Ye Tian: Surveilling stress to live longer

Ye Tian investigates how mitochondrial stress signaling pathways regulate longevity using C. elegans as a model system.

An avid reader, Ye Tian used to save up her child allowance with the sole purpose of buying science fiction books. Reading and solving mathematical problems were her favorite hobbies; indeed, she liked mathematics so much that she was about to enroll herself as an architecture major but finally chose biotechnology. Ye moved from her hometown in the Northwest of China, Baoji—famous for housing the Zhou dynasty’s bronzeware and being close to the Terracotta Army—to Beijing for her college and graduate studies.Ye is proud of being among the earliest researchers working on Caenorhabditis elegans in her country; for her PhD studies, she joined the lab of Hong Zhang, who at that time has just established the first C. elegans lab in China at the National Institute of Biological Sciences in Beijing. Ye identified epg-2 as an adaptor for cargo recognition during autophagy. In 2010, she crossed the Pacific toward the U.S. West Coast for her postdoctoral training in the aging field with Andrew Dillin, first at the Salk Institute in San Diego and then at the University of California, Berkeley. There, she discovered that mild mitochondrial stress during development in worms rewires their chromatin landscape to establish specific gene expression patterns throughout the lifespan and promote longevity.Ye Tian. Photo courtesy of Ye Tian.Ye came back to China at the end of 2016 to start her own lab at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences. Her research team studies mitochondrial stress signaling pathways and their interplay with aging. We chatted with her to learn more about her next scientific plans.What interested you about the interplay between mitochondria and aging?I became interested in mitochondrial biology during my postdoc in Andrew Dillin’s lab. Since the origin of eukaryotic cells, mitochondria have been a driving force of evolution. During reproduction, mitochondria are passed from the mother to the offspring through egg cells and they exhibit a unique inheritance pattern. As essential hubs that dictate cellular metabolism, it is clear now that mitochondria and the nucleus maintain a bidirectional communication. Early life “stressed” mitochondria communicate with the nucleus to induce gene expression changes that are beneficial on longevity and persist throughout the lifespan. The fact that mitochondrial function is crucial to aging fascinated me; I wanted to continue exploring that topic further, and that’s why I established my lab around the question of how mitochondrial surveillance mechanisms regulate the aging process.What are you currently working on? What is up next for you?My research team focuses on the interplay between mitochondrial stress signaling pathways and aging. The first work that my lab published was a project that I started during my postdoc. The Dillin lab reported a phenomenon in which perturbations of mitochondria in neurons induced a mitochondrial stress response in the peripheral tissues and hypothesized that a secreted signal molecule, named after mitokine, is required for the cell non-autonomous regulation (1). The identity of this molecular signal remained elusive for almost ten years until we found that a secreted Wnt ligand, EGL-20, functions as the mitokine to coordinate mitochondrial stress signaling across tissues and promote longevity of the organism (2). We are also interested in how the crosstalk between mitochondria and the nucleus influences lifespan. We found that mitochondrial perturbations alter the nuclear epigenome to induce longevity via the histone deacetylation complex NuRD in response to cellular acetyl-CoA levels, the key metabolite at the entry point of the Krebs cycle (3).Lab group picture; current lab members (2021). Photo courtesy of Ye Tian.Our latest work stemmed from a serendipitous observation that neuronal mitochondrial stress is sensed by and transmitted through the mitochondria in the germline. Intergenerational, maternal inheritance of elevated levels of mitochondrial DNA via the mitokine Wnt/EGL-20, which causes the activation of the mitochondrial unfolded protein response (UPR^mt), provides descendants with a greater tolerance to environmental stress. This makes the offspring live longer (4).Among our short-term scientific plans, we’re determining how mitochondria functions during the aging process at both the genetic and biochemical levels and searching for ways to apply our findings from C. elegans to neurodegenerative disease models in mammals.What kind of approach do you bring to your work?The curiosity about how things work drives me; what I enjoy the most is when I see things happening in front of my eyes and when I figure out why they occur that way. That enthusiasm is what I try to spread to my team every day. In the lab, we rely on C. elegans as our model system and on genetics to dissect complex biological processes like aging. We have also adapted modern biochemical and imaging techniques as well as bioinformatics to complement our genetic studies. I’m a geneticist at heart, and I like to initiate a project with a well-designed genetic screen. The best part is that the screen often leads me to answers I was not expecting, and that’s genuinely inspiring!What did you learn during your PhD and postdoc that helped prepare you for being a group leader? What were you unprepared for?Like most scientists, my research career has gone through ups and downs. I had to change my research project in the last year of my graduate school; that was nerve-racking, but I eventually managed to redirect my thesis and get exciting results under time pressure, thanks in large to the support of my parents, mentors, and lab mates. That helped me prepare to become a principal investigator; I gained confidence in problem solving, and since I’ve experienced the stress of dealing with last-minute scope changes firsthand, I connect better with my students.I guess, as many other non-native English speakers, I wasn’t prepared for writing grants and papers fluently in English. This issue wasn’t obvious during my graduate and postdoctoral studies, as my mentors were always there for me and proofread and edited my writing. Now I have to stand up for myself. I spend most of my time writing; I’ve improved my writing skills but it’s still an ongoing process.Reconstruction of the nerve system of C. elegans by confocal microscopy. Green corresponds to YFP-labeled neuronal specific marker Q40, and red labels germline specific mitochondrial outer membrane protein TOMM-20::mkate2. Image courtesy of Ye Tian’s lab.What has been the biggest accomplishment in your career so far?My very first PhD student, Qian Zhang, graduated with two first-author papers and decided to pursue a research career in academia. Being responsible for someone else’s career is challenging but also rewarding.What has been the biggest challenge in your career so far?I use the model organism C. elegans for my research in aging, so from time to time, peers criticize the relevance of my work to human health. I’m used to justifying my scientific approach to funding agencies and peers in other fields, but sometimes it’s exhausting or not pleasant.Who were your key influences early in your career?My PhD mentor, Hong Zhang. He is very passionate about the science he does, and he is courageous to shift his research directions to answer new biological questions.What is the best advice you have been given?I think the best advice I’ve gotten is that “tomorrow is another day.” It reminds me to keep going and be optimistic.What hobbies do you have?I love art and music. When I was in San Diego, I used to play in the Chinese Music Band; I miss my musician friends over there. In my teens, I used to hike mountainside trails along the river with my parents. Now, running has become my new favorite hobby. I enjoy the tranquility and peace of mind while running; it’s soothing.     

