Cell scientist to watch – Alexis Barr

Alexis Barr

Congratulations on winning the 2024 BSCB Women in Cell Biology Early Career Award Medal; what does winning this award mean to you?

I was very touched to receive this award because I've always had a really good relationship with the British Society for Cell Biology (BSCB). As a masters student, the first conference I ever attended was the joint BSCB/BSDB spring meeting in Warwick in 2005. It was absolutely fantastic, and it made me realize that working in science would be a worthy and fun career. Since then, I have always admired the BSCB and all the work they do. I was a postdoc representative on the BSCB committee many years ago and got to see from the inside how hard the committee works for the cell biology community. Receiving this medal from the BSCB was really an honour, and the fact that it is voted for by peers is very meaningful for me.

What inspired you to become a scientist?

I always liked science at school, but I never really understood that I could do science for a living. No one I knew was a scientist. The only career involving science that I knew about was forensic science, but I didn't want to do that because I am very squeamish. Even so, I decided to go to university and study Biological Sciences because biology and chemistry were my favourite subjects. During my second year of university, my Director of Studies suggested that I do a summer placement in a lab to gain research experience and see if I liked it. I went to work at the MRC Laboratory of Molecular Biology (LMB) in Cambridge with Andrew Leslie, a fantastic structural biologist. It was then that I realised working in a lab as a research scientist was not only possible but could also be a lot of fun. I think that was the turning point when I knew I wanted to become a scientist.

What initially drew you towards studying cell division and centrosomes for your PhD?

During my master's programme, we had very memorable and inspiring lectures on the cell cycle from Jon Pines and Frank Uhlmann. I thought the cell cycle was fascinating and so I chose to do my master's project in Jordan Raff's lab, who was then at the Gurdon Institute in Cambridge. It was in his lab that I first started working with Fanni Gergely, who was then a postdoc. Fanni was teaching me how to find mitotic cells that we had immunostained for microtubules, centrosomes and DNA under the microscope. I remember the first time that I found one. I thought it was just beautiful, and I wanted to understand how this magnificent spindle structure was assembled, and how cells align and segregate their DNA into two new cells. When Fanni was leaving Jordan's lab to set up her own team, she asked me if I wanted to be a PhD student with her. I jumped at that chance and that's how I got hooked on the cell cycle.

For your postdoctoral research, you moved to Chris Bakal's lab at the Institute of Cancer Research (ICR) in London. What did you work on there?

When I was finishing my PhD, I realised that I wanted to continue working on the cell cycle using imaging to study this process, because being able to see how things work is very powerful in understanding cell systems. However, I wanted to move away from mitosis and cell division and do something a bit different. At that time, there weren't so many people studying how mammalian cells enter the cell cycle; specifically, the process of how a cell goes from quiescence into the process of DNA replication in S phase to start proliferating. I wanted to work in that space using single-cell imaging, which had been such a useful tool during my PhD in studying mitosis. I also wanted to take a more systems-level approach to studying cell cycle control. I had seen Chris give a talk about using approaches like high-content, high-throughput imaging, screens and computational modelling to understand cell shape. I emailed him to ask if he was taking on any postdocs, and luckily, he was. I was very fortunate in that Chris was a very supportive supervisor and gave me the freedom to pursue my own project using the tools available in his lab. It was a fantastic opportunity: with Chris' encouragement, advice and support, I could build up my own research programme, looking at how cells enter the cell cycle using these systems-level approaches.

While you were at the ICR you established a strong collaboration with Bela Novak, a mathematical modeller at the University of Oxford. What is your advice on establishing good collaborations as an early career researcher?

Don't be afraid to email people you'd like to collaborate with, even if they're much more senior than you. I had not met Bela before, but I knew that he had done cell cycle modelling in other organisms and that his approach would be extremely powerful for understanding how human cells enter the cell cycle. I emailed him, explained what I was doing and asked if he would be interested in potentially collaborating. He invited me to give a talk, during which I was really grilled by Bela and his group, but it was a fantastic experience and really useful. It made me realise that this would be a really fun collaboration since modellers think about scientific problems completely differently to the way that I do, and they made me think about this project in a completely new way.

