Passion and Diligence: a Silver Bullet to Reach the Top?

Newsletter No. 10

December 2018 — National Center of Competence in Research, RNA & Disease

Success stories of three NCCR RNA & Disease professors Passion and diligence: A silver bullet

to reach the top? Dear colleagues Interview: Larissa Grolimund and Ana Claudia Marques

For most of us, being a scientist is more than Three NCCR RNA & Disease professors What is the main research question a job, it’s part of our identity. In this edition at different career stages give deep in your lab? of the Messenger, three NCCR RNA & Dis- and personal insights into their career We study mechanisms of RNA process- ease Professors share personal insights into paths by talking about opportunities, ing and RNP assembly in human cells and their academic journey and the challenges difficulties and obstacles they encoun- work towards a better understanding on and opportunities that shaped their careers. tered along the way. Stefanie Jonas, how errors in these processes can lead to My take-home message from these inspiring Magdalini Polymenidou and Frédéric diseases. accounts is that “where there is a will, there Allain share with us their view on is a way” and that there are different ways to mentoring, gendered science programs When and why did you choose succeed as a scientist in academia. Retaining and how to juggle a career in science to become a scientist? and fostering this diversity is central to the with having a family. Their experiences Looking back, it was not a decision that I Equal Opportunities strategy of the NCCR in and pieces of advice are diverse and could pinpoint, but rather a slowly grow- RNA & Disease. However, we still fall short on tailored for the individual situations ing determination. My fascination with the number of women in academic leader- they encountered as young researchers natural sciences started early in child- ship roles in the NCCR. In an article of this embarking on a career in science. But hood, I always wanted to understand on a Newsletter, I describe how unconscious or a common theme of the stories of Ste- fundamental level, how the world around implicit bias are one of many factors contrib- fanie Jonas, Magdalini Polymenidou us works. In high school, I carried out my uting to the lack of gender diversity in leading and Frédéric Allain is also that there first smaller research projects. That was the academic positions, and what we can do to is not one single road to success, al- point at which I decided to study chemis- minimize the impact of biased decisions on though passion for and dedication to try, because I was curious and wanted to gender diversity. As a relatively small organ- science in combination with appropri- learn more about the molecular principles ization, we have the privilege to implement ate training and support remain the that govern nature. My inclination towards innovative measures. With the aim of min- critical ingredients that lead you to practical research deepened during my imizing the penalty of maternity on female the top. undergraduate and graduate studies and trainees’ career, we recently implemented the from my Master's thesis on, I poured all pregnancy and maternity leave compensation my energy into basic research. scheme. We report on the short-term impact and experiences of this scheme for the first How did you get to the position you are cohort of grantees. Finally, we share some in today? Can you give us a short descrip- of the insights we gained at an international tion of your career? meeting on Equality in Amsterdam. We will Biomolecular chemistry became my fo- continue to develop the NCCR RNA & Disease cus towards the end of studying classical Equal Opportunities strategy during Phase 2 chemistry in Göttingen. Because there and hope that the novel and existing measures were not many opportunities to go deep- will contribute to an increase in diversity at all er into biochemistry in my department, I career stages and will facil- went abroad for the research project of itate the journeys of NCCR my Master's thesis. With a Studienstiftung scientists. scholarship, I joined Jennifer Doudna's lab at UC Berkeley. This was my first in-depth Ana Claudia Marques contact with molecular biology and RNA Equal Opportunities Delegate Stefanie Jonas is an Assistant Professor at the and Principal Investigator Institute of Molecular Biology and Biophysics at research. About one year later, after com- NCCR RNA & Disease ETH Zürich, Switzerland, since 2017. pletion of my thesis, I moved on for a PhD THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 2

Success stories of three NCCR RNA & Disease professors

in Florian Hollfelder's group at the University During my post-doc at ETH, I became a How do you handle the high demand of Cambridge. There I studied how enzymes member of a peer-mentoring group. It was for mobility in your career with having can efficiently catalyze chemically diverse actually initiated by two post-docs as part of a family? reactions and how this feature is exploited the NCCR's [NCCR Structural Biology, editor’s In the past, my husband and I both pursued by nature during evolution of new enzyme note] equal opportunities program. It is still our education and specialization at the insti- functions. For my postdoc, I went back into running and consists of an informal group of tutions that promised the best progress for the RNA world. In Elisa Izaurralde's lab at the female PhD students, post-docs and senior our vocation. This also meant that we spent Max-Planck Institute in Tübingen, I studied scientists that meet monthly for discussions a number of years apart, living in different nonsense-mediated mRNA decay and general over lunch. We provide support and advice countries, including the U.K. and the U.S. mRNA degradation complexes. Before start- for each other in terms of career and scientif- Currently, we live together as a family in Zu- ing my own group, I joined Ulrike Kutay's lab ic progress. The meetings had a very encour- rich. at ETH Zurich to start working on RNP as- aging effect on me, and the group was one sembly during a second, short post-doctoral of the factors that contributed towards me Based on your professional experience so research period. taking the next steps and applying for group far and if you had one advise you could give leader positions. One great thing about such your younger self what would this be? Did you ever consider leaving academia and an informal group is that it could be founded Take heart, there is good reason to maintain if so what made you stay? by any student or researcher anywhere. Time hope and keep working towards your goals. Leaving academia has so far not appealed commitment is minimal, but nonetheless in Do not let go of your dreams. to me as a goal, I have always been looking our group the effects of this peer-mentoring for options to keep on doing basic, academic have been beneficial for all its members. research. In your opinion do women in science need Did you/do you have mentors during your gender-specific events/awards? Why? career? How crucial do you think is mentor In some areas that might be approached dif- ship for the professional development in ferently by women and men, I have made academia? Do you think mentorship for good experiences with gender-specific work- female scientists should differ from that for shops that addressed e.g. negotiation tools, male scientists? communication, or how to use one's voice So far, I have not seen substantial differences efficiently. in mentorship for female or male scientists. However, what is also significant is the effect of role models. They are very important, “Flexibility from all per- because they provide a backdrop of normal- cy and templates for how "someone-more- sons and institutions like-me" can succeed in this job. By chance, four of the five supervisors and PIs that I involved has also been Magdalini Polymenidou is an SNSF Assistant Professor since 2013 with a double appointment have worked with were women, every one of between the Faculty of Science and the Medical them successfully mastering the challenges key. ” Faculty of the University of Zurich, Switzerland. of a scientific career in their own way. I am grateful to all my previous PIs for What is the main research question having granted me the freedom to drive proj- What is your experience of balancing career in your lab? ects into the directions that I wanted to pur- and family and what are the challenges and We investigate the molecular pathways that sue. Furthermore, they have supported me in benefits of “having it all”? lead to the neurodegenerative diseases amy- the next steps with advice, encouragement, My experience in this is only one year old. otrophic lateral sclerosis and frontotemporal practical help and with recommendations, So far I can say that it is crucial to bring in dementia. Key players in the pathogenesis of whenever I applied for fellowships or sub- all the support that one can get to organize these diseases are the RNA-binding proteins sequent positions. This type of support net- childcare: from one's spouse, family, daycare TDP-43 and FUS, so our research intersects work, I would argue, is essential for everyone institutions, or hired help. For us, the Kitas at with basic RNA and phase separation biolo- who wants to build a career in academia. ETH have proven to be very valuable and flex- gy, which are particularly exciting and active ible programs such as "Kita Flex" have made research fields. Specifically, our lab aims to 1) it possible to return quickly to a sustainable understand the toxic mechanisms and the ba- “This type of support working mode and to adapt to changes in sis of disease heterogeneity, 2) devise faithful professional schedules. My husband and my cellular and animal models of disease and 3) network, I would argue, brother are also of great help, each contrib- eventually identify new molecular targets for uting one day of child-care a week, which mechanism-based therapies for these diseas- is essential for everyone allows me to work full time. Flexibility from es, which today are incurable and fatal. who wants to build a all persons and institutions involved has also been key. Thankfully, my team (and also our When and why did you choose career in academia.” baby) are understanding of the slightly un- to become a scientist? usual circumstances and are very supportive. I took the decision very early on, I guess in In summary, for both my husband and I, my childhood, even if I didn’t exactly know What programs or events to which you having a family and a challenging profes- what it meant then. As a child I was influ- have participated do you think have been sion have proven a great joy, and we are im- enced by my father, who was a medical doc- most useful for your career progression? mensely grateful. tor and my uncle, who was an engineer and THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 3

