BSCB Magazine 2021 BRITISH SOCIETY FOR CELL BIOLOGY
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BSCB Magazine 2021 News 2 Features 6 Book and game reviews 26 Meeting Reports 27 Summer Students 32 Society Business 39 Editorial Welcome to the 2021 edition of the BSCB magazine. and autophagy. Please see page xx for more infor- Front cover: Structured Illumination Microscopy (SIM) It’s been an incredibly eventful year, full of challenges mation. Meanwhile in the BSCB we have continued image of a HeLa cell expressing both personal and professional for all of our working, albeit on zoom, and are delighted to launch mScarlet localised to the members. For the BSCB in particular it has been our two new medals and announce the winners of mitochondrial matrix (red). a major time of change. The first lockdown was these. We discuss how the medals were designed Mitochondrial membranes are shown in green (MitoTracker announced so close to our Spring meeting in 2020 on page 4. As ever we also feature interviews with Green), cell nuclei are labelled we ended up deferring it to 2021. Our Dynamic Cell our Hooke and WICB winners on pages 6 and 9 with DAPI (blue), and tubulin meeting was jointly organised with the Biochemical and send both Ian Chamber and Yanlan Mao well is shown in cyan. The image Society and ran from 14–19th March 2021. As deserved congratulations. We welcome new PhD and was taken using a DeltaVision always, the remit of the meeting was broad, with Postdoc reps to our committee, see page 5, as well OMX v4 imaging system (GE Healthcare). a focus on cellular dynamics and stimulated novel as new committee members Dr Tom Nightingale, Dr collaborative approaches and the application of new Victoria Cowling and Professor Giampietro Schiavo. The image was taken by Hope technologies to established fields. The meeting was Sadly we also say goodbye to several of our time Needs, University of Bristol, well attended and we would like to thank everyone served committee members including Judith Sleeman and was the winner of hte BSCB Image Competition who was able to make the meeting virtually. our web editor, Andrew Carter, our Membership 2020. See page 14. Due to the ongoing pandemic, we have made Secretary, Julie Welburn who managed the Honor the decision to change our plans for the Cell la Vie! Fell awards for several years this year Anne Straube Above: Ian Chambers, Hooke Meeting with the French Society for Cell Biology will step down after excellent service as meetings award winner; BSCB medals; again. The meeting in September will now become secretary to be replaced by Susana Godhino. BSCB imaging competition winners; Cell la Vie meeting. a one-day online meeting on 23rd September, Last summer, our summer studentship coordinator, organised by ECR’s from both British and French Maria Balda, made a bold initiative of suggesting we Societies. Details are still being worked out and will continue to offer our summer studentships online. be communicated when finalised as well as updated This resulted in some excellent but quite different on the meeting website: https://www.atoutcom.com/ projects to read about what our students got up to cell-la-vie/. Please follow our the BSCB twitter feed please see page 32. We also have meeting reports @official_bscb for updates. from the last few in person meetings our members We have been really inspired by our members were able to attend and look forwards to hearing your response to the Covid 19 pandemic. Several of our response to our online meetings and members survey early career members have taken the opportunity to in 2021. move seminars online and form new initiatives for Enjoy reading this issue of our magazine and hope scientific dfiscussion. This has resulted in a democra- to see you virtually at Cell la Vie online. tisation of science and widened access for discussion in topics such as cilia, molecular motors, cell motility Ann Wheeler – Magazine editior Magazine Editor: Ann Wheeler Production: Giles Newton, Deadlift Media Printer: Hobbs BSCB website: www.bscb.org 1
Society News NEWS BSCB President’s Report 2020 I hope you enjoy this year’s Women in Cell Biology Early in visualising BSCB Magazine, which provides Career Medals to award and and studying cell insight into the many activities celebrate. The 2020 winners biological results that you can get involved in as were Ian Chambers (Hooke – see reports from a BSCB member. I want to take Medal, University of Edinburgh) these students on this opportunity to describe and Yanlan Mao (WICB page 32. some positive BSCB events Early Career Award Medal, in 2020 and look forward to Laboratory for Molecular Cell As a BSCB BSCB events in what will be Biology, UCL). Ian’s research member, your happening in 2021. focuses on the mechanisms registration fees for our meetings of stem cell pluripotency. this year are substantially We launched two new annual Yanlan investigates the discounted, so please do take prizes in 2020: The Raff Medal mechanics of tissue growth and advantage of this benefit by for PhD students and the regeneration, using an array of registering for Dynamic Cell BSCB Postdoctoral Researcher interdisciplinary approaches. IV (March 2021) and/or ‘Cell Medal. There was intense We had originally planned to la Vie’ (September 2021). If competition for the prizes, with present the 2020 winners you are a PhD student or many excellent candidates, with their medals at our 2020 postdoc, you can apply for an reflecting the high quality of annual meeting. Sadly, we Honor Fell travel award to help research carried out by BSCB had to make the decision to fund your registration costs PhD students and postdocs. I postpone this meeting for and travel for any conference, am delighted to announce that a year, which would have meeting, or workshop relevant the Raff Medal was awarded been our first in partnership to cell biology, including a to Flora Paldi (University of with a non-UK society, the BSCB meeting. Group leaders Edinburgh) and the Postdoctoral French Society for Cell Biology who do not currently have Researcher Medal to Agathe (SBCF). It is now scheduled for any conference funds in their Chaigne (Laboratory for September 2021 (see page 3 grants are eligible to apply for Molecular Cell Biology, UCL). for more information). Instead, Company of Biology Travel The medals will be awarded they will present their research Awards. We are also awarding at our virtual Dynamic Cell IV and receive the medals virtually these for registration for virtual meeting (14–19 March 2021), at our Dynamic Cell IV meeting. online scientific conferences/ accompanied by a short talk meetings. Please visit our by each of the medal winners. I am also delighted to announce website to find out more about These prizes were proposed the 2021 Medal winners: these awards, as well as other and championed by our BSCB Stephen Royle (Hooke Medal, ways you can get involved with committee PhD student rep University of Warwick) and the BSCB. Joyce Yu and our postdoc Vivian Li (WICB Early Career rep Gautem Dey. We are Award Medal, Crick Institute, I enjoyed meeting many of you very grateful to them for their London). They will give their online at Dynamic Cell IV and commitment and attention to award presentations and receive look forwards to seeing you detail from the first concepts to their medals at our 22–24 again at ‘Cell la Vie’ online in the advertising and awarding of September 2021 meeting in September 2021 and in Paris the prizes. Joyce and Gautem Paris, ‘Cell la Vie’. in 2022. finished their time on the BSCB committee at the end of 2020, In contrast to most UK and our new reps, Rowan Taylor societies, we decided to go (PhD rep) and Alex Fellows ahead with awarding our BSCB Anne Ridley (postdoc rep) have coordinated summer studentships for the BSCB President the design of the two new summer of 2020. This enabled medals, which will be ready to 12 undergraduate students to award to our medal winners in carry out 6–8-week research March. projects with the laboratories of BSCB members. Most of these The ongoing pandemic means ended up being data analysis that we now have a backlog projects online, which gave the of BSCB Hooke Medals and students valuable experience 2