The case of philanthropy: bringing scientists and philanthropic donors together,for good

Summary: Philanthropists and scientists share many common interests, and yet they are not familiar with each other''s ways of thinking. This Editorial highlights how to improve their mutual understanding to advance research and life sciences.

“Wealth is not new. Neither is charity. But the idea of using private wealth imaginatively, constructively, and systematically to attack the fundamental problems of mankind is new.” – John Gardner

Philanthropy, derived from private wealth, stands unique as a vital source of scientific funding. Yet many scientists don''t truly understand the workings of this form of charitable giving. Some are even wary of it, and believe that a divide between the worlds of science and business is a normal state of affairs. My experience has exposed striking similarities between the two specialties: both dedicate their resources to innovation and the sincere desire to do good for their fellow man.I''ve been lucky to work on both sides of the fence. I conducted research for my PhD at the Wistar Institute in Philadelphia, PA, and at Sloan Kettering Institute in New York City, NY, where I worked on the Id1 gene and its role in the molecular mechanism of mammalian cell differentiation. I later moved to the Pershing Square Foundation. In 2013, to support young investigators with bold and risky ideas in cancer research in the New York area, the Pershing Square Foundation partnered with the Sohn Conference Foundation to create the Pershing Square Sohn Research Alliance (PSSCRA). Since the organization''s founding, I have served as its Executive Director. As a result of my career experience, I understand firsthand the role of philanthropic support of medical research. I am always excited to work with new, young and innovative talent, and to introduce that talent into the social mainstream.     

Gaia Pigino: Inside the cell

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

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

A sustained passion for intracellular trafficking

I am honored to be the first recipient of the Women in Cell Biology Sustained Excellence in Research Award. Since my graduate school days, I have enjoyed being part of a stimulating scientific community the American Society for Cell Biology embodies. Having found myself largely by accident in a career that I find deeply enjoyable and fulfilling, I hope here to convey a sense that one need not have a “grand plan” to have a successful life in science. Simply following one''s interests and passions can sustain a career, even though it may involve some migration.     