Having collaborated with many people over the course of my career, I think there are a few things to bear in mind: it's really important that your collaborators are also invested and interested in answering the research question. Somebody could have a really useful and cool technique, but if they're not that interested in your research question, it can end up being quite difficult to keep them engaged in the project. Another key point is that, for example in Bela's case, there was somebody from his team who worked directly with me and with who I was in almost daily email contact. It's important to ensure that there is someone on both teams engaged with and committed to the project. I also think it's really important to get along well with the people you're collaborating with, because if you don't find them easy to talk to, it's going to be a real struggle. I'm fortunate that I find it very easy to talk to all of my collaborators. We can challenge each other, knowing that it's coming from a place of good intentions, and it's fun to collaborate with them – it's never a chore. I highly recommend collaborating because having different people with different ways of thinking always brings something new to a project.

In 2018, you started your own lab at the Institute of Clinical Sciences, Imperial College London. What challenges did you face when starting your own lab that you didn't expect?

I started my lab in September 2018 and then obviously, a year and a half later, the COVID-19 pandemic hit. COVID led to many disruptions that we couldn't have anticipated and, as a result, I always find it hard to untangle the difficulties associated with the COVID pandemic with the normal challenges of establishing a group. One of the things I probably hadn't truly appreciated before I started is that when you go from being a postdoc to running a lab, you go from being part of the team to leading the team. You have to shift your mindset because you are taking on a different role – a leadership and management role – and that can be quite isolating. I was very lucky because when I started at Imperial, I had a number of colleagues who started their labs around the same time, so we had an instant peer network. I didn't feel isolated because I had great colleagues who became good friends as well. I think another challenge is that you leave a postdoctoral role where you have become super productive over the years and then move to a new place where you have to build a new lab from scratch which takes time to run efficiently.

How are the challenges that you're facing now different?

Whenever you bring someone new into the team, one of the biggest challenges is that you have to find the best person for the role, but also ensure they will get along with the team. We have really good team morale, with lots of different personalities but where everyone gets along very well and it's vital to maintain that environment. Another challenge I have, now that I'm approaching 6 years of running the lab, is preparing to apply for new funding. I am very conscious that the decisions I make influence not just my career, but also the careers of my team members. Being responsible for other people's careers now as well as my own can be quite a weight of responsibility.

What are the main questions your lab is currently trying to answer?

Our research is centred on understanding how human cells enter and exit the cell cycle. We are interested in how cells transition between quiescence – where cells are resting or dormant – and proliferation. This process is crucial during development and tissue homeostasis, ensuring cells strike the right balance between proliferation and quiescence at the appropriate times. Dysregulation of this balance can lead to cancer. Using a mechanistic cell biology approach, we study the regulation of cyclin–CDK complexes and how they control the transition between quiescence and proliferation. We want to use this knowledge to optimize the use of cell cycle-targeting drugs in cancer treatment by identifying the populations of patients that would be most responsive to drugs being tested in current clinical trials or those that are already used in cancer treatment. We also want to understand the difference between quiescence, a reversible cell cycle arrest, and senescence, which is a permanent cell cycle arrest. These terms are sometimes used interchangeably, as we don't really understand how quiescent cells maintain their potential for proliferation and what prevents them from becoming senescent. Therefore, our goal is to uncover the mechanisms through which quiescent cells retain proliferative potential. Additionally, we want to identify reliable markers that can distinguish quiescent cells from senescent ones. This distinction is very important because quiescent cancer cells can ‘reawaken’, leading to tumour relapse, while senescent cells cannot re-enter the cell cycle.

Are you still doing experiments yourself?

No, I stopped doing experiments around October last year. Up until that point, I was still spending ∼40% of my time on experiments. However, I've now reached a point where, although I was initially hesitant to give up bench work because I enjoy it so much, my time is better spent writing manuscripts, applying for grants, attending conferences and discussing our work with others. I currently can't see when or if I will ever return to doing bench work. Sometimes, around Christmas, I will feed cells for lab members while they are away, but that's currently the extent of my lab work!

You volunteer for the Social Mobility Foundation, mentoring pre-university students. Tell us more about this role.

The Social Mobility Foundation mentorship programme is for UK students who are in their first year of Sixth Form, pursuing A-levels (16–18 years old), and aspiring to attend university. These students come from socioeconomically disadvantaged backgrounds. They are on track to achieve good grades in their A-levels and attend university. No one in their family has attended university before, leaving the students unfamiliar with how the university system and application process work. Additionally, depending on their school, they may not receive adequate support.

