Support for a career in science

I am so very honored to receive the Women in Cell Biology Sandra K. Masur Senior Leadership Award from the American Society for Cell Biology (ASCB), particularly because many of the previous awardees have served as mentors and sources of inspiration throughout my own career. I also thank the ASCB for always striving to be maximally inclusive, in terms of both the scientists it supports and its broad vision of what constitutes cell biology. As a graduate student I gave one of my first talks at an ASCB meeting, and I am proud to have been an ASCB member for almost 30 years. In this essay, I describe my own career to illustrate the support that I believe is needed to achieve a career in science.

S. L. Wolin     

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.     

Reminiscences,collaborations and reflections

This is a personal account by a semi old-timer who completed his official term as a professor of plant biochemistry at Nagoya University in Japan in 1992. My university student life began soon after the World War II (1948). I shared the hardships of many in my age group, in that life was difficult during my college years. I was fortunate to have the opportunity of studying in the USA on a Fulbright scholarship first at Purdue University (1955–1956), and then at the University of California, Berkeley (1956–1957). My graduate study and postdoctoral training in the new world were vitally refreshing and stimulating, which gave me the impetus for becoming a natural scientist associated with academic institutions. Consciously and subconsciously I was impressed by the friendly and liberal atmosphere surrounding young students as well as senior scholars in the United States. But more importantly, I was inspired by the critical and competitive minds prevailing among these people.The appointment as a biochemist at the International Rice Research Institute (IRRI) in the Philippines (1962–1964) was the real start of my professional career. The work was continued upon my return to Nagoya to become a staff member of the Research Institute for Biochemical Regulation (1964–1992). Throughout the years, my major research interest has covered photosynthesis as a whole, involving photosynthetic CO₂-fixation (RuBisCO), carbohydrate metabolism, e.g. starch biosynthesis and breakdown (-amylase), and metabolic regulation, which are interrelated in the basic metabolism of plant cells.I shall briefly describe in this article highlights from my studies and discoveries made and I shall also discuss their possible significance in plant metabolism, with the hope that it does not contradict my sense of humility: They are (a) discovery of ADPG in plants and its role in starch biosynthesis; (b) structure-function relationship of RuBisCO proteins, in particular on heterologous recombination of their subunits of plant-type enzyme molecules derived from the prokaryotic photosynthetic bacteria; (c) molecular evolution of RuBisCO genes; (d) mode of actions (formation, intracellular transport and secretion) of rice seed -amylase and its structural characteristics (distinctive glycosylation), and (e) DNA methylation and regulatory mechanism of photosynthesis gene expression in plastids (amyloplasts). In each step of my research, I shared joy, excitement, disappointment, and agony with my colleagues, an experience that may be common to all researchers. Although it is now becoming well recognized among the scientific community in Japan, I want to point out that interaction of multinational scientific minds in the laboratory produces a vital and creative atmosphere for performance of successful research. I experienced and realized this important fact in my earlier days in the USA and the Philippines. Inasmuch as I believe that this is the most crucial element for any research laboratory to possess, I fondly remember the friendships gained with numerous overseas visitors and collaborators who have contributed immensely to our work.Written at the invitation of Govindjee.     

Looking back on a life of unacknowledged privilege and a call to action

The year 2020 provided a wake-up call about the role systemic racism plays in shaping our nation and shaping science. While hard work and great mentors helped bring me a long way from a farm in Minnesota, it’s become much clearer that the privilege of being white and male and the accumulated advantages that began there played powerful roles. It’s time for white scientists like me to listen, think, and take action.

We all have personal stories that we use to describe our trajectory in life and science. For the past five decades the narrative I told myself was a simple one of good luck, hard work, support from my community, and mentors at pivotal times. However, in many important ways, this was just a small part of the truth, ignoring the role unperceived privilege played. The many underlying injustices that were laid bare in our nation this past year began to open my eyes, prompting me to look back at the roles hidden privilege played in my career and the power that these have given me. This challenged me to use the power of that privilege to speak and act to try to change the system in which engrained advantages benefit some but not all. I am telling my story in hopes it will encourage my white colleagues to examine their own.     