Twists and Turns: My Career Path and Concerns About the Future

THE Genetics Society of America’s Thomas Hunt Morgan Medal is awarded to an individual GSA member for lifetime achievement in the field of genetics. The 2014 recipient is Frederick Ausubel, whose 40-year career has centered on host–microbe interactions and host innate immunity. He is widely recognized as a key scientist responsible for establishing the modern postrecombinant DNA field of host–microbe interactions using simple nonvertebrate hosts. He has used genetic approaches to conduct pioneering work that spawned six related areas of research: the evolution and regulation of Rhizobium genes involved in symbiotic nitrogen fixation; the regulation of Rhizobium genes by two-component regulatory systems involving histidine kinases; the establishment of Arabidopsis thaliana as a worldwide model system; the identification of a large family of plant disease resistance genes; the identification of so-called multi-host bacterial pathogens; and the demonstration that Caenorhabditis elegans has an evolutionarily conserved innate immune system that shares features of both plant and mammalian immunity.Open in a separate windowFrederick M. AusubelI was born on VJ day, September 2, 1945, the official end of World War II and the first day of the baby boomer generation. It was an auspicious time for a future scientist to be born. I entered the job market in 1975 when interest in and funding of science was expanding and when academic jobs were relatively plentiful.The path I have taken from being a college chemistry major to a molecular biologist and geneticist has had many twists and turns. Chance encounters and unplanned events played an important role in shaping my career. The political and social upheavals of the 1960s also greatly influenced my career choices, as did a psychological restlessness that made it difficult for me to focus for any extended period on a particular project or goal. Although I would not necessarily recommend that anyone follow my career path, I suspect it would be a much more treacherous journey today than it was 50 years ago, reflecting what appears to me to be a degradation in the ethos of the scientific community.     

It's a Wonderful Life: A Career as an Academic Scientist

Many years of training are required to obtain a job as an academic scientist. Is this investment of time and effort worthwhile? My answer is a resounding “yes.” Academic scientists enjoy tremendous freedom in choosing their research and career path, experience unusual camaraderie in their lab, school, and international community, and can contribute to and enjoy being part of this historical era of biological discovery. In this essay, I further elaborate by listing my top ten reasons why an academic job is a desirable career for young people who are interested in the life sciences.Students are attracted to careers in academic science because of their interest in the subject rather than for financial reward. But then they hear messages that make them think twice about this career choice. It is difficult to find a job: “Hear about Joe? Three publications as a postdoc and still no job offers.” The NIH pay line is low: “Poor Patricia, she is now on her third submission of her first NIH grant.” Publishing is painful: “Felix''s grad school thesis work has been rejected by three journals!” Academic jobs are demanding: “Cathy has spent her last three weekends writing grants rather than being with her family.”Such scenarios do take place, but if you think that this is what a career in academic science is about, then you need to hear the other side of the story. And this is the purpose of this article—a chance to reflect on the many good things about the academic profession. In the classic movie It''s a Wonderful Life, George Bailey is at the point of despair but regains his confidence through the wisdom and perspective of a guardian angel, Clarence. Doubt and setbacks also are bound to happen in science (as is true of other careers), but pessimism should not rule the day. It is a great profession and there are many happy endings. I would like to share my top ten reasons of why being an academic professor is a “wonderful life,” one that bright and motivated young people should continue to aspire to pursue.     

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.     

Basic versus applied research: Julius Sachs (1832–1897) and the experimental physiology of plants

The German biologist Julius Sachs was the first to introduce controlled, accurate, quantitative experimentation into the botanical sciences, and is regarded as the founder of modern plant physiology. His seminal monograph Experimental-Physiologie der Pflanzen (Experimental Physiology of Plants) was published 150 y ago (1865), when Sachs was employed as a lecturer at the Agricultural Academy in Poppelsdorf/Bonn (now part of the University). This book marks the beginning of a new era of basic and applied plant science. In this contribution, I summarize the achievements of Sachs and outline his lasting legacy. In addition, I show that Sachs was one of the first biologists who integrated bacteria, which he considered to be descendants of fungi, into the botanical sciences and discussed their interaction with land plants (degradation of wood etc.). This “plant-microbe-view” of green organisms was extended and elaborated by the laboratory botanist Wilhelm Pfeffer (1845–1920), so that the term “Sachs-Pfeffer-Principle of Experimental Plant Research” appears to be appropriate to characterize this novel way of performing scientific studies on green, photoautotrophic organisms (embryophytes, algae, cyanobacteria).     

