First Paper As PI: Hayley Sharpe

Changing fields increases your chances of establishing your own research niche.

After completing her PhD at the University of Cambridge Hayley Sharpe crossed the Atlantic to do a postdoc at Genentech. Five years later she returned to the UK to set up her own lab studying phosphatases at the Cambridge Institute for Medical Research. Now in the process of moving her lab to the Babraham Institute in Cambridge, her first paper as PI was published in eLife in March.

Hayley Sharpe. Image credit: Robert Garrett

How do you describe your research to your friends and family?

With arm movements and scribbled diagrams! I explain that the cells in our body use proteins on their surface to talk to each other and act in concert to enable tissues and organs to work properly. The proteins my group works on – phosphatases – are receptors that can sense changes in the neighbourhood of a cell, and then relay this information to other proteins inside the cell to influence its behaviour: for example, the cell might move or stick to another cell. Knowing how these proteins work could improve our basic understanding of diseases such as cancer.

Why did you move into industry for your postdoc?

After much soul searching at the end of my PhD, I knew I wanted to do a postdoc. I was in the fortunate position of being able to move internationally, and I wanted to find a lab where I could learn a new area of biology, particularly in the area of cell signalling. I knew another student who had gone to Genentech in California to do a postdoc – and then a job opening came up there. At my interview I got a tingly feeling. I was surrounded by people who were really excited about science and asked insightful questions about my work, despite it being quite distant from their research areas. I had no hesitation in taking up a position there.

What differences did you notice between academia and industry?

Overall, most discovery still happens in academia but industry can translate those findings much more effectively to impact on patients. The resources and scale of operation in industry are much larger. Another difference is that entire teams are acknowledged for successes, whereas any acknowledgement in academia tends to focus on individuals.

Why did you move back into academic science?

Academia never left my mind as an option, but at first I was too scared to say it out loud as I worried about sounding presumptuous or arrogant. My postdoc was far from straightforward: I spent a few years on projects that did not yield anything publishable, despite hard work. Coming through that experience of effectively starting over in my postdoc built my confidence enough for me to admit that I wanted to run a lab. I was pleasantly surprised when people took me seriously.

Why did you change fields between your PhD, postdoc and PI positions?

I knew it would be important to establish a research niche, and I thought that it’s very hard to justify how you’re going to add something new if you just do what your supervisor did. You also learn so much by going into different areas or different environments. All fields can benefit from a new perspective – if we only stick with what we trained in we will not get very far.

Do you think you’ll change field again?

I think I’ve found my niche now. This is an area which I’m really excited about because phosphatases are massively understudied, but they’re clearly really important for health and disease. There’s potential to uncover new drug targets if we can learn more about the basic biology of phosphatases. Actually, that’s one thing that I learnt at Genentech: understanding how things work can help make better drugs.

How did you become a group leader?

In the end it took more than one and a half years from deciding to try to become a group leader to starting my lab. I thought that returning to the UK would be my best option because I did not know the US system. I then went on an information-gathering mission, Skyping with people who had recently become group leaders. That year I travelled to the UK for an event, and discovered that the Cambridge Institute for Medical Research were about to put out a call for Principal Investigators. With the institute’s support I was able to set up my lab with a Wellcome/Royal Society Sir Henry Dale Fellowship.

What was the biggest challenge you faced when setting up your lab?

Although I said changing field has its advantages, a major challenge for me has been getting established in a new area, without a former supervisor’s reputation to help. But I went out and networked as much as I could in the field, and reached out to people at meetings. This even led to a collaboration.

What do you enjoy the most about being a group leader?

Until you start it is hard to appreciate how many different tasks will fall on your plate, from managing and hiring people to writing appraisals to training people at the bench, before you even get to thinking about your science! Outside of the lab I also help run a graduate program within the Cambridge Cancer Centre, and deliver a lecture. I really enjoy this variety. It is such a pleasure to work with engaged and bright people every day, and it is very satisfying when your ideas pan out.

What kind of atmosphere do you try to encourage in the lab?

First and foremost, I want people to come to the lab who are excited about the science we are doing. I want the lab to be friendly, supportive and open. One of our most exciting recent results came from data that showed the opposite to what we had expected. I feel like if we didn’t have a nice open atmosphere those results may have been buried. I also make a point of admitting my mistakes – we’re all fallible, it is how you react and what you learn that is important.

How would you summarise what you show in your eLife paper?

The phosphatase we studied, PTPRK, had previously been implicated in cell adhesion and cancer. We were able to demonstrate that it dephosphorylates at least five substrate molecules, all of which are linked to cell adhesion. We think that changes in cell shape and the inability of PTPRK-deficient cells to correctly organise their internal skeleton might explain how PTPRK suppresses tumours.

How did you celebrate the paper being accepted?

As you only publish your first paper once, we celebrated twice! I took the lab out for dinner, then we had a celebration with all the Cambridge-based authors, which included sampling the first author’s favourite beer from a brewery in Yorkshire.

How do you hope your lab will develop?

Two days after the eLife paper was accepted I got a job offer. We’ll still be in Cambridge but we will be moving to the Babraham Institute next month, where there’s potentially even better scientific overlap. It’s also tenure track and comes with more funding, so it means I can immediately expand the lab. But otherwise nothing major will change – we’ll still aim to figure out the principles of signalling by tyrosine phosphatases in different model systems.

What advice do you have for people who are about to establish their own labs?

Get organised – I use online tools like Benchling, Trello and Google Calendar to run my life. Hire the right people, and care about your trainees – they are the most important part of the lab. And focus – we all have a million ideas but you will be judged on what you finish.

Hayley Sharpe CV

2019 – present: Tenure-track group leader, Babraham Institute, UK

2016 – 2019: Principal Investigator/Sir Henry Dale Fellow, Cambridge Institute for Medical Research, UK

2011 – 2016: Postdoctoral researcher, Genentech, USA

2010 – 2011: Postdoctoral researcher, Medical Research Council Laboratory of Molecular Biology (MRC LMB), UK

2006 – 2010: PhD in cell and molecular biology, MRC LMB, UK

2002 – 2006: MBiochem in biochemistry, University of Bath, UK