TLR4 inhibits mesenchymal stem cell (MSC) STAT3 activation and thereby exerts deleterious effects on MSC-mediated cardioprotection

Background

Bone marrow-derived mesenchymal stem cells (MSC) improve myocardial recovery after ischemia/reperfusion (I/R) injury. These effects are mediated in part by the paracrine secretion of angiogenic and tissue growth-promoting factors. Toll-like receptor 4 (TLR4) is expressed by MSC and induces apoptosis and inhibits proliferation in neuronal progenitors as well as many other cell types. It is unknown whether knock-out (KO) of TLR4 will change the paracrine properties of MSC and in turn improve MSC-associated myocardial protection.

Methodology/Principal Findings

This study explored the effect of MSC TLR4 on the secretion of angiogenic factors and chemokines in vitro by using ELISA and cytokine array assays and investigated the role of TLR4 on MSC-mediated myocardial recovery after I/R injury in an isolated rat heart model. We observed that MSC isolated from TLR4 KO mice exhibited a greater degree of cardioprotection in a rat model of myocardial I/R injury. This enhanced protection was associated with increased angiogenic factor production, proliferation and differentiation. TLR4-dificiency was also associated with decreased phosphorylation of PI-3K and AKT, but increased activation of STAT3. siRNA targeting of STAT3 resulted in attenuation of the enhanced cardioprotection of TLR4-deficient MSC.

Conclusions/Significance

This study indicates that TLR4 exerts deleterious effects on MSC-derived cardioprotection following I/R by a STAT3 inhibitory mechanism.     

A fortunate period of overlap with Prof. Haruki Nakamura

The author recounts a period of overlap with Prof. Haruki Nakamura that stretched from 2007 till the present day. Starting as a short-term research fellow in his laboratory, the author has also been a coauthor, academic colleague, and joint journal editorial board member of Prof. Nakamura.

I first met Prof. Haruki Nakamura in June of 2007 after coming to Osaka to talk with him about the possibility of taking on a short-term research position in his laboratory. At that stage, he was the Professor in charge of the Laboratory for Bioinformatics and Computational Structural Biology located within the Institute for Protein Research (IPR) at Osaka University as well as the Director of the Protein Data Bank in Japan (PDBj)—the Asian hub of the worldwide PDB. Since that time, he has been an interesting constant in my life and is someone that I have come to admire as much for his character and work ethic as for his scientific prowess, the latter of which is truly remarkable. In this Commentary, I thought I might recount some of the interesting ways my scientific career has intertwined with Prof. Nakamura’s, hopefully shining a light on some of the positive ways that scientists can interact with each other as well as highlighting some of the points that I genuinely admire about Prof. Nakamura.     

A year since George Floyd

The murder of George Floyd sparked an awakening, long overdue, which reverberated throughout society. As science begins to acknowledge its role in perpetuating systematic racism, the voices of Black scientists, which have largely been absent, are now being called on. As we rightly begin to make space for diverse voices and perspectives in science, we all must think about what it is we are asking minoritized individuals to do.

