Being at the right place at the right time

I am tremendously honored to receive the 2012 Women in Cell Biology Junior Award. In this essay, I recount my career path over the past 15 years. Although many details are specific to my own experiences, I hope that some generalizations can be made to encourage more women to pursue independent scientific careers. Mine is a story of choosing a captivating question, making the most of your opportunities, and finding a balance with life outside the lab.It is a great honor to have been awarded the 2012 Women in Cell Biology Junior Award from the ASCB. Looking back at the 15 years I have spent doing research in cell biology, my overwhelming feeling is that it has been and still is a lot of fun. I am extremely fortunate to have a job that I truly enjoy and that gives me complete intellectual freedom. My lab choices over the years were motivated by scientific curiosity and enthusiasm for new environments and topics, rather than by career building. It is thus truly amazing to be rewarded for (rather a lot of) work enjoyed.     

Stems and Standards: Social Interaction in the Search for Blood Stem Cells

This essay examines the role of social interactions in the search for blood stem cells, in a recent episode of biomedical research. Linked to mid-20th century cell biology, genetics and radiation research, the search for blood stem cells coalesced in the 1960s and took a developmental turn in the late 1980s, with significant ramifications for immunology, stem cell and cancer biology. Like much contemporary biomedical research, this line of inquiry exhibits a complex social structure and includes several prominent scientific successes, recognized as such by participating researchers. I use personal interviews and the published record to trace the social interactions crucial for scientific success in this episode. All recognized successes in this episode have two aspects: improved models of blood cell development, and new interfaces with other lines of research. The narrative of the search for blood stem cells thus yields a robust account of scientific success in practice, which generalizes to other scientific episodes and lends itself to expansion to include wider social contexts.     

Adventures in Neural Plasticity, Aging, and Neurodegenerative Disorders Aboard the CWC Beagle

This article recounts some of the scientific endeavors of Carl W. Cotman (CWC) during his journeys through the cellular circuitry of the mammalian brain. I have selected for consideration his findings that have been an important impetus for my own research; in several cases our different experiments have provided complementary data to support an hypothesis. Three examples are (i) Carl's studies of the roles of glutamate in synaptic transmission and plasticity in the adult brain and my studies of how glutamate regulates neurite outgrowth and cell survival in brain development; (ii) his and our studies of the mechanisms whereby amyloid -peptide damages and kills neurons; and (iii) Carl's evidence that physical activity regulates neurotrophin levels in the brain and our evidence that dietary restriction has similar effects and is neuroprotective. In case you have not yet realized how I chose a title for this article it is because Carl has a (very distant) connection with Charles Darwin—Darwin sailed on a vessel called the Beagle and Carl has studied beagle dogs, establishing them as a model for understanding the neurobiology of human brain aging.     

A path to the powerhouse: systems‐to‐structure approaches for studying mitochondrial proteins

The young investigator award from the Protein Society was a special honor for me because, at its essence, the goal of my laboratory is to define what obscure proteins do. Years ago, I stumbled into mitochondria as a venue for this work, and these organelles continue to define the biological theme of my laboratory. Our approaches are fairly broad, reflecting my own somewhat unorthodox training among diverse scientific fields spanning organic synthesis, chemical biology, mechanistic biochemistry, signal transduction, and systems biology. Yet, whatever the theme or the discipline, we aim to understand how proteins work—especially those that hide in the dark corners of mitochondria. Below, I recount my own path into this arena of protein science, and describe how my experiences along the way have shaped our current multi‐disciplinary efforts to define the inner workings of this complex biological system.     