BSCB News NEWS was online, providing a rare opportunity for us to be photographed, or captured in a screenshot Lockdown did not stop the together. If you are BSCB from working. Instead we interested in getting more moved online. During Lockdown involved in the BSCB the BSCB twitter feed provided committee please contact a hub for the Cell Biology our Secretary. community’s work in keeping scientific discourse and debate The BSCB opened going. In particular several two new medals, the journal clubs and seminar series Raff award and the which sprang up. Postdoctoral Researcher medal to applicants. Several BSCB events went Several applications were online, including our summer received and the winners meeting on 23 September, Stephen Robinson, UEA, has projects. Dynamic cell which will be announced at our Spring organised by ECRs from both taken over from Judith Sleeman was postponed from last year meeting. British and French Societies. as our Digital content, Imaging is now happening online to Details are still being worked competition and writing find out more about what is To support researchers during out and will be communicated competition manager; we happening please see our lockdown the BSCB launched when finalised as well as would like to thank Judith for webpage. a Covid assistance fund – see updated on the meeting all of her work and welcome below. website: https://www.atoutcom. Stephen on board. Since we The BSCB committee went com/cell-la-vie/ have had to postpone several fully online, as the committee Due to the ongoing pandemic, of our meetings and labs have membership is taken from we have made the decision to The main Cell la vie! meeting been affected by closures, we the whole of the UK its not change our plans for the Cell will be postponed until 21–23rd have decided to extend our uncommon for one or two la vie! meeting with the French September 2022, to be held deadline for the imaging writing members to join our twice Society for Cell Biology in at the Institut Pasteur in Paris competitions to 30 June 2021. yearly committee meetings September 2020. The meeting as before. Full speaker list and remotely. However for our in September will therefore registration details will again be November meeting everyone now become a one-day online advertised in due course. The Company of Biologists launches new COVID Assistance journal websites Fund The BSCB was concerned about the additional pressures the current and ongoing COVID restrictions are placed on those with caring responsibilities. To mitigate this, the BSCB announced an initiative to provide financial support for those in this situation, termed the Covid Assistance Fund. This funding could be used to cover any additional costs incurred, for example to support extra childcare or carer support. We offered grants of £200, from a total fund of £5,000, with application deadlines every 2 weeks. Preference was given to The Company of Biologists has of Cell Science, Journal of with additional functionalities, students, postdocs, early career migrated its leading journals Experimental Biology, Disease such as split-screen view for PIs, and those with extraordinary to the hosting platform of Models & Mechanisms, and easy data reference. Moving circumstances. The funding Silverchair. Biology Open. are available platforms has also given the was well received, and we were via https://journals.biologists. Company’s journals access to a able to provide support to five The websites of the five com and have been given range of partner integrations via BSCB members when they most journals – Development, Journal an updated, modern design, Silverchair. needed it. 3
Designing the Postdoc and NEWS PhD Medals Our PhD reps, Alex and Rowan wanted to add some creativity have taken on the challenge to the conventional forms of of designing the medals for scientific communication, our new Raff and Postdoc with the aim to spark interest awards. To help them realise inside and outside the scientific our aspirations they engaged the community. Her drawings are spend many hours in a dark Designing the Post-doc assistance of Beata Mierzwa, designed illustrate scientific microscope room and capture research medal Postdoctoral Fellow and Science themes with an artistic the most beautiful images I can Artist at the Ludwig Institute twist, and aim to highlight find, and compile them into “The aim here was to illustrate La Jolla, USA. Beata is also an fundamental scientific aspects aesthetic patterns.” the international nature of AAAS If/Then ambassador for in an unconventional way. excellence in science whilst women in Stem: She creates her drawings for Designing the PhD award- Raff also recognising that Postdocs everyone to enjoy – for scientists medal contribute to the community in Beata Mierzwa, is a molecular to appreciate biological findings many ways. The words in Latin biologist working on cell division in a refreshing way, and for “I tried to highlight several different stand for ‘knowledge’, ‘teaching’ of animal cells. She combines non-scientists to discover the aspects related to Professor Martin and ‘community’.” her two passions – science beauty in fundamental biological Raff’s discoveries. The membrane and art – to create unique and principles. and Ig receptor highlight his work To see more of Beata’s unconventional illustrations. on B and T cells, as well as the beautiful work see https:// During her research, she Beata says “Every drawing is discovery of the fluid nature of beatascienceart.com/ realized that these two have an experiment! I create my membranes. The Schwann cell a great deal in common and artworks by making a detailed going around the medal refers to Her shop is at https://www.etsy. that combining these passions pencil drawing on paper with the first antibody markers that com/shop/beatascienceart creates a unique way to colors added digitally. For my were able to distinguish neural cell communicate science. She microscopy fashion, I types.” Meetings Calendar 2021–22 March 2021 June 2022 The Dynamic Cell Creative Science Writing Workshop 14– 19 March 2021. Online 26–29 June 2022. Wiston House, West Sussex, UK BSCB Meeting Company of Biologists sponsored workshop bscb.org/meeting/the-dynamic-cell-iv/ September 2022 May 2021 Cell La Vie Cell Dynamics: Host-Pathogen Interface 21–23 September 2022. Institut Pasteur, Paris 23–26 May 2021. Pestana Palace Hotel, Lisbon, Portugal. BSCB Meeting Company of Biologists sponsored workshop www.biologists.com/meetings/celldynamics2021/ BSCB-supported one-day September 2021 meetings Cell La Vie British Microtubule meeting 23 September 2021. Online Postponed to May 2021 BSCB Meeting Cilia meeting Held as regular virtual meetings, in person meeting postponed October 2021 to May 2021 The Cytoskeleton Road to Neuronal Function North of England Cell Biology meeting 17– 20 October 2021. Wiston House, West Sussex, UK Transferred to monthly and virtual for this year Company of Biologists sponsored workshop www.biologists.com/workshops/october-2021/ 4