Success stories of three NCCR RNA & Disease professors

an academic scientist. Both had successful encouraged me to search for a PhD posi- Have you actually ever thought about your- careers and were passionate about science tion in a leading academic institution. This self as a “woman in science” as compared and they have passed this passion on to me has brought me to the University of Zurich to “just” a scientist? If so, was this the case from a very young age. I remember stating and the laboratory of Adriano Aguzzi, where right from the start of your scientific career that I will do a PhD before I could write, I studied prion biology and disease mecha- or did it come up later? which made my grandparents laugh. Already nisms. Coming from Greece, where funding Not in my early years. As a child and teen- then I was convinced that research was the and infrastructure was minimal, research in ager, I never thought of this. My family’s most exciting “job” one could do. And now, the Aguzzi lab was full of possibilities. This “normal” was a working mother who, al- a few decades later, I am happy to say that time has shaped me as a scientist and taught though she chose a less demanding career this conviction hasn’t changed! me to combine focus with creativity in my than that of my father, never questioned research. This was a particularly productive gender equality in terms of career ambitions. period that set up the foundation for an aca- My mother herself studied gender bias as a demic career. In fact, I enjoyed working there part of her master’s degree and I remember so much that it was hard to leave. After I conversations at the family table on this top- “Already then I was con- defended my thesis in early 2006, I stayed in ic since I was a child. Both my parents have vinced that research the lab as a postdoctoral fellow for almost raised my older brother and myself without two years. During this time, I have worked any such biases, at least when it comes to was the most exciting for six months with a Novartis team in Cali- our professional development. The aim was fornia on a prion diagnosis project. This gave the same for us both: “find something you ‘job’ one could do.” me a unique perspective and appreciation of love and do it as best as you can”. I also had the industry world that most academic sci- very dedicated and knowledgeable teachers entists don’t experience. After that, in early in high school who instilled the importance 2008, I moved on to my postdoctoral studies of gender equality. Surprisingly, the first time How did you get to the position you are in to the lab of Don Cleveland at the University I realized that other people might see things today? Can you give us a short description of California in San Diego. I chose this lab of your career? because I wanted to work on a different field Many turning points in my career path have of neurodegeneration and to focus on a fun- been serendipitous and I think that this is damental, mechanistic question and to ex- “It takes a lot of per- probably true for most people. At the last pand my scientific horizons. I was extremely years of high school in Greece – which would lucky to enter the field of amyotrophic lateral sistence and focus be the equivalent of the Gymnasium in Swit- sclerosis (ALS) at a particularly exciting time, zerland – I had decided that I wanted to do when a number of breakthrough discoveries and it is not always research on disease mechanisms. For this pointed to alterations of RNA-processing as reason, I was intending to study medicine, a (then) novel mechanism for ALS pathogen- easy, but it is definitely which I thought would give me the best basis esis. Indeed, identification of ALS-causing worth it!” for this. However, in the Greek education- mutations in two new genes encoding for al system, entering Medical School – or any RNA-binding proteins – namely TDP-43 and other University level or professional school FUS/TLS – were reported by several groups – depends on a single nation-wide exam that worldwide, soon before and during my differently was in Switzerland, when after I ranks students based on their performance postdoctoral studies at UCSD. These devel- defended my thesis I was discussing with a and then distributes them to Schools, accord- opments provided a unique opportunity for more senior male lab member about post- ing to their own preference list. To cut a long my postdoctoral work, which allowed me to doctoral opportunities abroad. I was shocked story short, I did not get my first preference, become an “incidental” RNA biologist, as I when he asked me why bother, since I will but my second one, which was Pharmacy, so chose to investigate how alterations in these soon have a family anyway. The most shock- you can say that my career started with a two proteins may affect RNA processing and ing part of his reaction for me was that it was failure. Studying Pharmacy at the Aristotle thereby trigger neurodegeneration. This time honest – he didn’t mean to offend me, he University of Thessaloniki, however, turned also prepared me well for academic indepen- was genuinely perplexed – and that it came out to be just as good a starting point, if dence and my next career step, which was from a person that I respected as a colleague not better. During the last two years of my the setup of my own research group as an and a scientist. studies, I joined the lab of Theodoros Skla- Assistant Professor at the University of Zurich viadis, who was our Pharmacology Professor in September 2013. Did you ever consider leaving academia and and who had just returned to Greece from if so what made you stay? Yale Medical School to set up a research lab I have had some disheartening moments in to study prion diseases. This at the time was my career and on these moments I wondered a very active research topic due to the mad if life would be easier had I chosen a different cow disease epidemic in Europe, so many “I was shocked when he path. These were short-lived, however, and I excellent laboratories throughout Europe soon saw that difficulties and failures are part were focusing on it, often collaborating via asked me why bother, of any career – not just in academia. It is this European funding. Prof. Sklaviadis was my since I will soon have a realization that made me stay the course and first scientific mentor and has been extreme- I sometimes tell my students that the most ly supportive to me and to all the students family anyway.” difficult part in scientific research is to deal that have passed by his lab over the years. with frustration. It takes a lot of persistence He has instilled the belief that mobility is and focus and it is not always easy, but it is essential for evolving as a scientist and has definitely worth it! THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 4