The Chemical Synthesis of DNA/RNA: Our Gift to Science

It is a great privilege to contribute to the Reflections essays. In my particular case, this essay has allowed me to weave some of my major scientific contributions into a tapestry held together by what I have learned from three colleagues (Robert Letsinger, Gobind Khorana, and George Rathmann) who molded my career at every important junction. To these individuals, I remain eternally grateful, as they always led by example and showed many of us how to break new ground in both science and biotechnology. Relative to my scientific career, I have focused primarily on two related areas. The first is methodologies we developed for chemically synthesizing DNA and RNA. Synthetic DNA and RNA continue to be an essential research tool for biologists, biochemists, and molecular biologists. The second is developing new approaches for solving important biological problems using synthetic DNA, RNA, and their analogs.     

Engaging the Sociological Imagination: My Journey into Design Research and Public Sociology

I chronicle the changes in my research, especially those that have moved me closer to C. Wright Mills's call for a "sociological imagination" and Dell Hymes's reinvented anthropology. As I spend more time attempting to create and describe equitable educational environments and less time documenting educational inequality, I have adopted a version of "design research." I describe the possibilities and limitations of trying to conduct research while participating in the phenomenon under investigation.  [sociological imagination, critical ethnography, public sociology, design research]     

Radicals in Berkeley?

In a previous autobiographical sketch for DNA Repair (Linn, S. (2012) Life in the serendipitous lane: excitement and gratification in studying DNA repair. DNA Repair 11, 595–605), I wrote about my involvement in research on mechanisms of DNA repair. In this Reflections, I look back at how I became interested in free radical chemistry and biology and outline some of our bizarre (at the time) observations. Of course, these studies could never have succeeded without the exceptional aid of my mentors: my teachers; the undergraduate and graduate students, postdoctoral fellows, and senior lab visitors in my laboratory; and my faculty and staff colleagues here at Berkeley. I am so indebted to each and every one of these individuals for their efforts to overcome my ignorance and set me on the straight and narrow path to success in research. I regret that I cannot mention and thank each of these mentors individually.     

Scientific Apps are here (and more will be coming)

The world of Apps is now well upon us although the application of this tool was a bit slow in coming to the scientific community. In this column I will briefly take a look at some of the Apps now available that are applicable to biomedical research. I will restrict my coverage to the Apple format, not because I am totally an Apple user (my PC is a Dell) but only because I do not have an Android device.     

花部特征演化的最有效传粉者原则:证据与疑问

自然界千姿百态的花是如何演化而来?前人曾提出花部特征是由当地最频繁的、最有效的传粉者所塑造的观点,但是吸引传粉者的特征也可能吸引植物的敌人——植食动物。花的特征与其他特征一样也经受着环境因子的选择作用。论述了支持花部特征演化的最有效传粉者原则的证据,该原则受到质疑的论点;再从植食作用、环境、传粉后的选择等方面,就花部特征选择的生态因子,列举了一些前人和作者提出的证据,以及需要深入研究的问题。     

Melanocyte development: with a message of encouragement to young women scientists

This is a semi-biographical review describing my research on melanocyte development and related personal experiences. Having been educated and trained as a dermatologist, I have been involved in many clinically-oriented studies, however, what has always interested me the most is pigment cell biology. Since I started working at St Marianna University in 1991, I have been undertaking research on melanocyte development and relevant growth factors using mice as models. My research in this field was inspired by my collaborations with various scientists, mostly from the field of biology. Many of these specialists I have met at meetings of the Societies of Pigment Cell Research (PCR). Stem cell factor (SCF, Kitl) and endothelin 3 (EDN3) have been identified as indispensable factors regulating the development of melanocytes. Mice mutant at loci encoding those factors (or their receptors) such as Sl/Sl (receptors W/W) and ls/ls (receptors s/s) have white coat colors and white patches, respectively. Our murine neural crest cell (NCC) primary cultures derived from Sl/Sl embryos showed that EDN3 cannot develop melanocyte precursors without SCF and that EDN3 can elicit proliferation and differentiation in the presence of SCF. These results suggest that without EDN3 and the endothelin type B receptor (EDNRB), melanocytes can not fully increase in number, which could well be the cause of the partial white coat color of ls/ls and s/s mice. Contamination with factors derived from the serum in medium or in feeder cells sometimes causes experimental errors, and therefore we established three immortal cell lines derived from NCC in different developmental stages and designated them as NCCmelb4, NCCmelb4M5 and NCCmelan5, all of which can survive without feeder cells. Using these cell lines and NCC primary cultures, we studied the effect of many factors related to melanocyte development. From the results, it has become evident that Vitamin D3 induces EDNRB expression by NCCmelb4 cells. In addition to the International Pigment Cell Conference (IPCC), I have also taken part in many annual meetings of the Japanese Society for Pigment Cell Research (JSPCR), Pan American Society for Pigment Cell Research (PASPCR) and European Society for Pigment Cell Research (ESPCR). Not only have I learned a great deal, I have enjoyed myself immensely at those meetings. Moreover, I have made many good friends there, some of whom I have collaborated with in my research. To conclude, I would like to give my message 'be ambitious' to young scientists, especially young women.     