NEWS Our new Postdoc and PhD reps ALEX FELLOWS model of ALS. Interestingly, Her research is focussed on IGF1R influenced trafficking by understanding the cellular and My research focuses on altering the levels of BICD1, molecular basis of inherited intracellular trafficking in a dynein adaptor protein. In retinal diseases (IRD) and neurons and how this process 2019, this work led me to join ciliopathies. Rowan uses is regulated by the motor to the Carter lab (MRC-LMB) in CRISPR/Cas9 gene editing in protein dynein. The precise Cambridge for my postdoc as induced pluripotent stem cells movement and spatial I became incredibly interested to introduce disease variants positioning of cellular cargo in how dynein regulated this in primary-cilia associated such as mitochondria, RNA and process and wanted to continue genes. These cells then undergo endosomes are essential for this research. I now combine in directed differentiation to form the survival and maintenance vitro reconstitution, structural retinal and renal organoids, of neurons. Consequently, and neuronal cell biology 3D cell models, in order to perturbations of intracellular engaging events for the early techniques to further explore analyse the molecular bases trafficking have been linked to career research members of this process. of disease pathogenesis in a both neurodevelopment and the BSCB. Her key aim as PhD physiologically relevant cell neurodegenerative diseases and rep is to ensure postgraduate model. She will be carrying out thus represent an important researchers are able to fully ‘I’m really proud to represent a placement in the lab of Prof area of research. benefit from the network of the cell biology Postdoc Ronald Roepman at Radboud University, Netherlands later peers accessible from the I began working on intracellular community and want to help this year to work on introducing BSCB, to enrich their personal trafficking during my PhD in support it anyway I can. endogenous tags, such as and career development. She is the lab of Giampietro Schiavo This will include continuing SNAP-tag and HALOTag, to particularly looking forward to at UCL. The Schiavo lab to promote the new Postdoc disease genes for advanced planning career workshops and works to understand how award, further developing the proteomics and microscopy. the early career symposium for axonal transport deficits lead early career researcher section Dynamic Cell IV in the Spring. to the development of the on the BSCB website and Rowan also works as a STEM neurodegenerative disease setting up new mini-symposium Rowan is excited to work with Educational Outreach Fellow amyotrophic lateral sclerosis for ECR career development. If the BSCB to is keen to hear at the University of Leeds. This (ALS). My work involved using anyone has an ideas or ways from postgraduate researchers role involves engaging with light microscopy techniques they think I could help please as to what she can do for school students to encourage both in cell and in vivo to get in contact.’ them within this role. She interest in STEM subjects measure transport in neurons. looks forward to meeting you ROWAN TAYLOR by creating and delivering I uncovered a new regulator virtually at the upcoming workshop content at the of intracellular trafficking, the Rowan Taylor is a final year BSCB events. You can follow university and in schools. She insulin-like growth factor 1 PhD student in the new Leeds Rowan’s research and outreach hopes to apply these skills to receptor (IGF1R), which could Centre for Disease Models activities on her twitter feed @ the role of PhD representative be targeted to rescue trafficking at University of Leeds, in the ResearchRowan. at the BSCB to plan effective, deficits found in a mouse lab of Prof Colin A. Johnson. Schools news: The BSCB/CIMR CELLpics website for schools On 12 January 2021 the Adobe of other countries including the ‘pointing device’. A big request! and Matthew added-in a useful Corporation closed down its USA, Brazil, Malaysia, India A then member of the BSCB highlighting device. FLASH facility. With the demise and Australia where we enjoyed Committee and Director of the of FLASH we have lost the joint link with the Australian Society Cambridge Institute for Medical Sadly it has now all gone, and as BSCB/CIMR [Cambridge Institute for Cell Biology. The text was Research (CIMR), Professor Paul far as we know there is nothing for Medical Research] website translated into Norwegian and Luzio, said “leave it with me”. except very advanced graphics for schools about cell biology. used on the website of the Paul magnificently supported the programmes that could replace National Education Department. project by asking and permitting it. Electronics can be a great Using its unique GridPoint In the UK it was listed by his extremely able Microscopy terminator. Information from alpha-numeric ‘Cross-hairs’ the Open University for their Facility Manager, Matthew Ancient Egypt, Rome and Greece location device, students students, on JISC and ‘Merlot’ Gratian, to help me. I would can be deciphered and read, but and teachers could locate in the USA. It was also referred select the micrographs, many not CELLpics! precisely a particular point on to in a highly regarded textbook kindly supplied by The Wellcome the micrographs shown and for students studying biology at Trust, write the text and explain David Archer, Schools Liaison highlighted. Examples included A-level. what I would like to point to on Officer. mitochondria, endoplasmic the micrograph. I had it in mind reticulum and Golgi apparatus. CELLpics had its origins in a that I would like to have a cross- request I made to the BSCB hairs device coupled with the In its heyday (2015/16) it Committee for a facility to show ability to define a grid reference attracted nearly 7,000 viewers micrographs in full colour with point. Matthew came up trumps a year from the UK and a variety explanatory text and some sort of and ‘GridPoint’ was developed 5