Success stories of three NCCR RNA & Disease professors

Did you/do you have mentors during your CSHL or other organizations, which were in- this career and equally shares childcare and career? How crucial do you think is men- tense and short – ranging from a few days to family time with me. torship for the professional development a few weeks depending on the topic – and For me, I guess the biggest challenge is in academia? Do you think mentorship for focusing on a specific technique or scientif- time. Sometimes, it feels like there are not female scientists should differ from that for ic topic. These were fantastic for immersing enough hours in a day and it is this feeling of male scientists? the participants into a new topic and to in- “inadequacy” that I find the hardest. I think I have had wonderful and influential mentors troduce them to other scientists with similar it is great that organizations like EMBO, ERC, in my career and I consider myself very lucky interests from all over the world. A special SNF, HFSP, NIH and several others appreciate for this. I think good mentorship is absolute- course in such a setting was the EMBO Lab this natural “imbalance” and apply measures ly crucial for a successful scientific career. I management course, which I took as an early to counteract it. I find this particularly mo- think that mentorship needs to be adjusted postdoc and which helped me think about tivating and I think that everybody benefits to the personality and peculiarities of each important aspects for taking the steps to- from making it equally possible for women individual and career path. Gender is a factor wards an independent scientific career. to successfully combine family and career. For of this, but certainly not the only one and I me personally this combination means happi- don’t think that there is a single recipe that In your opinion do women in science need works for everyone in this case. It certainly gender-specific events/awards? Why? helps to talk with someone that understands This is a difficult question and I can think of the specific demands and dilemmas of your good reasons both for and against the idea. “Sometimes, it feels like own life and that can give you some real-life On the one hand, if gender equality is the examples of how to deal with them. For me goal – which in my opinion it is – then we there are not enough a very important aspect was that my men- shouldn’t need any gender-specific measures tors, who I deeply admire for their scientific at all. In reality, however, while we are far hours in a day and achievements and vision, believed in my own from an ideal gender-balanced scientific abilities and potential as a scientist. This has world, I think that we do need to highlight, it is this feeling of boosted my confidence and helped me over- support and celebrate women scientists. This ‘inadequacy’ that I find come my own “impostor syndrome” that I is important in order to boost the careers of think is characteristic for many women sci- talented women, but also to inspire girls and the hardest.” entists. young women that are inclined towards a scientific career, but may hesitate due to so- Do you think that specific programs or cietal stereotypes that are unfortunately very events that you have participated in have persistent. In my opinion, one of the biggest ness! I could not imagine my life without the been particularly useful for your career obstacles for the younger generations is that satisfaction from my research and from work- progression? examples of successful women scientists are ing with many talented students, postdocs Especially in the beginning of my career, at- much fewer than that of men, especially in and collaborators. But I also cannot imagine tending international scientific meetings has Europe and even more so in Switzerland. a life without my children and the joy from played a very important role, because they Putting women scientists to the spotlight in seeing them grow and discover the world. were the inspiration that made me appreci- a positive manner is one way to counteract Ideally, nobody should feel like they have to ate the life of a researcher. I remember how this trend. choose between these two. And we should fascinated I was, when, as an undergraduate strive to make this possible. student, I attended such a meeting on prion What is your experience of balancing career diseases in Germany. At the time it felt like and family and what are the challenges and How do you handle the high demand an entire new world was appearing in front benefits of “having it all”? for mobility in your career with having of me, one with likeminded people that were I think that it is hard to balance family and a family? curious and passionate about making scien- career for everybody, both women and men. This is an important point that seems to dis- tific discoveries. Later, during my PhD and My younger self was often annoyed by the courage many young scientists from pursuing postdoc years, I have attended a number of fact that the “having it all question” is only a scientific career. For me, having to move courses and workshops, organized by EMBO, – or mostly – asked to women. Men have for my PhD (from Greece to Switzerland) and always been “having it all” and no-one postdoc (from Switzerland to the USA) were seems to question their abilities in this re- both exciting prospects that I took as life ad- spect. However, since I have my own family, ventures rather than burdens. The fact that “While we are far I have come to realize that it is important to my husband is also a scientist helped, since recognize the fact that having children takes moving was eventually advantageous for from an ideal gender- a much bigger toll on a woman’s life, par- both careers, as is often the case for scientist ticularly during pregnancy and nursing, and couples. Once we had children, however, cre- balanced scientific that fact is independent from societal ste- ating a stable environment for them became reotypes. During this period, no matter how a priority. Our next move (from the United world, I think that we involved a father may choose to be in family States to Switzerland) was when my first son do need to highlight, life, women face a decrease in productivity, was one year old and even though we were almost invariably. This can be a short period, returning to a more familiar environment, support and celebrate however, and soon after, family-career bal- moving was much harder than before. I think ance is a matter that should concern both that mobility is rightfully valued in an aca- women scientists.” genders equally. I am lucky that this is the demic CV since it offers so much in terms of case in my own family. My husband, who is training, experience and way of thinking. In also a scientist, understands the demands of my opinion, however, it is important to view THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 5