It has been roughly 1 year since the murder of George Floyd, an unarmed Black man, who was killed over an alleged counterfeit 20 dollar bill in Minneapolis, Minnesota (Hill et al. 2020; Kaul, 2020; Levenson, 2021). In many ways, his murder was no different than the murders of thousands of other murders of Black people in this country (Thompson, 2020; Lett et al., 2021; Tate et al., 2021). However, what distinguishes George Floyd’s murder from many other high profile cases is that it was unambiguously captured on video (Alexander, 1994), an act of bravery by Darnella Frazier, a 17-year-old Black woman (Izadi, 2021), at a time when the world was mostly housebound by a raging global pandemic. As a result, his murder reverberated through society in a way that has not happened in my lifetime. While there have been other high profile cases of murders carried out by police (Treyvon Martin, Walter Scott, Breonna Taylor, and Philando Castile, among many others), these cases failed to fully sustain the attention of a national and international audience (Chan et al., 2020; Chughtai, 2021). The murder of George Floyd was fundamentally different, and for once, more than just Black people were paying attention. His murder sparked protests across the nation led by the Black Lives Matter (BLM) movement (Day, 2015; Taylor, 2016; Banks, 2018; Taylor, 2021), and the demands for change were so loud people could not help but hear.As a Black, gay man who is also a scientist, I was thrown into despair. All of my life I have thought if I just worked hard enough, if I am kind and unthreatening, if I play the game and keep my head down, maybe I can make it in academia. Maybe then I will be seen and accepted, not just by society, but by the scientific community. George Floyd’s murder reminded me, and many of my Black colleagues, that our degrees can’t protect us, that our privileged middle-class upbringing (if we had one) was not a shield. Our lives were not worth more than a counterfeit 20 dollar bill.Science, which has always been a product of society, was not impervious to these reverberations. By late June my inbox began to slowly fill with invitations to speak at several institutions for their seminar series, retreats, or special symposia. It felt as if the scientific community, for the first time, realized that there were Black scientists among them. In the throes of my own despair, and the feeling that I needed to be doing something for my community, I began to say “yes.” I was not going to participate in the nightly protests that occurred in my newly adopted hometown of Portland, Oregon. Aside from fearing I could be next to lose my life at the hands of the police (Edwards et al., 2019), these protests were happening in the backdrop of a global pandemic. I came to the conclusion that by accepting these invitations to speak, this could be my activism, my way of sparking change, increasing visibility, and being seen not only for my own sake but also for other Black scientists.Before I write anything else, I want to be clear: I am extremely thankful to all the institutions and organizations that invited me and gave me a platform. I am extremely proud of my students’ work and of the research we produce. I am sharing my experiences with the hope that they can be instructive to the greater scientific community, but if I am being frank, there is a bit of anger.I received over 15 invitations and gave an additional three or four interviews over the course of the year. Most of these came with the expectation that I would also talk about my work in Diversity, Equity, and Inclusion. But here’s the lowdown: prior to this year, I did not view myself as someone who did Diversity, Equity, and Inclusion work. I am co-chair of the LGBTQ+ committee of the American Society of Cell Biology and a member of the Diversity, Equity, and Inclusion committee of the Genetics Society of America. I volunteer for both of these committees because they speak to something I care deeply about, the advocacy for minoritized ¹ scientists. I also embody both of these axes of diversity; so, in some way, I am only looking out for myself. This is far from being a scholar or doing “Diversity work.” I fully recognize that there are individuals who have dedicated their lives to this type of work with entire academic fields populated with accomplished scholars. So, I started this year of talks being invited because I am a Black, gay scientist at a time when science was grappling with its own systematic racism, under the guise of my nonexistent Diversity, Equity, and Inclusion work.What has this year actually taught me? The first thing it taught me is that I have been missing out. Prior to George Floyd’s murder, I had only received three seminar invitations from major research institutions and unfortunately all within a year of being posttenure. That is after nearly 6 years in my current position.In giving these talks I got the opportunity to meet with some of the giants in my field, people I have looked up to for years. I received reagents, offers to collaborate, and a litany of great ideas that will help drive my research program for years to come. I left some of these meetings truly inspired and excited to start experiments. These opportunities would have been invaluable to me, pretenure. One could argue, I did not need it. I made it even without this networking and