Hooke medal winner 2020: FEATURES Ian Chambers Ian Chambers received the 2020 Hooke Medal, established to recognise an emerging leader in cell biology. Ian studied biochemistry at the University of Strathclyde in Glasgow, and then did his PhD in the laboratory of Paul Harrison at the Beatson Institute for Cancer Research, also in Glasgow. He studied the control of gene expression during the differentiation of erythroid pre- cursor cells, discovering that the amino acid selenocysteine is encoded by UGA, which until then was thought to work only as a termination codon. Ian did his post-doctoral work on the regulation of the human immunodeficiency virus (HIV) with Paul Berg at Stanford University in California, USA. In 1991, he returned to Scot- land to work on stem cell regulation with Austin Smith at the Centre for Genome Research (later the Institute for Stem Cell Research) at the Uni- versity of Edinburgh, UK. During that time, Ian identified the transcription factor Nanog, which directs efficient embryonic stem cell self-renew- al. Ian started his research group in 2006 at the University of Edinburgh, where he is also a Professor of Pluripotent Stem Cell Biology. Ian’s laboratory tries to understand the regulatory net- works and transcription factors that control the identity of pluripotent embryonic stem cells, and how these made me curious about science was a BBC television dramatization of Louis Pasteur’s life, which I found very interesting, and it was through listening to it that I started modulate cell fate decisions during the differentiation thinking about what an amazing person Pasteur was. process. Ian is now the Head of the Institute for Stem Cell We’d all learnt about pasteurisation, but the fact that Research at University of Edinburgh, an EMBO member Louis Pasteur was able to use reason to discover the basis and a Fellow of the Royal Society of Edinburgh. of a disease like rabies without being able to really see any of the causative agents involved was quite a profound What inspired you to become a scientist? thing for me. I still find it quite amazing that by pure Most of my schooling was in Ayrshire, and because reason he was able to advance knowledge. Alexander Fleming was born in Ayrshire, we heard about penicillin from an early age. However, there was one What questions are your lab trying to answer just now? instance in secondary school, when the chemistry teacher We want to know, and this is something that many other had everyone in the class around the front bench and he people are trying, too, how a cell with more than one fate asked what would happen if he mixed two measuring can choose to do one thing rather than another. Specifi- cylinders, one with dried peas and the other with dry rice cally, what we’re interested in is how transcription factors grains. He said, “I’ve got 100 ml of each, so if I pour one work – how these molecules interact with other partner into the other I’ll get 200 ml, won’t I?” and I said “No, I proteins and also with DNA to deliver function. And how disagree because there’s space between the peas for the these protein–DNA complexes connect to RNA polymer- rice to fit in.” He was talking to us about differently sized ase is an important part of the puzzle that I don’t believe atoms and how space exists between atoms. I thought, has been fully worked out yet. “Anybody can do this, this is easy.” Another thing that 6
FEATURES What has been the most influential publication or work setback. When we were designing the experiment that in your field recently? finally led to the cloning of Nanog, we decided that we We’re understanding more and more about many of the would increase our chances of catching something by molecules that are involved in embryonic stem cell (ESC) casting as wide a net as possible. We knew that self-re- self-renewal and the decisions to differentiate. Obviously, newal was more efficient when ESCs were grown on top the most important experiment was the one that Kazu- of a heterologous feeder layer of fibroblasts. We didn’t toshi Takahashi and Shinya Yamanaka did 14 years ago really know why that was at the time, but we thought it (https://doi.org/10.1016/j.cell.2006.07.024) [where they might be because fibroblasts need to be in direct contact induced pluripotent stem cells from fibroblast cultures]. I with the ESCs in order to provide them with a signal think more recently, in terms of gene transcription, there that optimised self-renewal. Anyway, that worked. We has been a lot of excitement around the concept of phase cloned Nanog from the resulting library. There’s nothing separation in biochemical systems; this has received a like failure to sharpen your mind. Thinking things through lot of attention but it’s not uncontroversial. The idea that from a previous experiment helped us do things better. high concentrations of molecules can somehow gather The ‘eureka’ moment was when we sequenced individual into a different phase, with separate physical proper- plasmids from the self-renewing colonies. There were ties from the liquid around them, and be important in multiple copies of a single transcription factor in there so controlling cellular events is interesting from the point of at that point I knew that we had it. But I didn’t talk about view of transcription. One of the experiments that has it and I didn’t tell my boss about that for several months been used to support phase separation is shown in the until it was totally nailed down. paper from Takashi Fukaya and Mike Levine (https://doi. org/10.1016/j.cell.2016.05.025). They showed that a The ‘eureka’ moment from my PhD was quite interest- developmental enhancer placed between two separate ing. I was studying the basis of differentiation of red cell promoters would activate transcriptional bursts from both precursors by focussing on the control of gene expression promoters simultaneously. That certainly suggests that of non-globin genes (many groups were already working promoters are activated in response to whatever that on globin). We didn’t know much about the gene I was enhancer-emanating event is, and people have used that working on. So, one of the things I had to do was se- argument to say that phase separation may occur, but I quence the gene. This was in the mid-1980s, so we were think there are other possibilities; for instance, local con- running our own sequencing gels. There was something centrations of regulators may be sufficient to explain that. that was puzzling me because I could see a stop codon right in the middle of the open reading frame. I thought it In terms of development, if I had to pick out one paper must be a mistake. We ran homology searches and found from the last ten years I would choose the paper from nothing. Finally, we got a match to a protein that had just Emma Farley, again from Mike Levine’s lab, which was been published, but we couldn’t access the paper at the published in Science in 2015 (https://doi.org/10.1126/ University of Glasgow, so I had to go across the city to the science.aac6948). It talks about the sub- optimisation of University of Strathclyde library, which was a 40-min bus developmental enhancers. It’s a really great piece of work. ride. Once I had the photocopied paper, I looked at the They study a particular enhancer in the sea squirt Ciona, sequence and thought ‘there’s this funny amino acid and and show that if they increase the affinity of transcription it’s sort of in the same position as this funky stop codon factor-binding sites or optimise the spacing between is’. I was a wee bit excited, so I zipped across the city transcription factor binding sites within the enhancer, the back to the lab, which took me another 40 min, and by enhancer works better. That’s no surprise, right? But then this time it was about eight or nine o’clock at night. I