Science: priceless,but costly

Working as a researcher is very satisfying. However, it comes with a price. This is a story about growing up as a scientist in the field of molecular biology. Starting as a young, rather naive researcher, I learned, step by step, not only the facts about my favorite RNA molecules but also the demands and downsides of academia. Going through my recent “scientific awakening,” I fully acknowledged the rules of the game: to write, to publish, to patent, to apply for grants and awards, and finally, to engage in all forms of coscientific endeavors. After going through a divorce, single parenting, immigration, and being scooped, I became a scientist who finally takes her career in her own hands and navigates through, but does not succumb to, the difficulties in science. This is my monument to resilience.     

Training matters! Narrative from a Black scientist

As STEM (Science, Technology, Engineering, and Math) professionals, we are tasked with increasing our understanding of the universe and generating discoveries that advance our society. An essential aspect is the training of the next generation of scientists, including concerted efforts to increase diversity within the scientific field. Despite these efforts, there remains disproportional underrepresentation of Black scientists in STEM. Further, efforts to recruit and hire Black faculty and researchers have been largely unsuccessful, in part due to a lack of minority candidates. Several factors contribute to this including access to opportunities, negative training experiences, lack of effective mentoring, and other more lucrative career options. This is a narrative of a Black male scientist to illustrate some of the issues in retaining Black students in STEM and to highlight the impact of toxic training environments that exists at many institutions. To increase Black participation in STEM careers, we must first acknowledge, then address, the problems that exist within our STEM training environments in hopes to inspire and retain Black students at every level of training.