As a mentor, I help these students navigate the university system, including understanding how to choose a university and a course. I also advise on work experience they can gain before attending university. I help them in writing their personal statements and better framing their motivations for wanting to attend university. I'm still in touch with some of the students that I first mentored, which is always very nice. This type of mentorship is important because, as academics, we have access to a wealth of information that these students lack. Simple guidance can really help them navigate the system. I sympathise with this, because my cousins and I were the first generation of our family to attend university, and we didn't have this sort of information handed down to us. Fortunately, our schools were supportive, but for those without such support, external guidance is essential. I am very proud of the achievements of the students I have mentored.

What is your own approach to mentorship as a group leader?

In terms of my mentorship style, I first and foremost try to lead by example. When mentoring people, I recognize that everyone is different and has unique needs. For example, with the people in my lab, I have long conversations about what they want out of their career and how I can best help them to achieve that. We have these conversations at least a couple of times a year, to see if their ideas have changed. I also receive a high number of requests to mentor people, particularly women postdocs, because I have experience balancing having children during my postdoc years and now as a team leader. I share my experiences, including what did and didn't work well and what I would have done differently. I also encourage people in my lab to talk to people about their projects, even very early on. In my opinion, this is how science should be – an open discourse where people share results early to advance our collective understanding. Not hiding everything away until the paper is accepted. It's also a huge benefit to people in the lab as they can go to conferences throughout their time in the lab, become known for their work and form collaborations.

Together with Dr Michelle Percharde and Dr Toby Warnecke, you have been instrumental in establishing a Roving Researcher scheme at the MRC-LMS. Can you tell us more about this scheme and why it is so important?

This is a scheme that provides research cover for postdocs going on long-term leave, which is anything more than 3 months. So far, our Roving Researcher scheme has mainly covered maternity leave, but they can also cover long-term sick leave. We wanted to implement this because when a researcher goes on leave, their project often just stops. This can be extremely stressful for a postdoc. We wanted to alleviate that stress so that people can enjoy their maternity leave or, in the case of sick leave, relax and recuperate.

The Babraham Institute started a Roving Researcher scheme a few years ago, and they offered us a lot of help when setting up our system. A Roving Researcher, who is employed through the scheme, works between two or three labs to cover for postdocs on leave. This model is working well because this person understands the institute thoroughly, knows how everything works and can work on multiple projects simultaneously. The researcher on leave can decide whether they want to stay engaged with the research while they're away – whether they want to meet with the Roving Researcher to discuss progress during their leave – or step back and delegate that to someone else in the lab. That decision is entirely up to them. This scheme has been hugely successful, and our Roving Researcher is now a permanent position at the LMS. For the Roving Researchers themselves, it's a really exciting role because they are constantly learning new techniques, undergoing training and meeting new people. More institutions are now starting to implement their own Roving Researcher programmes.

Can you give me suggestions of how to improve the lives of scientists that are parents?

One huge advantage of being a scientist parent, compared to some of my friends who are parents and in other careers, is the flexibility. For example, today is my son's 10th birthday, so I'm going to leave early to pick him up from school and celebrate with him. I'll probably have to do some work later on in the day, but that's fine, it's just a busy grant-writing period right now. However, there are still improvements that can be made. One of the biggest issues is the cost of childcare. I had both of my children while I was a postdoc, and for one year, they were both in full-time nursery. The cost of childcare for that year was more than my salary. Some people said I was crazy to go back to work during that time, but I love my job and wanted to advance my career. We were fortunate enough that we could take that financial hit for a year, but you can see why that cost would stop people from returning to work. We need much, much cheaper childcare. Whether this should come from the government or universities, I'm not sure, but it would be a huge help.

Another issue I advocate for, and discuss often with Michelle Percharde, is encouraging more partners to take formal parental leave. If more women were able to return to work while their partners took time off to care for their children, I think it would help immensely with the gender imbalance in the senior positions in academia. My husband took 6 months off with each of our children. I took the first 6 months and he took the second 6 months. I always encourage others to do this, because it would greatly support women in science.

Finally, could you tell us an interesting fact about yourself that people wouldn't know by looking at your CV?

People might not know from my CV – but they probably know if they follow me on Twitter/X – that I'm a huge football fan. I grew up supporting Barnsley FC and used to have a season ticket. I attended every home match and many away matches until I went to university. I also played football at university and continued to play until recently when I ruptured my anterior cruciate ligament. So yes, I'm a huge football fan!

Alexis Barr was interviewed by Sara Morais da Silva, Reviews Editor for Journal of Cell Science. This piece has been edited and condensed with approval from the interviewee.