put they show that development doesn’t work properly and it all together but at that point I think there was only one cells don’t perform the way that the developing Ciona other PhD student in the lab. But that was definitely an would like them to. I think that is quite profound and has ‘eureka’ moment. echoes in other systems. For example, in ESC cultures, some cells self-renew while others differentiate. We can You mentioned failure is an opportunity to learn. How make self-renewal uniformly efficient by increasing the do you mentor your students or postdocs to deal with concentration of some pluripotency transcription factors, mistakes or failures? such as Nanog, or by halving the concentration of another We just have to be rigorous and systematic. There’s noth- pluripotency transcription factor, Oct4. What this means ing wrong with failure; we learn more from our failures is that the normal transcription factor circuitry in ESCs is than we do from our successes, so it’s an opportunity suboptimal and that the demise of the pluripotent state is for ‘growth and self-realisation’. We always have to try encoded within the network of transcription factors that to look at the evidence as critically as we can and try to are required to maintain pluripotency. In the embryo, the figure out what’s gone wrong. Sometimes there are too cell type that is equivalent to ESCs is transient and differ- many parameters to troubleshoot but we still have to try entiates quite quickly, which of course, is what is required to approach things in a systematic manner. You need to developmentally. look at your data critically and always be rational; one reason people can fail is because they don’t always look Have you had any ‘eureka’ moments, for example, at the evidence carefully enough. When you are doing when you discovered the selenocysteine codon or the something and you get a setback, it’s easy to quit, but it’s transcription factor Nanog? important not to. Well obviously, luck is a big part of this. Before we cloned Nanog, we spent quite a bit of time trying to clone a What is the best science-related advice you ever cDNA encoding an activity from a conditioned medium received? that modified ESC growth. What we ended up cloning There are a number of them. Louis Pasteur said: “Chance was LIF, which everybody had known for over ten years favours the prepared mind”, which just means read, read, drives ESC self-renewal. We still don’t know how that read! And then when you find something odd, you’re plasmid got into the libraries. That was a wee bit of a prepared to make sense of it. I also like a quote from 7
Left: Ian with his wife and fellow FEATURES couldn’t have predicted at the beginning. At biologist Helen Wallace during a the very start, it felt like a great opportunity walk on Irvine beach, Ayrshire, to get up early in the morning and follow with the hills of Arran behind. Mark Twain’s advice – he said something about getting up at 5 am and starting by eating frogs – I think he meant do the ugliest thing that you have to do first, and you’ll feel better and be more productive. That worked for some time, but not for four months. One of the first things that we did was try to normalise our timetables so that we were meeting regularly. We couldn’t really do lab meetings, but we did journal clubs every week. And at 4 pm every Friday, we had a virtual happy hour to try and talk over what we’d achieved during the week and just interact socially. Then we began to come out of lockdown and people are now back in the lab part-time doing Mohammed Ali. I have a poster in my office with a picture experiments. Things are beginning to change. of him training, and it says “The fight is won or lost away from witnesses – behind the lines, in the gym, and out You were due to receive your Hooke Medal at the British there on the road, long before I dance under those lights.” Society for Cell Biology annual meeting in Paris. Unfortu- I think it’s important that people get this. Everybody nately, the meeting, like many others, was postponed, wants to succeed. There was a mock version of the whereas others have gone virtual. How do you see the Lady Gaga hit, a few years ago, out of Baylor University future of scientific conferences changing? (https://www.youtube.com/watch?v=Fl4L4M8m4d0) I was really looking forward to receiving the medal at about being stuck in a bad project. People want to have the Institut Pasteur, as you probably could tell! But I’m something interesting to say that means that they have looking forward to the meeting in spring in Bristol. I’m succeeded on a project – something they can talk about, actually organising a meeting that was due to run in Kyoto describe their fantastic findings at a conference and get in November, but we’ve had to postpone that until spring feedback on from the top people in the field. But to get 2022. We now have the opportunity to rethink how we there you need to work hard and you need to put in the do things, and one thing we will be doing is offering the hours when many other people won’t be there. People get speakers the chance to deliver their talks remotely, rather lucky, but it’s not all about luck, it’s about work. than travelling to the meeting. That’s as far as I’ve thought about it. But at [The University of ] Edinburgh, we’re What is the most important advice you would give to changing our teaching to an online format, and thinking someone about to start their own lab? about other ways that we can engage students. Hopefully, I think probably the best thing you can do is find a there might be some new ideas for us to take forward positive but critical and sympathetic mentor to talk things to meeting organisation in the future, as we have to find through with. That’s not something that everybody does. new ways to deliver an experience that is good for all the There are also networks of new PIs. Not long ago, I went participants. to an EMBO course on how to be a PI; maybe I should have done that a long time ago, but you can always learn Could you tell us an interesting fact about yourself that something. Most of the people there were just starting people wouldn’t know by looking at your CV? their labs. This is a great opportunity to get together with When I left school, I didn’t go to university straight away. people who are in the exact same position, leading to a I worked for three years in a local factory that made network of support that might help take people through amoxicillin, which is a semi-synthetic penicillin. I worked their earliest years. in a chemical plant in the first year as a lab technician. How are circumstances different now for early-career The goal of the plant was to separate a racemic mixture researchers compared with when you started your lab? of the D- and L-stereoisomers of p-hydroxyphenyl glycine, I think many things remain the same; the biggest differ- a synthetic amino acid. If you look at the β-lactam group ence in the research landscape now is our [UK’s] chang- in penicillin, there is an organic R group at the side. In ing relationship with Europe. We don’t know what is going order to get a broad- spectrum antibiotic, that R group is to happen with the European Research Council funding taken off and, in the case of