the advantages these visits bring. Before you applaud my ability to persist and be resilient, we should take a deep look at the systems that have forced people who look like me to be doubly resilient. If George Floyd had not been murdered, would any of these invitations have happened? If the previous 6 years are any indication of a trend, I would have to say most certainly not. Why did it take a murder and the reignition of a Civil Rights movement for me to have the type of interactions I now know many of my straight, white counterparts have had from the very beginning of their independent careers? Let me be clear: this is a form of systematic racism, plain and simple.As I began to make the rounds, I was often asked to either share a bit of my journey or include my Diversity, Equity, and Inclusion work in my talks. This sometimes came at the expense of sharing my lab’s work. While I was very happy to do so, this was very much implicit in the invitations I received. At times it did feel that my inclusion was only checking a box, placating the graduate students so that they could see that their department or institution was responding to their demands. This also had the consequence of making me feel as though my science was merely performative. I was being invited to do the Diversity work institutions did not want to do. This is the tension I, and many other minoritized scientists, face. I want to share my experiences with the hopes that the next generation will have it better; but, my scholarly work is not in Diversity, Equity, and Inclusion. I fully recognize that it is my embodied diversity that is bringing me to the table; but, it is the science I want to share.On the first invitation to give a seminar, I promised myself that I was going to be honest. This meant that I would tell the truth about my experience and bare my soul over and over again. What I had not counted on was the emotional toll this would take on me. Reliving my own trauma, on a regular basis, left me emotionally drained after these visits. In one of my “stops” (I use quotes here because these “visits” were all virtual), I met with the queer, person of color (POC), graduate students. This session quickly turned into an emotional support group where I heard stories of mistreatment, racism, and discrimination. It was nearly impossible to maintain my composure. Diversity, Equity, and Inclusion work is clearly extremely important, but, maybe, we could just start by listening to the needs of the students and having a bit of humanity.The trial of Derek Chauvin has come and passed, and much to my surprise, and to the surprise of many other Black people nationwide, he was found guilty and was sentenced to prison (Arango, 2021; Cooper and Fiegel, 2021). This, of course, is not justice, not even close. Justice would mean that George Floyd is still alive and would get to live out his life in the way he chose. We are also at the beginning of the end of the pandemic. In 6 months or less, we may all be returning to life, more or less, as it was before George Floyd, before COVID-19. Does this mean we stop fighting? Does this mean that I, and many other Black scientists, suddenly disappear? For George Floyd, for countless other faceless Black people before him, I sincerely hope not. We need to continue to give Black scientists a platform. We need to ensure that they, too, are given the opportunity to network, collaborate, and interact with the larger scientific community. This means the invitations cannot stop. To further this, we need to ensure that Black scientists are included in every grant review panel, are included on speaker lists at every national and international meeting, are funded, and are in the room where funding, tenure, and other critical decisions are being made. We need to recognize that systematic racism has not gone away with Derek Chauvin’s conviction and sentencing. We need to continue to push forward. And, for all of you young, minoritized scientists (and allies) reading this, demand change and do not take "no" for an answer. I am truly sorry this has fallen on your shoulders, but enough is enough. The next generation of minoritized scientists should be recognized for their science without the additional burden of creating their own space.About the AuthorI am currently an Associate Professor of Biology at Reed College (https://www.reed.edu/biology/applewhite/index.html), which is located in Portland, Oregon. I arrived at Reed in 2014; prior to that, I was a postdoctoral fellow at the University of North Carolina, Chapel Hill. I received my PhD from Northwestern University in Cellular and Molecular Biology and a BS in Biology from the University of Michigan where I was also a 4-year letter winner in track and field. My research focuses on the cytoskeleton where I study cell motility and morphogenesis using Drosophila and Drosophila derived in tissue culture cells to explore actin, microtubules, and molecular motors. My current lab is composed of fierce, determined undergraduate students. I am a member of the American Society of Cell Biology (ASCB) and the current chair of the LGBTQ+ Committee (https://www.ascb.org/committee/lgbtq/). I am also a member of the Diversity, Equity, and Inclusion Committee for the Genetics Society of America (https://genetics-gsa.org/committees/). I also serve as an editor for MBoC’s Voices series.     