Success stories of three NCCR RNA & Disease professors

each case individually and not make mobili- (ENS). In that school, the goal is primarily to a postdoc in a neighboring lab. I do men- ty a hard requirement or eligibility criterion, train teachers and researchers; so the goal tion these personal issues to emphasize the since this disproportionally drives women was set, but the path needed to be created. difficulty of mixing the academic track with away from academia. personal relationships. I should say that in the How did you get to the position you are in end, it did not work out better, as we never Based on your professional experience so today? Can you give us a short description got back together as before, and we broke far and if you had one advice you could of your career? up a second time 7 months after starting our give your younger self what would this be? This was realized step by step and not with postdocs. Now, there were some advantag- Worry less, trust yourself more and don’t for- this objective as a long-term goal. In research, es in what happened to me with these two get to celebrate each step and to enjoy the I do not think that you can plan a career. I “breakups”, as they resulted, in both cases, journey! remember this discussion with an American with me working twice as much. Being single PhD student during my PhD studies, who told and living in a foreign country allowed me to me that his plan was to become a professor focus and concentrate fully on my work. It in one of the top five US University within was also a great motivation to succeed in sci- 10 years. He then enquired about my plans, ence, as I was quite unfortunate with my per- and I remember telling him that I had none sonal life. In the end, the postdoc was also beside graduating and publishing at least one successful and I therefore quite naturally ap- paper. This was true, but he did not believe plied to faculty jobs in the US and in Europe. me! This was in 1993 and I was appointed as It did not work out the first year, and this is an assistant professor at ETH in 2001. So, to the reason why I decided to go for a second some extent, I achieved without planning it postdoc in the lab of Prof. Doug Black. There, what this American student was dreaming of. I wanted to learn something different, i.e. al- His own PhD was not as successful as he was ternative splicing in neurons, as my PhD and hoping for, and he never fulfilled the goal he postdoc labs were both in the field of NMR had set out for himself. of nucleic acids. Faculty job searches worked So, to come back to the question, after out better in the second year of applying, studying chemistry at the ENS and doing a and I got several offers (two were tenured master in bioinorganic chemistry, I got the positions and one tenure-track from ETH). I Frédéric Allain is Full Professor at the Institute of opportunity to visit the MRC-LMB in Cam- went for the more risky one and joined the Molecular Biology and Biophysics at ETH Zürich, bridge (UK) during a visit to my father in ETH Zurich as an assistant professor in 2001. Switzerland since 2010 and Co-director of the NCCR RNA & Disease since 2014. Cambridge. My father, who is a professor in I got tenured in 2007 and have been a full Hematology, had arranged for me to meet professor since 2010. I met my wife in 2001, What is the main research question the Director of Studies of the LMB. At the in the first months of my arrival in Switzer- in your lab? time I had no idea about this lab, but after land, and we have been living together since In my lab, we are interested in how RNA visiting it and meeting with two PIs, I was 2002. We have a daughter who was born in binding proteins (RBPs) regulate gene ex- fascinated. I discovered a world-class lab 2010, when I was 40 years old. pression post-transcriptionally. We take a and was very keen to join it! My luck was structural biology approach to understand two-fold; financial support from the ENS for this. We solve structures of protein-RNA com- two years on the one hand, and on the oth- plexes to understand the role and mechanism er hand, the need for military reason to be “I must say that I was of action of RBPs in regulating splicing, RNA studying abroad for 16 months under the editing, miRNA processing and translation. condition that the lab would pay my salary. not very keen to have During the interview, I met my future PhD When and why did you choose to become adviser, Dr. Gabriele Varani, who impressed a female PI as PhD a scientist? me greatly with his enthusiasm. Although I This was quite late in my studies. I always had no guarantee that they would pay the advisor. This shows liked science but not more than politics, 16 months, I still decided to join MRC-LMB in anthropology, history and psychology. My the Varani lab for my PhD. At that time, I also that back in 1993 I had grandfather, who was an archeologist made the hard personal decision of going to (pre-history and gallo-roman period), was the UK despite the fact that my girlfriend was a ‘stupid’ prejudice certainly an inspiration to become a research- staying in France to pursue her PhD. This was against women in er; I did learn a lot from him. The excitement a very difficult decision to make, and the re- for biology came from studying biology at lationship did not survive past the first year science.” high school and then in “classe prépara- of my PhD studies. Despite the fact that I toire” where I had a really fascinating Biology really enjoyed my PhD at the LMB and pub- teacher (Mr. Darchy). He was clearly doing lished nine papers, which gave me a great more than the usual classes, organizing field start in the academic world, I did feel guilty Have you actually ever thought about your- trips etc. and was very encouraging to me. about this personal decision. To the point self as a “man in science” as compared to He really transmitted a passion for biology that, three years later, I asked my “ex-girl- “just” a scientist? If so, was it like this from and made us realize that there is a lot to dis- friend” if she would join me for a postdoc the start of your scientific career, or did it cover in this field. This mentality motivated in the US. We then searched together and come up later? me to study hard and it certainly was an asset the choice of joining the lab of Prof. Juli Fei- Yes, of course. From the very beginning. I re- in my later succeeding in entering the pres- gon at UCLA was partly motivated by the member that when I heard I would meet with tigious “Ecole Normale Supérieure” in Paris fact that Juli helped my “ex-girlfriend” find Gabriele Varani (Gab), I thought Gabriele was THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 6

Success stories of three NCCR RNA & Disease professors

a female PI, since “Gabrielle” in French is a tive (my grandfather, Darchy or Gab), while not so simple. As mentioned above, my rath- female first name. I must say that I was not others might show you a path that you er unsuccessful personal life at the beginning very keen to have a female PI as PhD advi- should not follow (Juli at times). Feeling that of my scientific career turned up to be rather sor. This shows that back in 1993 I had a your mentor “believes” in you is very import- positive. My research project was the only “stupid” prejudice against women in science. ant, but you will not go very far if in the first positive aspect of my life at that time and this The lab I was working in at the time in Paris place you do not believe in yourself. It is in- was almost a question of survival. Science is a during my master in bioinorganic chemistry teresting to see that in fact both aspects are creative process and suffering certainly favors was dominated by male professors and had rarely present simultaneously, me believing in creativity. Research in science is fascinating very few female scientists in the lead. Yet, all them and them in themselves as well. but is not made for people aiming at com- the PhD students were female. Anyway, I did fort. This is part of the dilemma we are facing accept the interview and found out that Ga- What programs or events to which you have between career and family. We seek comfort briele was a man. However, when looking for participated do you think have been most and stability to raise our children, but our a postdoc, I did not hesitate to apply to Juli useful for your career progression? work requires creativity that can often only Feigon, a female professor at UCLA. I must There are several. The first thing is meeting be triggered by stress and instability. In con- admit that the fact she was a female scientist the right people, as discussed above. Attend- clusion, it is hard to “have it all”. was an element of my decision, along with ing meetings where you can orally present the attraction of working in a great scientif- when you are a PhD student or a postdoc How do you handle the high demand ic environment. I was certainly keen to find has been really important to me, as these for mobility in your career with having out if there would be a difference in man- meetings were a great motivation to work a family? agement compared to what I experienced hard and collect enough material to compete Again, I come back to my story during the during my PhD and Master. This was indeed with others and be selected for an oral pre- PhD and the postdoc. I already moved during a very different management. I think that, at sentation. In that context, the RNA society my PhD studies and the consequence was an times, I was emotionally closer to Juli than to impaired relationship and a certain distance Gab, but I was scientifically and intellectually between me and my family in France. Yet, closer to Gab. My lab management overall “Sensitizing men to looking back, this move to the UK was cer- is inspired by both, as I try to be emotional- tainly the most beneficial decision for my ly close to my coworkers while at the same this effort is absolutely scientific career. I did sometimes regret it in time guiding them scientifically to the best of the past and felt guilt, but for sure, I do not my ability. I think that working with PIs from crucial.” regret it today. I grew so much, scientifically both genders has been a plus. and personally, by going to the UK, the US or the CSHL meetings are exemplary. As a and now Switzerland, that I wish I could go Did you ever consider leaving academia and PI, attending a course on lab management somewhere again! I think the mobility should if so what made you stay? was very informative, not so much on the not be felt as a “must” but as an opportu- I never considered this very seriously. Some- content of the course, but rather because it nity. Very few professions facilitate going times at home we joke about me doing an- made me realize that when you start your abroad like ours does, so if you are moving, other job, as mine is very absorbing, stressful, lab, as much as you try to avoid conflicts, make the most of it! Of course, people with not always family-friendly and hard to share there will be problems with the lab members family restrictions should not be forced to with family members. Nonetheless, this job at one point or another. move. The Americans or the British for ex- offers the possibility to explore the unknown, ample, do not go abroad as much, and yet it is full of surprises and we have a lot of In your opinion do women in science need there are still very good scientists around. In freedom. I also greatly enjoy contributing to gender-specific events/awards? Why? the end, what matters most is the quality of the development of my co-workers. I do not It is a reality that an academic career in the scientific production, not where it was have much of an entrepreneurship drive and science is harder today for women than produced. I am not after money, so the academic path for men. This is just unacceptable and we suits me well. should make sure to help women so that Based on your professional experience so their chances are at least equal. The first far and if you had one advice you could thing is certainly to make women aware of give your younger self what would this be? “I do think that mentor- the situation very early on (possibly already It is a really difficult question, because I am at high school level) and organizing events the sum of my experiences and I would be a ship is crucial, as on this topic is essential. But men need to be different person if I had not lived through all educated, too, and they should help. Sensi- these experiences. I realized that several of scientific mentors show tizing men to this effort is absolutely crucial. my career decisions were based on non-pro- you the path.” My eight-year-old daughter told me recently fessional reasons and maybe this was not al- that she did not want to be a boy because ways reasonable. But from this I also learned they are clearly less smart than the girls in her a lot about myself and this was equally im- Did you/do you have mentors during your class. Clearly, both genders have the same in- portant. So in retrospect, I do not regret any career? How crucial do you think is men- tellectual capacity and it is a real tragedy that period of my professional experience so far. torship for the professional development our system creates extra barriers for women. One piece of advice I got from my stepmoth- in academia? Do you think mentorship for We need to remedy to this actively. er Helen during my postdoc was “When life female scientists should differ from that for gives you lemons, make lemonade”. This is male scientists? What is your experience of balancing career key to progress. I do think that mentorship is crucial, as scien- and family and what are the challenges and tific mentors show you the path. Of course, benefits of “having it all”? sometimes this is very stimulating and posi- I think this is a key question and this aspect is THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 7