amoxicillin, is replaced by the going forward. We don’t know about the Marie Curie post- D-form of p-hydroxyphenylglycine. The plant was the first doctoral fellowship scheme, which is a very prestigious industrial-scale processing plant on the planet, as far as fellowship programme run by Brussels; also the Erasmus I’m aware, that used this approach to separate out stere- mobility programme for much younger students. These oisomers into pure D- or L-forms. Pasteur had separated things are unknowns and may limit who we can bring to D- and L-tartaric acid crystals using a microscope. So the lab. I’ve had many more non-British than British peo- here I was doing something that connected Pasteur and ple in my lab, including a lot of Europeans. I think there Fleming. And that was quite something. I thought I was are going to be fewer Europeans in newly established labs just going to work in a factory! [in the UK] in the future, which is a shame. Ian Chambers was interviewed by Inês Cristo, Features How did you and your lab cope with the lockdown due & Reviews Editor at Journal of Cell Science. This piece to the SARS-CoV-2 pandemic? has been edited and condensed with approval from the There’s definitely been an element of fatigue that I interviewee. 8
Women in Cell Biology FEATURES Early Career Award Medal 2020: Yanlan Mao Yanlan Mao was awarded the Women in Cell Biology Early Career Award Medal 2020. This annual honour is awarded to an outstanding female cell biologist who has started her own group in the UK within the last 6 years. Yanlan graduated in Natural Sciences from the University of Cambridge, UK, followed by a PhD in developmental biology and genetics at the MRC Laboratory of Molecular Biology (MRC-LMB), Cambridge. During this time, she studied cell signalling and epithelial patterning in Drosophila, under the supervision of Matthew Freeman. For her postdoctoral research, Yanlan moved to the Cancer Research UK London Research Institute (now part of the Francis Crick Institute), to study the role of mechanical forces in the orientation of cell division and cell shape control in Nic Tapon’s laboratory. She established her own research group in 2014 at the MRC Laboratory for Molec- ular Cell Biology (MRC-LMCB), UCL, where she addresses the importance of tissue mechanics during development, homeostasis and repair. She was awarded a L’Oreal UNESCO Women in Science Fellowship and the Lister Institute Research Prize in 2018. In 2019, she was award- ed the Biophysical Society Early Career Award in Mechanobiology and also became part of the EMBO Young Investigator Programme. What inspired you to become a scientist? Maybe that’s why I was drawn to biology; it was more of I think probably two things. First, as a child, I was always an unknown world, with more to be discovered. I really really interested in patterns in nature, such as the ones wanted to combine biology with maths, at some point in you find in leaves, flower petals or shells. I was always my career. In a way that’s what I’m doing now: mathe- fascinated by the diversity and how beautiful nature is, matical modelling of physical forces in biology, and still just by walking around and seeing the world. Second, tackling patterns, shapes and sizes of systems. someone that’s really influenced my career has been my dad. He’s a mathematician, and he’s very passionate Patterns can help deconstruct more complex systems. about his maths. As a result, I grew up always trying Does your interest in patterns come from a curiosity to to think of the world in a very mathematical way. He understand the basics? introduced me to physics, chemistry and maths very early Absolutely. Although I don’t exactly work on patterning on, as those were subjects he studied, but not biology. per se right now, it is still a part of some of my current 9
FEATURES work on tissue size and shape. The biophysics aspect gether with a common vision or a common goal to answer is probably where the maths comes in; I want to break the big question. Then it needs nurturing, just like in any things down into simpler problems or first principles, and collaboration. You have to be reliable and keep commu- try to understand, in as simple a way as possible, how nication going, especially if it’s long distance, because shapes and patterns form and how sizes develop. My that momentum has to be kept. That’s very hard. I’ve had PhD was in genetics; very hardcore, traditional biology, collaborations where you have that initial conversation which was great to train me as a biologist, scientist and and then nothing really happens. Everyone has different experimentalist. I think maths really helps to deconstruct priorities, different interests, but you can’t be shy. If that things. We can’t possibly understand all of biology. The collaboration is really important, you’ve just got to keep important message that I always give to people is that nudging them, keep emailing them, because you might trying to mathematically model something isn’t about not be their priority. As with many things, if you really creating the perfect cell or the perfect fly; if you can get a want something, you just have to keep trying. We honestly perfect model then you already understand everything, so don’t mind getting multiple emails. Well, to some extent! there’s no point in making the model. You need to convert the problem into simple components and understand Is this a quality that you also encourage in your PhD its basic core. Maybe it’s just three interactions or four students? proteins. Is that sufficient to already give you 99% of Yes, perseverance. At all levels, you’ve got to persevere. the behaviour of a system? If so, then that already helps Don’t be shy about annoying someone. It just shows you understand a lot about the system. It’s the logic of you’re passionate about something, and that you really breaking things down and putting things back together, care about it. I think most busy PIs wouldn’t mind that. but through simplification. Another piece of advice is to work smartly. I just had a conversation with my students about how, in some labs, So how did biophysics become the main aspect of your you have to work 18 hours a day, constantly pipetting. research interests and your current work? It’s true that more work means more outcomes, but smart I guess I got more into physical modelling because of my work is the important aspect. I stopped working weekends postdoc. A year before I started my postdoc, a beautiful quite early on in my career. I worked very hard during the paper was published from the lab of the late Suzanne week, when necessary. I’d be the first to open the lab and Eaton and Frank Jülicher on generating a vertex model, I’d leave on the last tube train. I also knew that I couldn’t a mechanical model of epithelial development. At the maintain that rhythm consistently, because I would just time, I felt this was the perfect kind of model for us to burn out. It’s a marathon, not a sprint. But that meant understand [Drosophila] wing shape. I actually learnt how smart working and designing my experiments properly. I to code by generating and adapting that model. Despite can see that students sometimes feel the pressure to con- my background in maths and physics, I hadn’t learnt