I write this today as the curtain of systemic racism and oppression has lifted on our nation. I write this today knowing that difficult conversations about race are happening all across America. As a result of tremendous sacrifices and lives lost, there have been demonstrations and rallies internationally demanding change, prompting governments, organizations, and companies to issue statements claiming that Black Lives Matter (Asmelash, 2020). While the rage has sparked the demand for equity in our society, what does this mean for science?My heart is heavy with these discussions as I have reflected on my own journey in science and revisit the toxic environment that often makes up our science culture. The journey has been long and brutal. It has taken me from first realizing that I wanted to become a scientist, to having this dream deferred by racism, to adopting a persona of persistence and resilience, and finally becoming a professor and cell biologist. This trek through science is one that is not traversed by many Black people (Graf et al., 2018).When confronted by the pervasiveness of racism in science, I remember surviving the assault by learning about the resilience story of Carl Brashear (Robbins, 2000). In 1970, Master Chief Petty Officer Brashear became the first African American master diver in the Navy, and he showed unwavering strength and persistence in the face of racism. Brashear faced an onslaught of racism during his training that endangered his life countless times, but he persisted and eventually won the admiration of his fellow divers. Upon reflection, his story has many signs of an abusive hazing relationship. However, at the time, I thought emulating his behaviors of persistence was the answer to success in science. I thought, “All you have to do is not give up.” I focused on what I thought I could control and kept the Japanese proverb, “Fall down seven, stand up eight” above my bench. I worked long hours, made many mistakes, but always got right back up to the bench to try again. I never saw myself as the brightest or smartest, but I would tell myself “I will be the one who does not give up.” When I recall these stories and talk to students about my journey, I would always say I wanted to be like the cockroach. Because, as is commonly known, you can never get rid of the cockroach. What I never realized with this persistence or “grit” mentality was that it never addressed the problems of systemic racism within the culture of science (Das, 2020). This message of persistence is akin to blaming the victim and not dealing with the root problems in science, including the lack of mentoring, implicit bias, and hostile teaching and training environments (Barber et al., 2020; Team, 2020).In her book, We Want to Do More Than Survive, Bettina Love talks about the idea of teaching persistence or “grit” to African American students as the educational equivalent to the Hunger Games, a fictional competition where participants battle to the death until there is only one victor (Love, 2019). Instead of addressing institutional barriers to success for African Americans in science (i.e., dismantling the Hunger Games arena), we prepare them to survive in a toxic environment. We tell African American students at a young age that the system is structured against them and that they have to be twice as good and work twice as hard as white students (Thomas and Wetlaufer, 1997; Cavounidis and Lang, 2015; Danielle, 2015). We heap a tremendous amount of pressure and responsibility on their shoulders without ever addressing the question, why is it like this? We are in effect training them for the Hunger Games. As they enter college as science majors, they are pitted against each other, and the few victors move into science careers.This Hunger Games analogy (Love, 2019) is reflective of my thinking early on in my science career. As a freshman marine biology major, I imagined myself, like Brashear, a soldier during basic training. I was a member of the “people of color” (POC) squad that was given the least amount of resources and the most dangerous duties. As part of the POC squad, we moved forward through our college years. I saw many fellow soldiers drop from science, and there were only a handful of us left when I reached my junior year (Koenig, 2009).Recently, Michael Eisen, Editor-in-Chief of eLife, authored an opinion article entitled “Racism in Science: We need to act now” (Eisen, 2020). In this article, he reflected on the current racial climate in science and examined his role as both a principle investigator (PI) of a research laboratory and an editor of a prestigious journal. Of note, he highlighted the dire lack of African Americans he had worked with over his career, including the number of researchers he trained in his laboratory, senior editors, and even reviewers for the articles sent for publication to eLife. I appreciated his honesty in shedding light on the issue that so many people whisper about in department hallways or during coffee breaks at national conferences. Based on my journey, I truly understand this lack of diversity, as so few of us are victors in the scientific Hunger Games.As we struggle as a nation with the role of policing within our society, I find similarities between aggressive policing in the Black community and training of Black and Brown students (North, 2020). There are strong implicit biases that we hold within our training environment, and Black students usually find themselves very quickly judged (or prejudged) for a perceived lack of commitment, motivation, or focus (Park et al., 2020). They are also stereotyped as lacking in quantitative abilities (especially the ability to do math) (McClain, 2014). Taken together, these biased judgements result in a lack of trust regarding their data (Steele, 1997). In other words, research supervisors may implicitly expect Black students to be untrustworthy. This is extremely problematic because educational research shows that one of the greatest determinants of students’ success is their teachers’ expectations (Boser et al., 2014). Consequently, it is predictable that if research supervisors expect Black students to be untrustworthy, they will fail.As PIs, we must trust our research students because they are extensions of ourselves in the laboratory. Due to our inability to spend significant amounts of time at the bench, we must trust our students to figure it out and get the work done. Inevitably, experimental approaches will fail; however, based on my experiences in science, Black students are often not given the benefit of the doubt. Instead, I have seen mis/distrust of their commitment, values, and abilities that creates the narrative that they are not motivated, do not care about science, and/or are unable to get the work done, resulting in a broken trainer/trainee relationship. I have witnessed too many Black students fall victim to a “one strike” policy. This was true of me in my early training in marine biology, where I was asked to leave after only 6 months of working in a laboratory. The professor suggested that I had a lack of commitment to my project and was told by other lab members that they collected “my” data, thus providing justification to ask me not to continue. However, what the professor did not know (or care to ask about) was that the other lab members deemed me as someone who did not belong. Consequently, without my knowledge, they collected data on my project and sent it to the PI, thereby working to reinforce the narrative of my lack of commitment. This experience significantly hindered my access to research opportunities and blacklisted me from any other marine biology labs at my university because I was labeled as uncommitted to science. This ended my career in marine biology. I lost the Hunger Games.As a graduate student, I found another opportunity in a cell biology laboratory, and I tried to apply lessons learned from my earlier participation in the Games. I overcommitted to lab work, blocking out any activities related to my culture or personal life. Instead, I dedicated myself completely to the lab. Working 12-h days, I found that my research was progressing, but I was burning out and losing any desire toward a research career. In particular, my burnout was connected to the perception that any interest in my culture and community would not be allowed or accepted or would signal a lack of adequate commitment to science. In effect, I was learning that being a scientist meant that I could not be Black. This, coupled with the constant microaggressions that I faced from professors in classes, among my graduate cohort, and my laboratory colleagues, broadcasted the message that I was an intruder in science. Luckily, I received good mentoring and advice on how to succeed in my graduate program, learning that it was not a sprint, but a marathon. I learned how to balance my personal and professional life, and I always kept them separate. Additionally, the mental image of the resilient cockroach helped me repeatedly during my graduate training, from failing my qualifying exams and failed experiments at the bench to rejections of papers and fellowship applications. While all scientists know that being a scientist means accepting significant amounts of failure, I could not help but feel that the failures I experienced were more frequent, more recognized by others, and even expected by some. This culture of expected failure for people of color (i.e., presumed incompetence), combined with implicit biases and microaggressions, can establish significant barriers for entering and staying in STEM training environments (Smith et al., 2007).To overcome barriers to success in STEM, I worked hard to become a professor in cell biology. I believed that as a professor, I could make a difference, change the environment, and contribute to the change that is so desperately needed. However, I have discovered that the current science culture is just as toxic as when I was a student. Yes, there are programs targeting the inclusion of historically underrepresented groups. There are also a growing number of institutions that are adopting inclusive teaching strategies. Further, we are seeing hiring committees require diversity statements from their applicants as well as receiving implicit bias trainings (Wood, 2019). However, there remains nearly a complete lack of Black faculty members at universities and colleges (Jayakumar et al., 2009; Garrison, 2013; Li and Koedel, 2017). This is, in part, because we have not changed the systemic racism that exists within our training environments. In fact, this racism comes from our noninclusive faculty bodies (Hardy, 2020). In essence, we have nearly a complete absence of Black faculty in STEM because so few Black trainees survive the Hunger Games. More troubling, if they survive, they may be found otherwise unacceptable.Changing the system starts with the belief that Black students can be scientists, followed by acting to proactively encourage and support Black students in STEM. As Eisen states, “This is a solvable problem, we have chosen not to solve it” (Eisen, 2020). Recruiting Black students and scientists at every level is a good start, but without changing the scientific environment to be more welcoming and affirming, those recruited to science will continue to be traumatized. In other words, while increasing access to science is required, it is not sufficient. The dominant majority in science also needs to identify and address their own biases to create antiracist environments. This will only happen when scientists from all groups recognize our convergent interests to advance our universal missions, which is to increase our understanding of the world around us and to solve research questions that will benefit our communities. This is best achieved by a diverse and inclusive scientific workforce for greater knowledge, discovery, and innovation.     