Is unconscious bias piercing the pipe? How does implicit bias hinder career progression?

Ana Claudia Marques

Why are women underrepresented in academic research as well, can also slow man and a woman uncovered that males in academic leadership roles (Figure down an individual’s career progression and were 6% more likely to be listed first. This 1)? And is there something we can do the overall diversity of research teams and indicates that women get less credit for their about it? A career in academia is an leadership, the focus of this article is gender contributions on publications (bioRxiv, doi: obstacle race and it’s receivable that bias. Why? Gender bias is the most preva- https://doi.org/10.1101/241554), something not everyone wishes work to spill over lent type of bias and is among the easiest that has been suggested by other studies. most aspects of their life, from how to quantify. Importantly, the general mecha- The likelihood of getting a paper accepted much time they have to accommodate nisms underlying gender biases and how to if the first or last author is a male or a fe- family life or for their hobbies. But why minimize their impact are generally applica- male is also not equal. In the fields of Evo- are women more likely than men to ble to all types of discrimination, making it a lutionary Biology and Ecology, introduction change career after completing a PhD good test case. of double blind peer review led to an over and spending a few years as a post- It is hard to understand why women feel 7% increase in acceptance rates of female doc? Research done to address this discriminated in a society where they can vir- first author papers (Trends Ecol. Evol. 23(1), question suggests women have a few tually access all jobs. This is even more puz- 4–6 (2008)). A recent study analyzing review more hurdles than men to remain com- zling in an academic environment where the reports from eLife indicates that if the last petitive in the academic career race. criteria for career progression are said to be author of the paper is a woman, there is a clear. But the survey in Nature (Nature 562, 3% lower chance of the manuscript being One of the most obvious hindrances to wom- 611–614 (2018)) and other surveys indicate accepted for publication (bioRxiv, doi: https:// en’s career progression is the “baby penal- they do. Why? One possible explanation doi.org/10.1101/400515). ty”. While men are increasingly implicated in comes from a body of research on gender When applying for funding, women also childcare, the decision to start a family still and career. Most of these studies suggest appear to be penalized. After accounting for has a larger impact in women’s careers, be- women may have to jump some extra hur- h-index, funding history and other confound- cause of the time spent away from the lab dles to succeed, which probably contributes ers, Tamblyn and colleagues (CAMJ, 190(16), in late pregnancy and after giving birth. In to fatigue and an increased rate of abandon. E489–E499 (2018)) found that women re- another article in this newsletter we discuss These extra hurdles are there from the ceived lower grant scores than men. The the aims and initial results of a measure the start of the race. For example, in life sciences authors of this study suggest that the lower NCCR implemented to minimize the impact a white male candidate is 9% more likely to scores may be linked to women generally of pregnancy and maternity on female train- receive a response to his spontaneous appli- being perceived as less competent, having ees’ career progression. While we believe this cation than a female candidate (J. of Applied weaker leadership skills, and that evaluation measure will alleviate part of the strain on Psychology 100(6), 1678–1712 (2015)). And criteria may favor male stereotypes. women, we are convinced that by itself this US elite biology male faculty members hire The effect size of this bias, as that of all measure will not be sufficient to repair the 11% fewer female graduates students and the others, is low. However, based on simu- leaks in the pipe. 22% fewer female postdocs (PNAS, 111(28), lations a 4% bias in grant assessment leads Why do we think that? A number of oth- 10107–10112 (2014)). This may in part be to 20% lower grant success (Research Policy, er measures to minimize the baby penalty, due to the moderately lower competency 44(6), 1266–1270 (2015)), which will ulti- for example extended eligibility criteria or rating a female is likely to get compared to mately have a strong impact on the research reentry fellowships for women, have been in a male with an identical CV (PNAS 109(41), led by women. place for a few years now and their impact 16474–16479 (2012)). Perhaps surprisingly, Given that careers in science are built on on women career progression in academia women are as likely as men to take gen- track record, even if these different biases has is so far limited (Figure 1). So what else der-biased decisions (PNAS 109(41), 16474– have relatively moderate effect sizes, they drives women’s decision to leave academia? 16479 (2012)). seriously contribute to our inability to retain A recent survey carried out by Nature may A stellar publication track record will women in academia. Biases on the perceived provide some clues (Nature 562, 611-614 take you a long way into landing that facul- contribution of women to projects, fewer op- (2018)). When questioned about different ty job. But authors are not equal in the eye portunities to engage collaborators/mentors / aspects of their job, women consistently re- of co-authors, reviewers and editors, which sponsors, lower publication acceptance rates ported being less satisfied (on average 5%) likely contributes to the relatively fewer than and fewer grants all contribute to decreased than men. A fifth of the individuals respond- expected women with first author papers in job satisfaction of women that eventually ing to this survey claimed having experienced top journals. For example while 40% of post- leads, in some cases, to a decision to change some kind of discrimination, the most preva- docs in neurosciences are women, only 25% career path. Given the recognized contribu- lent type being gender discrimination (40%), of papers in top journals in this field have tion of diversity to increased performance on which seemed to affect more generally wom- female first authors (bioRxiv, doi: https:// a variety of tasks/challenges, the leaks in the en than men (91% of respondents). While doi.org/10.1101/275362). Is it that women pipe not only impact the lives of women but other types of discrimination (age or race, for work less hard? An analysis of papers where also the potential of future scientific devel- example), which are unfortunately present the first authorship was shared between a opments. THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 8

Is unconscious bias piercing the pipe?