any stantly work, but you don’t have to if you work smartly. computer programming, which is a huge problem these With every experiment you do, you should ask yourself, days. That was what got me into biophysics, because the ‘what was the point of that, what was the purpose, what model was very much a physical model of tissues grow- was the question, what was the hypothesis?’, so you don’t ing. To explore it, I had to learn biophysical experimental waste your time. At the beginning there is exploration and skills in order to test the predictions from the model freedom, but hopefully you should quickly become more and hypotheses, as well as generate new ideas with a targeted. Being selective and smart about what you do is biophysical spin. But I always linked back to my back- really important. And this also requires reading enough ground in genetics and signalling. In a way, that’s what to know your field, to help you know what is a smart I’m doing now in the lab – trying to combine the genetics experiment. It’s your job as a scientist to learn to manage and biology with mathematical and physical analyses to that, so you can design experiments that have the highest understand how changes in size, shape and form occur. chance of giving you something interesting. After all, you Thinking back now, I’m not sure if it was an active and have a finite period of time and you can’t do everything. conscious decision. Maybe it was a lucky accident, this semi-conscious decision of moving into the field of tissue What challenges did you face when you started your mechanics. First of all, I think I was very driven by the own lab? core question, which is tissue size and shape control – The main one was probably hiring, and also learning to let growth control. You need forces to move something. It’s go. Someone said to me once that you’re only as good as fundamental. Embryologists a century ago already knew your best postdoc or student. You rely on the staff you’ve that, even before molecular biology and genomics were recruited to do the core of the work, to generate the data available. Actually, they were doing what we’re doing and to push your ideas. But hiring is much easier said now, but just in a less technically advanced way. By the than done. How do you judge someone after a 30-minute end of my postdoc, the ‘renaissance’ of cell and tissue interview, or even a day of interview? I’ve been saying mechanics really helped me define my focus. I was still this to postdocs about to start their own labs: if you in a fairly niche field and I could create my own little area know someone good, try to poach them if they’re willing. of expertise. Since then, the field has increased more and Honestly, that’s what I did! I offered a job to my first post- more. People are starting to recognise and appreciate doc before I had my own job secured [laughs]. We still biophysics and mechanics again. joke about that. I’ve always said people in my lab don’t work for me, they work with me. That’s really important. Biophysics is an interdisciplinary field. What is your Once you hire well, trust the people in your lab to do their advice on establishing good collaborations? part of the teamwork. It’s important to learn to delegate Great collaborations take initiative to make that initial and to let go. When I went on my first maternity leave, connection so that you form a link. The good ones I’ve had which was about a year after starting my lab, I learned have always been where the two groups have different that I could let go for a bit. I wasn’t completely hands skills. For me, that’s the whole point – slightly different off, but it meant that the students and postdocs didn’t skills and different backgrounds, and then you come to- come running to me immediately with a question – they’d 10
FEATURES solve it themselves hiring people smarter than you.’ He really meant people and, most of the who have different knowledge and skills from you. He time, they would said not to be scared of that because you will learn from be fine. I think that each other. That really has shaped how I recruit people. I really forced me to hire people from all different fields. There’s no way I could learn that it’s okay be as good as the person doing the modelling, but that’s to step back. If you fine. If I were scared of hiring them, then that part of the trust them then, lab would never happen. Let the experts be the experts more often than not, in their own mini- fields. I’m completely comfortable with you realise they will the fact that I can’t possibly be the expert in everything. learn faster, they will But hopefully, I’ve had the years of experience and guid- own their projects ance to know how to point my staff in the right direction. and take them to Together, we work as a team to really complement each places that you other, and I’m constantly learning from my team (and vice probably wouldn’t versa, I hope). And that has been super exciting. have initially thought about. Give them How did you and your lab cope with the lockdown due space and freedom to the SARS-CoV-2 pandemic? to develop as unique We had ten days to plan. We had to get all our flies ready scientists; you don’t and flip them onto fresh food so that they’d be okay for want a whole lab of at least a month, because we honestly thought it would ‘mini-mes’ [laughs]! just be a few weeks; we never thought it would go on for That’s when science four months. When the lockdown did happen, though, gets exciting. we were okay to stay at home for a while. Everything was then Zoom based. We continued our lab meetings once a How are the chal- week, and everyone had their own tasks to do at home. lenges that you’re Most of them still had data to analyse. We’re a quantita- facing now different? tive lab, so we can analyse data to death! They have also A huge challenge been writing PhD theses, papers, proposals or reviews. It I had recently was was a matter of every person thinking strategically about to find bridging or what they can do that will help them in the future and extension money to save them time when we do go back. We also have Zoom Above: Keeping the kids give students and postdocs enough time to finish their socials and Zoom coffee breaks, just to keep spirits up. I entertained during lockdown: papers properly and get them published. When everyone’s think the hardest thing was keeping everyone’s motiva- learning how to cook and bake money is starting to disappear, but the projects haven’t tion going, especially some of the students and postdocs lots of new things together. finished yet, what do I do? Do I make them redundant? who are living on their own; it’s very isolating. So I Who will finish those projects? A person finishing some- would check in on them and make sure that they were one else’s paper always takes longer. Most of the time, ok, but also give them their space and not push them studentships are three years. That’s not really enough now too much at the beginning. I said to them that physical to finish. And postdoc fellowships are two years! There’s and mental health are the most important things, and if no way. Most of our papers weren’t published until about you don’t have those, you can’t do science. More or less, five years in, when you include