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

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

Balancing teaching and research experiences in doctoral training programs: lessons for the future educator

While a variety of alternative careers has emerged for Ph.D. life scientists in industry, business, law, and education in the past two decades, the structure of doctoral training programs in many cases does not provide the flexibility necessary to pursue career experiences not directly related to a research emphasis. Here I describe my efforts to supplement my traditional doctoral research training with independent teaching experiences that have allowed me to prepare myself for a career that combines both into a combined educational program. I describe the issues I have come across in finding and taking part in these endeavors, how these issues have affected my work in pursuing my Ph.D., and how my experiences translate into my hopes for a future education-based career in molecular and cell biology.     

Teaming up: from motors to people

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

Experiments

In this article, I have provided a brief history of my life. After tracing my family background and my early interest in physical sciences, I discuss how I entered biology under the influence of Robert Emerson. I have always enjoyed doing experiments and this led to new measurements and analyses of chlorophyll unit, efficiency of photosynthesis, excitation energy transfer, delayed light emission, thermoluminescence and electroluminescence in photosynthetic organisms. It is my view that discoveries are made because we follow our scientific curiosities.This article was written at the invitation of Govindjee.     

The sociobiology of ethnocentrism in an Indian City

In this article, I examine whether inter- and/or intraunit variation in ethnocentrism— a trait not automatically connected with mortality/natality rates—can be correlated with differential reproductive success. As a preliminary test of general theoretical models in the literature regarding the sociobiology of ethnocentrism, it was postulated that the more ethnocentric an ethnic unit is, the more important ethnocentrism is for the members of that unit. With the use of this postulate, hypotheses were generated and tested with empirical data obtained through field research among two ethnic units—Tamils and Gujaratis—in the city of Pune, India. It was concluded that: 1) if interunit aggression and kin selection were predominant characteristics of the early hominid environments of evolutionary adaptation, then from a sociobiological perspective, ethnocentrism can be explained as an evolved human trait, intimately linked to kin selection and interunit warfare; and, 2) under what I assumed to be novel environmental conditions ethnocentrism and reproductive success appear to be uncorrelated; and, 3) because the possibility exists that novel environmental contengencies were acting to level off reproductive variance upon which natural selection could have operated in my sample, only future research in a society similar in structure to those we tend to identify with early hominid environments of evolutionary adaptation will allow researchers to rule out the possibility that ethnocentrism is an evolved human “biocultural” trait.     

Lessons learned from Art Pardee in cell cycle, science, and life

This essay is written to honor Dr Art Pardee's 85th birthday (July 13, 2006). In this essay, I have summarized the lessons I learned from Art and the cell-cycle research I performed in Art's laboratory during my postdoctoral training period. I have also summarized some research from my own laboratory that has been inspired by the lessons I learned from Art, including the interactions between cell cycle and cell death regulators and discovery of novel polyphenol- and copper-based proteasome inhibitors. Finally, I have discussed the potential use of these proteasome inhibitors in cancer prevention and treatment.     

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.