Hongyuan Yang: Tracking lipids,one droplet at a time

Hongyuan Yang investigates lipid trafficking and lipid droplet biogenesis.

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

The ‘root-brain’ hypothesis of Charles and Francis Darwin: Revival after more than 125 years

This year celebrates the 200^th aniversary of the birth of Charles Darwin, best known for his theory of evolution summarized in On the Origin of Species. Less well known is that, in the second half of his life, Darwin’s major scientific focus turned towards plants. He wrote several books on plants, the next-to-last of which, The Power of Movement of Plants, published together with his son Francis, opened plants to a new view. Here we amplify the final sentence of this book in which the Darwins proposed that: “It is hardly an exaggeration to say that the tip of the radicle thus endowed [with sensitivity] and having the power of directing the movements of the adjoining parts, acts like the brain of one of the lower animals; the brain being seated within the anterior end of the body, receiving impressions from the sense-organs, and directing the several movements.” This sentence conveys two important messages: first, that the root apex may be considered to be a ‘brain-like’ organ endowed with a sensitivity which controls its navigation through soil; second, that the root apex represents the anterior end of the plant body. In this article, we discuss both these statements.Key words: auxin, cognition, plant neurobiology, plant tropisms, roots, sensory biology, signaling     

Biophysical Reviews’ “Meet the Councilor Series”—a profile of Peter Pohl

It is my pleasure to write a few words to introduce myself to the readers of Biophysical Reviews as part of the “Meet the Councilor Series.” Currently, I am serving the second period as IUPAB councilor after having been elected first in 2017. Initially, I studied Biophysics in Moscow (Russia) and later Medicine in Halle (Germany). My scientific carrier took me from the Medical School of the Martin Luther University of Halle-Wittenberg, via the Leibniz Institute for Molecular Pharmacology (Berlin) and the Institute for Biology at the Humboldt University (Berlin) to the Physics Department of the Johannes Kepler University in Linz (Austria). My key research interests lie in the molecular mechanisms of transport phenomena occurring at the lipid membrane, including (i) spontaneous and facilitated transport of water and other small molecules across membranes in reconstituted systems, (ii) proton migration along the membrane surface, (iii) protein translocation, and (iv) bilayer mechanics. Training of undergraduate, graduate, and postdoctoral researchers from diverse academic disciplines has been—and shall remain—a consistent part of my work.

     

A 20-year encounter with the imposter syndrome

Both in their formative years and later careers, some scientists suffer from something more than occasional self-doubts. There is a more severe affliction that strikes many more than was once realized. Here I reflect on my encounter, in the hope that sharing it can be of some value.