the revision process. people are still making good use of their time and being Finding the money to extend people’s time in the lab was productive. Although we are really running out of things a huge challenge, as there are not many ‘flexi-grants’ to do [laughs]! After all, we are experimentalists, and we out there, even though it’s the most efficient use of the need to generate experimental data. Luckily, our institute money: the students and postdocs can finish and leave was one of the first selected as a pilot institute to open, with publications to help them find good postdoc or PI po- so there has been a lot of amazing work to get that ready. sitions. Very fortunately I got the Lister Prize, which saved Hopefully, we can start getting new data again soon. my lab, because without it I would have had to close pretty much the whole lab down – all those 2019 papers You have been quarantined at home with your husband might have still been sitting on the bench waiting to be and two children. Recently, a US-based study came out published. But I was able to use that prize money flexibly that suggests that female PIs have been less productive, to bridge a lot of the postdocs so they could stay and posting fewer preprints and applying for fewer grants, publish. I think it’s important to help the community by during this pandemic. What are your thoughts on this? creating more of these ‘flexi-grants’ or extensions, which It’s probably true. My husband’s great and we try to share would really make the initial investment into students and everything, but for example, I have a one-year-old and I’m postdocs so much more worthwhile. More and more, the the only one who can do some of the things needed. My funding timescale doesn’t match the time it takes to pub- husband and I basically work two-and-a-half days each, lish exciting stories, especially in biology and especially but I have maybe five hours per day, broken up by lunch for those starting labs. The funding bodies haven’t really time, nap time, dinner time and bath time, rather than full taken this into account. days, to do anything, whereas the days that my husband works, he really works the whole day. Despite our best What advice did you receive that was really important effort to achieve equality in the household, there are still for your transition to a PI? natural imbalances. I can just about keep the lab going, Besides hiring the right people, another piece of advice I but I haven’t been able to think enough to write a new got was from someone who wasn’t my direct advisor but grant, even though I should. Yes, we finished papers, but a scientist I really admire. He said something that really most of them have been papers that were already under stuck with me when I was a postdoc: ‘Don’t be scared of revision. The brain needs continuity and time to start 11
FEATURES writing from zero, and I just haven’t been able to do that Could you tell us an interesting fact about yourself that Yanlan Mao was interviewed with an hour or two here or there. My priority has been to people wouldn’t know by looking at your CV? by Inês Cristo, Features & make sure that everyone else in the lab is fine and happy. I’m actually quite a good ballroom dancer. Only at confer- Reviews Editor at Journal of Basically, it’s like another maternity leave for me. I’ve only ence parties do you see that appearing. I was on the Cam- Cell Science. This piece has been back in the lab since September, after my second bridge Dancesport team for two years; I was a beginner, but been edited and condensed child, and now I’m on ‘leave’ again! It’s definitely a huge doing competitive dancing meant I improved fairly quickly. with approval from the hit. It’s hard to even quantify that. I just had to accept the That was really fun. I started that during my PhD because interviewee. fact that I was going to be less productive. It’s a matter I needed something new to do. A lot of evenings I would of adapting and taking on the right attitude. That’s also leave the lab at 6 p.m. for my dance training, and I’d be at something really important in science. You can always competitions on the weekends. That really made me more see things in a more positive way and then embrace it, productive in the lab. And ballroom dancing is fun. and enjoy it. I have enjoyed spending more time with my children. That’s been awesome and has kept me sane. So let’s hope the conferences come back so we get to Honestly though, the first day I was at home with my two see your ballroom skills! kids full time, I thought, ‘I can’t do this!’ Then, once you Yes, I miss the real conferences and the conference settle into a new routine, time goes very quickly. parties! BSCB PhD Award – Inaugural Raff Medal Winner 2021: Flora Paldi The BSCB PhD Award – Raff Medal was established in 2020 to recognise BSCB PhD students who have made outstanding contributions to UK/Ire- land cell biology. The medal has been named after Professor Martin Raff who was the president of BSCB from 1992-1995. Martin was instrumental in setting up and running the first 4-year PhD graduate programme in Mo- lecular Cell Biology at the MRC Laboratory for Molecular Cell Biology (LMCB) at UCL. F lora obtained her BSc with Honours in Molecular Genetics from the University of Edinburgh in 2015. In the same year, she joined the Wellcome 4-year PhD During her PhD, Flora communicated her findings to national and international conferences where her presentations were singled out on multiple occasions. Programme in Cell Biology, University of Edinburgh. Her work was recently published in Nature and creat- Following a rotation year, she started her PhD in the lab of ed excitement in the field because it demonstrated a Professor Adele Marston at the Wellcome Centre for Cell direct, causal relationship between the 3-dimensional Biology. organisation of a specific domain with cellular function. Flora’s PhD focused on the role of pericentromeric chro- Besides research, Flora was also an active member of mosome structure in mitotic chromosome segregation. the scientific co mmunity, participating in peer support, Using budding yeast as a model, her work deciphered student representation, public engagement and the organ- the chromosomal structure in which kinetochores are isation of local scientific events. Currently, she is working embedded in mitotic metaphase, and the restructuring as a postdoc in the lab of Giacomo Cavalli (IGH-CNRS that is caused by microtubule attachment. She showed Montpellier, France), where she continues to explore the that the ring-shaped protein complex cohesin, together relationship between 3-dimensional genome organisation with centromere-flanking convergent gene pairs structure and transcription. pericentromeres. As the resulting structure promotes You can follow Flora @flora_paldi on Twitter. The med- accurate chromosome segregation, this constitutes an im- al will be awarded at a virtual medal lecture during the portant conceptual advancement, establishing the linear next joint BSCB/Biochemical Society meeting, Dynamic arrangement of transcriptional units as a novel parameter Cell IV Dynamic Cell IV which will be held on 14-19 governing genome transmission. March 2021. 12
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