Figure 1: Proportion of women and men in a typical academic career (http://ec.europa.eu/research/swafs/pdf/pub_gender_equality/she_figures_2015-final.pdf)

In the vast majority of cases, the biases implicit.harvard.edu/implicit/) and talk open- events tailored for NCCR trainees and PIs described here do not reflect conscious deci- ly about the topic with colleagues. Another during phase 2. sions to hinder the career of women. Instead, factor that will reduce such biases is critical We believe that addressing the impact of many of these extra hurdles are a conse- mass. When diversity is the norm, such bias- implicit bias on women’s job satisfaction and quence of unconscious biases. As scientists, es are diluted. Increased diversity at higher career progression is as important as tackling we rely daily on our logic and rational think- ranks in academia ultimately relies on unbi- other perhaps more tangible hurdles, such as ing to solve complex problems, and it is thus ased recruiting procedures. Besides specific the baby penalty. We expect that this mul- reasonable to believe such irrational behavior training of search committee members on tifactorial equal opportunities strategy will would not affect our daily professional inter- implicit bias, discussing the job profile early, contribute to increased overall job satisfac- actions. However, most of the studies de- deciding what are the hiring criteria and de- tion across the network and at our scale help scribed here analyzed the behavior of individ- fining the questions that allow to asses these fix some of the leaks in the pipe. uals that like us work in life science research. criteria in a concrete manner, minimizes the Furthermore, a number of legal complaints of impact of bias in hiring and leads to more gender discrimination deposited by women diverse appointments (BioScience, 65(11), at top institutions (for example at the Salk 1084–1087 (2015)). Institute) suggest that unconscious biases are Because we recognize the impact of un- prevalent in academic research. conscious bias on diversity, we have made So how can we address these biases and this topic a central point of the NCCR RNA fix the pipe? Probably the simplest and most & Disease Equal Opportunities strategy for important step is to become aware of our phase 2. We have already started to engage biases and how they impact our professional in training opportunities (refer to our meet- interactions. Test your implicit biases (https:// ing report) and we will organize training THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 9

Lessons learned from the pioneers of the “Pregnancy and Maternity leave compensation” scheme Bridging parental leave in an academic environment Larissa Grolimund, Frédéric Allain and Ana Claudia Marques

A successful career in academia is an obstacle marathon. Becoming a parent impacts everyone’s performance but particularly for women, who need to be away from the lab to take care of a new child, the impact on career progression is more substantial. Taking a baby break during a PhD or postdoc feels like stepping out of the track while already seeing the finishing line and when everyone else is still running. After a maternity leave, new mothers need to quickly regain speed and catch up with their competitors in order to stay in the race.

Most funding agencies and institutions recognize the negative impact of maternity in women’s career progression and most funding schemes now extend eligibility to account for career breaks. What most schemes fail to

“This has kept the project advancing during several months when the work would otherwise have been stopped.”

address, though, is the appreciable setback Figure 2: Pregnancy and maternity impact career progression. of the progression of the research project due to health and safety issues during pregnancy, as well as the frequently complete discontin- uation of the project when the scientist is on maternity leave. In a research environment, assistant will overlap, which should ensure also offers the expectant an opportunity to where competition is fierce and speed is crit- appropriate training of the research assis- build her personnel and project management ical, the delays caused by maternity represent tant who will then continue the project of skills, which will be useful for those aiming a serious burden to women’s career devel- the expectant researcher during the duration a career in academia. The PMLC fills a gap opment. To minimize the negative impact of of her maternity leave. The support scheme for which no other support scheme exists so pregnancy and maternity leave on project helps managing the research project during far. Moreover, it is an ideal extension of the progression, the NCCR RNA & Disease offers maternity leave, prevents its complete inter- Flexibility Grant offered by the SNSF (Swiss a Pregnancy and Maternity Leave Compensa- ruption and promotes a smooth re-entry after National Science Foundation), which is cur- tion support for PhD students and postdocs the baby break (Figure 2). These factors are rently only available to postdoctoral fellows (PMLC). This scheme allows grantees (with also all highly beneficial for the supervisor of with respect to the employment of a support the support of their host PI) to request fund- the expectant researcher whose interests lie person. ing to cover the salary of one research assis- in supporting the careers of his/her young ac- Since its implementation in June 2016, tant during the last 3 months of pregnancy. ademics and generating continuous scientific the NCCR RNA & Disease has issued three During this period mum-to-be and research output on a competitive level. This scheme PMLC grants to scientists of the network. The THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 10

Lessons learned from the pioneers of the “Pregnancy and Maternity leave compensation” scheme

The possibility of employing a support person cover the salary of a full-time employment. continuously from the pregnancy, throughout You can find more information on the “Thanks to the NCCR the maternity leave, and upon return, will not Pregnancy and Maternity Leave Compensa- only allow projects to advance despite moth- tion and the Flexibility Grant on our Equal and my supervisor with erhood, but also improve work-life balance Opportunities website. and, in addition, render the position more his modern attitude attractive for the research assistant. Notably, one of the grantees has mean- I was not obliged to while crossed the marathons finishing line “I think this is real sup- interrupt or abort my and successfully defended her PhD thesis, for which we congratulate her. We will continue port for women and PhD.” to evaluate the impact of the PMLC grant by monitoring the career path of all past and definitely helps my future grantees.

first three grantees have highly appreciated professional career and the unique benefits associated with this sup- future.” port scheme. The temporal overlap between the grantee and the research assistant to- “The overlapping time in wards the final phase of the pregnancy has been judged as extremely valuable for train- the end of the pregnan- ing and knowledge transfer. In most cases, cy is really important to the set goals for the duration of the grant were met and, most importantly, all proj- explain the project in ects progressed during the maternity leave, thus fulfilling the main aim of this scheme. detail and to teach the The grantees underlined the importance of support by their supervisor and a good in- most used methods in formation exchange during maternity leave. The commitment of the supervisor is crucial the lab.” in order to be eligible for the PMLC, as the freed funds released through the maternity allowance will be invested to cover the salary Maximum benefit at no additional ex- costs of the support person during the grant- penses: This support can come at no addi- ee’s maternity leave. Identifying a suitable tional financial costs for the recipient’s su- support person for such a short-term position pervisor. The NCCR RNA & Disease covers has been described as the most challenging the salary of a support person during the last aspect related to the grant. The fact that the three months of a grantee’s pregnancy up first three recipients of the PMLC grants were to a 100% of work-time percentage (max. all PhD students at the time of application, CHF 20'000.–) while the supervisor commits indicates the need for such support measures at all levels of an academic career. Therefore, we have voiced our interests towards the SNSF Directorate for making the Flexibility Grant fully accessible also to PhD students. “It kept the project moving forward without in- terruptions. It is a great “I consider myself very scheme which helps privileged that I could both the student and benefit, because such the supervisor” resources are still not a normal standard in Switzerland and the to use the freed funds released through the maternity allowance to employ the support NCCR sets a great ex- person on the recipient’s project during her maternity leave. The supervisor may use ample.” additional funds to increase the work-time percentage of the support person during maternity leave in case the freed funds do not THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 11

STEMM Equality Congress 2018 International exchange of strategies – Lessons learned