A landmark study 42 years ago presented the results of a survey of 150 highly successful women professionals as regards their self-assessment of confidence. The results were stunning. Many subjects gave responses revealing moderate to intense emotional stress and anxiety as to their qualifications. To characterize this revealed broad experience, the authors coined the term “the imposter syndrome” (Clance and Imes, 1978). It was apt indeed, the first word conveying the haunting sense of being an intruder in the guild, unqualified, and in the game only by some fluke; the second term meaning that the condition was encountered as a constellation of effects, from heart to mind to gut, with fear the signal transduction onto all those centers. This study was a turning point, inter alia, in the broadening field of scholarship examining the barriers to women in the workplace.At the time of the Clance and Imes publication it was not known if this same affliction occurs in men and, if so, with what prevalence, or whether it occurs in some professions more than others. In at least the sciences, it now appears that both females and males encounter it, both as students and as young trainees, although the prevalence is less well known for males. I have no expertise in this field beyond my one experience, which I share here in the hope that it may have some nugget of value for all those who doubt their talent.Science was not my first love academically. I had no butterfly collection, nor did I conduct explosion-seeking chemistry experiments in the cellar. My favorite subject in high school was Latin, my least favorite was biology. I remember a lecture on vitamins in the latter course, where we had to memorize what happens when each one is missing or limiting in the diet. We asked the teacher for an explanation for pellagra, scurvy, and so forth (meaning: what do these vitamins do?). He replied, “They are essential.” QED. (But in fairness, this teacher could be better sometimes—for example, he told us why the mouthwash “Listerine” was so named.)After studying English and Latin in college, I came to biology for a second try and it felt better. I applied to medical school but declined my acceptances and went for a Ph.D. During this time, I do not recall feeling particularly anxious about my abilities, although I had not yet really done anything to reveal their presence or absence. I do recall a few times when I was nervous, but that is not uncommon for graduate students. But one day, I got the first sensation of perhaps something more. It was my Ph.D. qualifying exam in the Department of Zoology at Syracuse University, in 1961. One part was a four-hour written exam in one’s field, the other was a free-for-all with the whole faculty asking about anything under the sun in biology. At one point I was asked to derive the Nernst equation (describing a cell’s membrane resting potential). I replied “OK, but from what?” The faculty member thought I was being evasive, but I was just looking for a little guidance (as when the Scripps–Howard Spelling Bee contestant asks the moderator: “Can you please use that in a sentence?”) I knew one cannot get the Nernst equation from f = ma, there is an electrical component (duly named for Michael Faraday). I managed to get through this question and all the others, but it was then I began to wonder if I was playing some charade. Maybe I had been clever but not really grounded. That I had gotten through the oral exam didn’t quiet my sense that I might have “pulled something off” and maybe hadn’t deserved to have passed. That was the moment when a visitor first arrived in my consciousness. It whispered, “You know, Thoru, it’s just possible that you might be a phony.”During my postdoc this nagging feeling got stronger. I had moved from a very good zoology program at Syracuse to an elite department of cell biology at the Albert Einstein College of Medicine. My work was going well, but all the people around me seemed so much smarter and their research seemed more significant. On one side of the lab I was in, Phillip Coffino, an M.D./Ph.D. student, was measuring the somatic mutation rate of immunoglobulin genes with Matthew Scharff, and on the other side, Ellie Ehrenfeld was isolating the poliovirus RNA replicase in the laboratory of Donald Summers. These were pioneering projects and I was in awe of both them and their science. By the time I left Einstein my case of the imposter syndrome had reached the point where I felt lucky to get an independent position.Today, I reflect on all this. First, and as conveyed in the original study, was the certitude in my assessment of myself. At the time this affliction had me in its maw, no one could have convinced me otherwise. As other victims of this condition have attested, the sense that it is totally true is overwhelming. The second feature of the imposter syndrome, as was also revealed in the study, was that the day was just around the corner when I would be found out. This evokes a pattern of paranoia where, on each and every day, one is just waiting for “the truth” to come out.But then, when I was 40, I got over this thing. It was quite sudden. I was on my way to Caltech to give a seminar and looked out the window over Kansas at the puffed popcorn of white clouds and got a simple idea, a question that should always be asked by any scientist. What if I were wrong? What if I were misinterpreting the data? For the first time, looking out that airplane window, it came to me that the obsession that I was totally incompetent was not supported by the facts, and that a hypothesis that I was at least competent in a “guild-average” sense seemed to be at hand.How the imposter syndrome affects females vs. males is still being studied. I do think that when it hits males, we compensate in ways that are different from females. One of the most compelling books in this field describes an intrepid group of women who provided powerful anchors for each other (Daniell, 2008). They were not all suffering from the imposter syndrome, but rather receiving the totality of slings and arrows that professional women face on many fronts. This landscape of inquiry and scholarship is worthy of further investigation as we seek to understand the degrees to which gender differentially influences the aspirations of all those coming up, and to which the imposter syndrome is an infection that may have no host restriction as to gender or ethnicity. The key question now, more than four decades after the landmark study, is whether the imposter syndrome has afflicted all genders and ethnicities to similar or differing degrees, and not only in America and not just in the sciences. This is the total perspective in which this career-inhibitory/destructive phenomenon must be understood, to elevate our ability to mentor, and if possible “vaccinate,” all students and emerging young professionals who suffer from it. Only when we all understand the roots of the phenomenon’s existence in the first place can we do our best to stamp it out.     