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.     

Finding your unique path in science

I always found it curious that in science, we value unique, creative thinkers, but we teach scientists to progress in a formulaic manner that rarely takes each person’s individual strengths into account. Surprisingly, when we break the mold, we are often rewarded for it. This cycle of learning to survive using conventional wisdom but being rewarded for a unique path outside of it seems to be an unspoken key to success. I am honored to be awarded the 2020 Women in Cell Biology Junior Award for Excellence in Research and am thrilled to share some of the unconventional guiding principles that brought me to where I am in this rich scientific landscape. The game changers in the early phase of my career were informal mentors, open scientific communication, and persistence in pursuing difficult scientific questions.

Prachee Avasthi     

Meet the IUPAB Councilor—Hans-Joachim Galla

As one of the twelve Councilors, it is my pleasure to provide a short biographical sketch for the readers of Biophys. Rev. and for the members of the Biophysical Societies. I have been a member of the council in the former election period. Moreover, I served since decades in the German Biophysical Society (DGfB) as board member, secretary, vice president, and president. I hold a diploma degree in chemistry as well as PhD from the University of Göttingen. The experimental work for both qualifications has been performed at the Max Planck Institute for Biophysical Chemistry in Göttingen under the guidance of Erich Sackmann and the late Herman Träuble. When E. Sackmann moved to the University of Ulm, I joined his group as a research assistant performing my independent research on structure and dynamics of biological and artificial membranes and qualified for the “habilitation” thesis in Biophysical Chemistry. I have spent a research year at Stanford University supported by the Deutsche Forschungsgemeinschaft (DFG) and after coming back to Germany, I was appointed as a Heisenberg Fellow by the DFG and became Professor in Biophysical Chemistry in the Chemistry Department of the University of Darmstadt. Since 1990, I spent my career at the Institute for Biochemistry of the University of Muenster as full Professor and Director of the institute. I have trained numerous undergraduate, 150 graduate, and postdoctoral students from chemistry, physics, and also pharmacy as well as biology resulting in more than 350 published papers including reviews and book articles in excellent collaboration with colleagues from different academic disciplines in our university and also internationally, e.g., as a guest professor at the Chemistry Department of the Chinese Academy of Science in Beijing.

     

Natural Killer Cell Tolerance Persists Despite Significant Reduction of Self MHC Class I on Normal Target Cells in Mice

Background

A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8⁺ T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known.

Methodology/Principal Findings

In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any further effect on the degree of Ly49 downmodulation. Furthermore, a single MHC class I allele could downmodulate up to three Ly49 receptors on individual NK cells. Only when NK cells simultaneously expressed several Ly49 receptors and hemizygous MHC class I levels, a putative threshold for Ly49 downmodulation was reached.

Conclusion

Collectively, our findings suggest that in interactions between NK cells and normal untransformed cells, MHC class I molecules are in most cases expressed in excess compared to what is functionally needed to ensure self tolerance and to induce maximal Ly49 downmodulation. We speculate that the reason for this is to maintain a safety margin for otherwise normal, autologous cells over a range of MHC class I expression levels, in order to ensure robustness in NK cell tolerance.     

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.     

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 Leukocyte Immunoglobulin-Like Receptor Family Member LILRB5 Binds to HLA-Class I Heavy Chains

Objective

The leukocyte immunoglobulin-like receptor (LILR) family includes inhibitory and stimulatory members which bind to classical and non-classical HLA-class I. The ligands for many LILR including LILRB5 have not yet been identified.

Methods

We generated C-terminal eGFP and N-terminal FLAG-tagged fusion constructs for monitoring LILR expression. We screened for LILR binding to HLA-class I by tetramer staining of 293T cells transfected with LILRA1, A4, A5 A6 and LILRB2 and LILRB5. We also studied HLA class I tetramer binding to LILRB5 on peripheral monocyte cells. LILRB5 binding to HLA-class I heavy chains was confirmed by co-immunoprecipitation.