Larissa Grolimund and Frédéric Allain

The underrepresentation of women in tries attended, consisted of keynote speech- changes was discussed in various contexts. leading science positions has been rec- es, panel sessions, workshops and poster A very radical but effective example for a ognized decades ago and is a globally presentations (View our Poster). The speak- promoter to a systemic change was given discussed issue. Organizations, institu- ers presented examples and best practice of by linking governmental research funding in tions and commissions have implement- equality and diversity policy implementation the United Kingdom to the institution’s com- ed numerous measures targeting the with regard to leadership, as well as how mitment to equality recognized through an gender gap. Nevertheless, the progress to integrate equality in an organization and award (Athena SWAN awards). in reaching a gender balance at the top promote a change of culture. Some of the The lessons learned from our experience level has been very slow and the issue presented studies provided rather sobering at the STEMM Equality Congress include the seems persistent. At this year’s STEMM facts and data on inequality such as, for ex- importance of carefully studying the impact Equality Congress hosted by Science ample, how prejudices negatively affect re- of equality initiatives in order to effective- Impact Ltd in Amsterdam, Netherlands, cruitment and peer-review processes (PNAS ly apply them, the engagement of power on October 11th–12th, the NCCR RNA & 109, 16474-9 (2012), Nature 387, 341-3 players, and importantly men, in promoting Disease presented its equal opportuni- (1997)) or nominations for prizes. Others de- a systemic change of culture, as well as the ties action plan and exchanged strat- livered evidence-based suggestions on how benefits of exchanging best practice and ex- egies with researchers, policy makers, to promote a change. These include the need periences with other organizations, which ul- NGOs, academic staff and government for scientific research on existing measures timately face similar challenges with regards representatives from all over the world. (such as for example on the controversially to closing the gender gap. discussed affirmative action, Science 335, This annually held meeting focuses on the 579-82 (2012)) and to act accordingly. A se- discussion of equality, diversity and inclusion ries of talks broached the importance of en- strategies in the fields of Science, Technolo- gaging male leaders as advocates for gender gy, Engineering, Mathematics and Medicine equality. As men fill most leading positions, (STEMM). Although this year’s topic was ded- they have the best prerequisites to impact icated to intersectionality, the predominant cultural and structural changes. After all, the and recurring theme throughout the pre- disadvantages related to women’s underrep- sentations and discussions remained gender resentation and the associated loss of diver- inequality in STEMM. The two-day meeting, sity affects all genders. Promoting inclusion to which over 280 participants from 28 coun- and diversity by structural and organizational

Role models and mentoring Inspiration by role models

In the context of the NCCR seminar series, we regularly organize female scientist lunches with women speakers to provide junior women scientists the opportunities to meet outstanding and inspiring female researchers. Attendees evaluate this initiative very posi- tively. The latest female scientists lunches took place in Bern and Zurich on December 3rd and 4th with Prof Dr. Marina Rodnina (Max Planck Institute for Biophysical Chemis- try, Göttingen, Germany). Visit our Webpage to find out more about the NCCR RNA & Disease seminar series. If you are interested in attending a lunch with a speaker, please contact the NCCR office (office@nccr-rna-and-disease.ch) at the latest one week before the seminar. Attendees of the lunch for female scientists with Marina Rodnina (5th from left) in Bern on December 3rd. THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 12

Research highlights Research highlights from NCCR laboratories Roland Fischer

Too much Stress and Pressure

Some people with amyotrophic lateral of choice for release of inter-cranial pressure sclerosis or frontotemporal dementia after brain trauma, may trigger the initial accumulate deposits of the nuclear pro- events that lead to FTD. Indeed, a strong as- tein FUS in the cytoplasm. What drives sociation between brain trauma and FTD has this relocation? Researchers led by Mag- been described in the past years by several dalini Polymenidou at the University of groups, but no mechanism that could explain Zurich blame osmotic pressure. this association has been described to date. It is also known that hyperosmolarity can trig- UniProt is a bit vague when it comes to the ger the release of proinflammatory cytokines. RNA-binding protein FUS: “May play a role Inflammation is a known risk factor for many in maintenance of genomic integrity.” What neurodegenerative diseases. is certain: In healthy cells, FUS is transport- ed to the nucleus and binds to both DNA Hock et al., (2018) Cell Reports 24, and RNA, mediating the synthesis of a whole 987–1000 range of proteins. But in ALS and frontotemporal dementia – a common dementia – the entry of FUS into the nucleus of nerve cells is compromised. Aggregates of FUS and RNA transform into so-called stress granules. The role of these granules in the pathological process is still unclear. Physiological condition Frontotemporal dementia is the second most common type of dementia after Alzhei- mer’s disease and typically affects individuals Nuc under 65 years of age. In a subset of these Cyt patients, affected neurons present a characteristic pathology with cytoplasmic mislocal- TNPO ization and aggregation of the RNA-binding FUS / other passive exit TNPO-mediated import protein FUS, which normally resides in the TNPO cargo nucleus. Since no mutations in FUS or any Hyperosmotic condition other proteins have been described in these Neurons Astrocytes cases, the trigger of FUS mislocalization that likely initiates the cascade of events leading to neuronal dysfunction and death remains enigmatic. The new study by the Polymenidou group, published in Cell Reports, shows that hyper- tonic stress leads to cytoplasmic translocation and loss-of-function of neuronal FUS. Sur- prisingly, and opposite to current thinking, Cytoplasmic accumulation of No cytoplasmic accumulation of TNPO and its cargo TNPO and its cargo the osmosis-triggered cytoplasmic shift of FUS is independent of stress granule formation or the molecular pathways induced by Nuc Nuc hyperosmolarity in cells. FUS mislocalization could be the first Cyt Cyt step toward disease, Polymenidou suggested. She believes osmotic stress acts as the trigger that sends FUS to the wrong place, passive impaired TNPO- passive functional TNPO- where a second stressor could then cause it exit mediated import exit mediated import to aggregate. An important implication of the work for public health is the fact that Figure from Hock E.-M. et al. (2018) Cell Reports, 24(4), 987–1000 published under the CC BY 4.0 hyperosmolar therapy, which is the method license THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 13

Research highlights

Ribosomal proteins taking over

In a recently published Science paper, particular interest, especially in extreme cases shared by all ribosomes, which will help de- David J. F. Ramrath and Moritz Niemann as T. brucei. In these mitoribosomes featuring fine the most essential functional elements. from the Ban and Schneider groups the smallest known rRNAs, the severe rRNA The trypanosomal translational machin- shed light on the evolutionary shift reduction is accompanied by the recruitment ery adopted unusual solutions to accomplish toward protein-based architecture in of many additional proteins. Trypanosomal some basic protein synthesis mechanisms. trypanosomal mitochondrial ribosomes. mitoribosomes therefore represent an excel- Notably, the structure unveils two intriguing lent system to reveal the minimal set of rRNA functional details: Their nascent polypeptide Mitochondrial ribosomes (mitoribosomes) are and protein elements essential for ribosomal exit tunnel branches into two exits – it is more closely related to bacterial ribosomes function and to investigate how ribosomal conceivable that nascent proteins with dif- than to eukaryotic cytosolic ribosomes. How- proteins compensated for the missing rRNA. ferent characteristics take different paths. ever, they have undergone extensive struc- To address these questions, the Ban and Furthermore, in a subpopulation of isolated tural and compositional change throughout Schneider groups determined the atomic small-subunit particles, mitochondrial initia- evolutionary time. Most notably, mitoribo- structure of the mitoribosome from T. brucei tion factor 3 was observed interacting with somes have acquired a large number of mi- using cryo–electron microscopy. The structure the decoding center via its unique C-terminal tochondrial-specific ribosomal proteins, and shows how the proteins have taken over the extension. This might compensate for the es- the mitoribosomal RNA has been shortened role of architectural scaffold from the rRNA: sential function of initiation factor 1 that is in many organisms, including mammals, but They form anautonomous outer shell that absent in all mitochondria. most extensively in Trypanosoma brucei, the surrounds the entire particle and stabilizes parasite that causes sleeping sickness. the functionally important regions of the Ramrath and Niemann et.al., (2018) Science Because mitoribosomes are conserved to rRNA. The paper reveals the “minimal” set 362, eaau7735 a high degree, the observed variability is of of conserved rRNA and protein components