Review of the Parasa undulata (Cai, 1983) species group with the first conifer-feeding larva for Limacodidae and descriptions of two new species from China and Taiwan (Lepidoptera,Limacodidae)

Although the caterpillars are well-known for the stings and magnificent coloration, the systematics of Limacodidae is historically neglected and chaotic due to the difficulty in matching the larval with adult stages as well as the very conservative and convergent adult morphology. One of the biggest taxonomic problems surrounds a collective group from Southeastern Asia, termed the “green limacodid moths”, which harbours at least 90 species placed in the genus Parasa Walker, 1859 and 14 “subunits”. The P. undulata group was previously composed of 3 species from China and Taiwan, and characterized only by wing pattern. This species group is extensively studied herein with two new species described, i.e. P. viridiflamma sp. n. (Taiwan) and P. minwangi sp. n. (S. China), and discovery of female genitalia of three species, presenting new phylogenetic insights in this potentially paraphyletic genus. In addition, one limacodid larva was found to be feeding exclusively on Picea (Pinaceae) in Taiwan. Its identity, Parasa pygmy Solovyev, 2010 in P. undulata group, is confirmed through matching its COI sequence to the adult. This discovery is also biologically significant because the previous known host breadth of Parasa was of polyphagy on various angiosperm plant families. This case, therefore, represents the first record of conifer-feeding behavior in this family as well as the first of specialized herbivory in the genus. Meanwhile, the background match between Picea leaves and larval coloration is shared with other Picea-feeding insects. This phenomenon is worth of further investigation in the aspect of convergent evolution of crypsis associated with a particular plant.     

A new genus for a rare African vespertilionid bat: insights from South Sudan

A new genus is proposed for the strikingly patterned African vespertilionid “Glauconycteris” superba Hayman, 1939 on the basis of cranial and external morphological comparisons. A review of the attributes of a newly collected specimen from South Sudan (a new country record) and other museum specimens of “Glauconycteris” superba suggests that “Glauconycteris” superba is markedly distinct ecomorphologically from other species classified in Glauconycteris and is likely the sister taxon to Glauconycteris sensu stricto. The recent capture of this rarely collected but widespread bat highlights the need for continued research in tropical sub-Saharan Africa and in particular, for more work in western South Sudan, which has received very little scientific attention. New country records for Glauconycteris cf. poensis (South Sudan) and Glauconycteris curryae (Gabon) are also reported.     

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.     

The Distribution of the Asymptotic Number of Citations to Sets of Publications by a Researcher or from an Academic Department Are Consistent with a Discrete Lognormal Model

How to quantify the impact of a researcher’s or an institution’s body of work is a matter of increasing importance to scientists, funding agencies, and hiring committees. The use of bibliometric indicators, such as the h-index or the Journal Impact Factor, have become widespread despite their known limitations. We argue that most existing bibliometric indicators are inconsistent, biased, and, worst of all, susceptible to manipulation. Here, we pursue a principled approach to the development of an indicator to quantify the scientific impact of both individual researchers and research institutions grounded on the functional form of the distribution of the asymptotic number of citations. We validate our approach using the publication records of 1,283 researchers from seven scientific and engineering disciplines and the chemistry departments at the 106 U.S. research institutions classified as “very high research activity”. Our approach has three distinct advantages. First, it accurately captures the overall scientific impact of researchers at all career stages, as measured by asymptotic citation counts. Second, unlike other measures, our indicator is resistant to manipulation and rewards publication quality over quantity. Third, our approach captures the time-evolution of the scientific impact of research institutions.