Results

HLA-B27 (B27) free heavy chain (FHC) dimer but not other HLA-class I stained LILRB5-transfected 293T cells. B27 dimer binding to LILRB5 was blocked with the class I heavy chain antibody HC10 and anti-LILRB5 antisera. B27 dimers also bound to LILRB5 on peripheral monocytes. HLA-B7 and B27 heavy chains co-immunoprecipitated with LILRB5 in transduced B and rat basophil RBL cell lines.

Conclusions

Our findings show that class I free heavy chains are ligands for LILRB5. The unique binding specificity of LILRB5 for HLA-class I heavy chains probably results from differences in the D1 and D2 immunoglobulin-like binding domains which are distinct from other LILR which bind to β2m-associated HLA-class I.     

Biophysical Reviews ‘Meet the editor series’—Addmore Shonhai

It gives me great pleasure to have the opportunity to introduce myself to the readers of Biophysical Reviews as part of the ‘meet the editors’ series. What follows is a mini-autobiography of my life as it relates to my scientific career and research.

     

Diversity through equity and inclusion: The responsibility belongs to all of us

Despite the recognized benefits of diversity and the decades of programs targeted at increasing diversity in science, technology, engineering, mathematics, and medicine, the underrepresentation of historically excluded groups continues due to persisting systemic inequalities. It is imperative that we reassess our current recruitment strategies and reimagine our campus and workplace environments to provide an inclusive and equitable culture that is free of institutional barriers, affording equal opportunities for each individual to succeed, thrive, and be their whole self. For too long this vision has been the fight of a heroic few, but it must become the fight of all in order to achieve true change. I am working toward, and look forward to, a future where contributing to diversity, equity, and inclusion is fully integrated into the core mission of our institutions and is an expectation for all of us.

James A. Olzmann

“It is not our differences that divide us. It is our inability to recognize, accept, and celebrate those differences.” —Audre Lorde

I am honored and grateful to receive the Günter Blobel Early Career Award from the American Society for Cell Biology (ASCB). As a graduate student, I was fortunate enough to receive a travel award through the ASCB Minorities Affairs Committee that allowed me to attend the 2005 ASCB annual meeting. I recall my first meeting as both a daunting and exhilarating experience, and I excitedly attended talks from my science heroes. Over the years, the excitement of the annual meeting has never faded for me, and it now feels much like a reunion of friends and colleagues. I have also come to appreciate that ASCB is much more than just the annual meeting—it is a community of amazing cell biologists and it is our community! Everything has come full circle and I am privileged to be a member of the ASCB Minorities Affairs Committee, striving to pay it forward to students from diverse backgrounds and to cultivate an inclusive community where we all feel that we belong and are welcomed.During a typical year, I would take this opportunity to discuss my path to become a cell biologist and how I became fascinated by lipid droplets, offer some tips for success in science and research, and perhaps wax poetic about the power of collaboration and mentorship. However, I think we can all agree that 2020 is not a typical year. Our world continues to reel from the impact of the COVID-19 pandemic and we are in the midst of the Black Lives Matter movement, the fire for this an anti-racism revolution rekindled by the needless and heartbreaking deaths of George Floyd, Breonna Taylor, and so many others. These events, which are just the most recent examples of all too common racially motivated violence, shine a light on our reality born out of a legacy of racism that permeates all aspects of our society. It is an understatement to say that our scientific community is not exempt from these systemic injustices, biases, and inequalities. To gain some small insight into the scope of the problem, we only need to look towards the #blackintheivory and #blackinivory hashtags on Twitter and recently published stories (Simmons, 2020) that chronicle the lived experiences of our black colleagues—the microaggressions, implicit and explicit bias, tokenism, etc. It is with these current events as the backdrop that I focus this essay on the need for systemic change and the importance of achieving diversity through equity and inclusion in science, technology, engineering, mathematics, and medicine (STEMM).     

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.