Image kindly provided by David Ramrath THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 14

Research highlights

If it’s complex, it’s possibly quadruplex

‘If G-quadruplexes form so readily in vitro, G3-tracts (G3-quadruplexes). Stable G3-qua- The group identified 35 putative G2-tract Nature will have found a way of using them druplexes (i.e. strong enough to stall reverse quadruplex structures in the 5’ and 3’ UTRs in vivo’, said Nobel prize winner Aaron Klug transcriptase) in eukaryotic cells have been of genes in the polyamine (PA) biosynthesis already some decades ago. The Hall group shown to be frequently unwound; so the pathway. Using cellular reporter assays they from the Institute of Pharmaceutical Sciences physiological relevance of quadruplex struc- could identify twelve of these covering eight at ETH Zurich has now clarified one of these tures should not be automatically inferred PA synthesis proteins that altered reporter functions: the control of the polyamine bio- from their stability. Consistent with this, activity in comparison to mutants. Strikingly, synthesis pathway by G2-quadruplexes. several hundred putative metastable RNA most of these structures had the effect to re- G2-quadruplexes have also been predicted duce PA levels. This suggested they might act G-quadruplexes are naturally-occurring struc- throughout the transcriptome. So far, few in unison as regulatory elements to control tures found in RNAs and DNAs. Over the past G2-quadruplexes have been studied in detail PA homoeostasis. two decades biologists and bioinformaticians biophysically, structurally and functionally. The study thus expands the repertoire of have unearthed substantial evidence for As reported in the open-access jour- regulatory G-quadruplexes and demonstrates G-quadruplexes as important mediators of nal eLife, the Hall group has investigated a how they act in unison to control metabolite biological processes. This includes telomere grouping of G2-motifs in the untranslated homeostasis. More specifically, the group’s damage signaling, transcriptional activity, regions (UTRs) of eight genes involved in findings reveal a previously unrecognized and splicing. Although their structures are polyamine biosynthesis, and concluded that mechanism of PA self-regulation. They ex- difficult to characterize in vivo, G-quadru- several likely form novel metastable RNA pect that such mechanisms through G-qua- plexes are recognized as important elements G-quadruplexes. They performed biophysical druplexes may be a common feature in other regulating gene expression, and they are characterizations of their properties, com- metabolic pathways. increasingly linked to diseases. As in DNA, paring them to a reference G-quadruplex regular RNA G-quadruplexes have shown to and discovered how some of these motifs Lightfoot et al., (2018) eLife 7:e36362. be highly stable due to stacked planar ar- are able to regulate and sense polyamine rangements connected by short loops. More levels, creating feedback loops during poly- interestingly still, reports of irregular qua- amine biosynthesis. With the key help from druplex structures are increasing and recent the Allain group, the team demonstrated genome-wide studies suggest that they in- using NMR spectroscopy that one particular fluence gene expression. Thousands of such long-looped quadruplex in the AZIN1 mRNA motifs have been identified, the majority co-exists in salt-dependent equilibria with a of which comprised canonical short-looped hairpin structure.

Image kindly provided by Timo Hagen THE NCCR RNA & DISEASE MESSENGER, No. 10, December 2018 15

Announcements

People Upcoming events organized or supported by We congratulate Michael Hall on receiving the 2019 Charles Rodolphe the NCCR RNA & Disease Brupbacher Award for Cancer Research. > NCCR Seminar Series: Congratulations to Martin Jinek and Lukas Jeker for being awarded Jennifer Doudna (University of California, Berkeley, USA) an ERC Consolidator Grants. March 3, University of Bern & March 4, 2019, ETH Zurich We would like to welcome Francesco Bertoni, who is a group leader Alexander Mankin (University of Illinois, Chicago, USA) at the Institute of Oncology Research (IOR), Bellinzona as a new as- March 18, University of Bern & March 19, 2019, ETH Zurich sociate member of the NCCR RNA & Disease. His group researches Reinhard Lührmann (Max Planck Institute for Biophysical the genomics of lymphomas. Chemistry, Göttingen, Germany) April 1, University of Bern & April 2, 2019, ETH Zurich Michaela Frye (University of Cambridge, Cambridge, UK) Support Grants May 13, University of Bern & May 14, 2019, ETH Zurich Please visit our webpage for more information on the Lab exchange 3rd NCCR RNA & Disease summer school “RNA Regulation program, the Doctoral mobility grant and measures in equal oppor- in Health and Disease: Genome architecture and gene expres- tunities. sion – RNA turnover – Epitranscriptomics – Phase separation", August 26 – 30, 2019, Saas-Fee (Registration opens soon)

Swiss RNA Workshop Special NCCR TransCure and RNA & Disease Seminar The 20th edition of the Swiss RNA Workshop will take place on Jan- Gail Robertson (Dept. of Neuroscience, University of Wisconsin, uary 25, 2019, in Bern. Keynotes will be given by Eric Miska (Gur- USA) January 14, 2019 University of Bern, EG 16, 16.30 –17.30 don Institute, University of Cambridge, United Kingdom) and Alena Shkumatava (Curie Institute, Paris, France). Registration and abstract NCCR RNA & Disease Internal Events submission is closed.

> Joint retreat with the with the Vienna RNA research community, Visit the workshop’s website for more information. January 30 – February 3, 2019, Fuschlsee, Austria > NCCR RNA & Disease “Séance de Réflexion”, March 15, 2019, Haus der Universität, Bern

Jobs PhD program in RNA Biology The next application deadline is July 1, 2019. Find out more on the PhD program website

Update links

Postdoctoral Position – circadian clocks & RNA biology – Gatfield lab University of Lausanne

PhD and Postdoc Positions – Gene Regulation by RNA modifications – Pillai Lab, University of Geneva

Check the jobs’s section of the NCCR RNA & Disease webpage for other openings.

IMPRINT Office Bern University of Bern The National Centres of Competence Departement of Chemistry and Biochemistry in Research (NCCR) are a research instrument Freiestrasse 3, CH-3012 Bern of the Swiss National Science Foundation Office Zürich NCCR RNA & Disease ETH Zürich Phone: +41 31 631 38 12 Institute of Molecular Biology & Biophysics [email protected] ETH-Hönggerberg, HPP L15 www.nccr-rna-and-disease.ch Otto-Stern-Weg 5, CH-8093 Zürich