academia. As a woman principal investigator, one’s authority, expertise, and ability are constantly called into question. Justifying your presence in academia on a daily basis is an exhausting task. I had a great mentor in Sandhya Visweswariah (IISc) who helped me navigate the system. I also had an extremely supportive partner, who kept me going through some of the worst times. Eventually, my lab and I landed on our feet (more about this in “My INSPIRE’d Journey”). Our research has been recognized with grants and awards, but one of the most rewarding parts of the job is seeing other lab members discovering the joy of science (I wrote about my approach to mentorship recently [https://www.nature.com/articles/s41580-020-0256-6]).Three years into the faculty fellowship, I was able to transition to an Assistant Professor position in the same institute. However, this did not change my experience as a young woman in Indian science, and the implicit and explicit biases continued. In 2020, I accepted a fantastic opportunity to further my lab’s science as an EMBL Australia Group Leader at the Single Molecule Science Node at UNSW Sydney and made the move during a pandemic. My lab’s research focus is in understanding how stochastic and rare events pertaining to cytoskeleton and motor proteins give rise to complexity in intracellular organization. With this theme as the essence of our research, we ask specific questions about motor protein regulation to effect differential cellular trafficking, mitochondria-microtubule interactions, and their role in mitochondrial dynamics, and we aim to determine barcodes of global organelle positioning in health and disease.I have the privilege of being able-bodied, born in an upper middle-class family to college-educated parents who were extremely supportive of my choices. I have also inordinately benefitted from the fact that I was born to an Indian ‘upper caste’ family. I therefore had an undue head start in life. These were circumstances beyond my control and yet played a huge role in how my story turned out. I was embarrassingly ignorant of the rampant misogyny in academia until I had to contend with explicit and implicit gender-based biases myself when I started my independent research group in India. Women make up ∼40% of science PhDs awarded in India but represent only ∼13% of Indian academia (biaswatchindia.com), highlighting the stark gender biases at play in creating a leaky pipeline. While I tried my best to voice my discontent and affect changes to create an equitable environment within my department and institute, it was slow work. In 2020, when the pandemic hit and all conferences and meetings went virtual, conference posters advertised on social media made it immediately apparent just how much women were underrepresented in Indian STEM conferences. So, I teamed up with Shruti Muralidhar (now a scientist at Deep Genomics, Canada) to found BiasWatchIndia, an initiative to document women representation and combat gender-biased panels in Indian STEM conferences.BiasWatchIndia has been in existence for a little over a year now—we have achieved several milestones, but there’s still so much to do. “Manels” (conferences that feature only men) are still as rampant as they were when we first started—40% of all Indian STEM conferences are manels. And while we have just about started to tackle the underrepresentation of women in Indian STEM, we are conscious of the intersectionality of bias with gender, caste, ableism, and socioeconomic background and aim to understand how best we can advocate for all minorities.People who are in power in academia and who oppose equity, diversity, and inclusion initiatives and instead preach merit and equality as the gold standard need to introspect, because when options and opportunities are offered without consideration to the millennia of oppression based on gender, race, and background, it is not promoting equality but upholding values that will continue to oppress underrepresented groups. Still, I am optimistic and hope to see real changes that will result in equity in academia in my lifetime.     

Problems in the Psychology of Activity

My purpose today is to sum up a number of the postulates concerning activity as it is used in psychology, without introducing any new ones; and I shall do this with the following in mind. Until now I have used a system of concepts I proposed earlier with respect to an analysis of activity; of course, I should like to work out a position, first and foremost my own, on this system, and to reexamine it. On the other hand, I should like to pose a number of questions, such as: Is this system of concepts of any significance, i.e., is it able to work in psychology? Obviously, this system must be developed, which essentially has not been done in recent years. This system of concepts is frozen, without any movement. I personally was quite alone in this respect. All movement takes place with regard to various problems contiguous with the problem of activity, some more, some less; but in my opinion, the concept of activity has been developed highly unsatisfactorily. That is why I thought I should try, today, to sum up very briefly what I think is important.     

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.     

Teaming up: from motors to people

When I reflect on how I became a cell biologist and why I love being one today, one thing that comes to mind is the many terrific collaborations I have had. The science I am most proud of from my graduate and postdoctoral training would not have been possible without working in teams with other scientists. Now, in my own group, much of our best work is being done collaboratively, both within the lab and with other labs. In this essay, I will highlight my experiences working in teams as a trainee, the role teamwork has played in my own research group, and how important I think collaborative science is for the future of biological research.