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Meet Dr Hayley Sharpe, tenured group leader

Dr Hayley Sharpe joined the Institute as a Signalling programme group leader in 2019. In 2020 she became an EMBO young investigator, received a Lister Research Prize fellowship and an extension to her Sir Henry Dale fellowship. This year, Hayley was awarded tenure. In this profile Hayley reflects on what motivates her as a scientist and group leader, hopes for her field, and time at the Institute so far.

When did you start thinking you’d like to be a scientist?

I always preferred doing science at school. It was always my favourite subject and so I picked all science subjects even taking PE GCSE because it included biology. I always wanted to do science, I just didn't know what you could do with it. I didn't have an idea of what a scientific career would look like at all, I just knew I was interested in biology and chemistry and maths. I had an inspiring biology teacher- she went back and forth between industry and teaching so she had a lot of enthusiasm, perspective and, importantly, a sense of humour.

I studied biochemistry at Bath University where you get to do a lot of practical science, which I always enjoyed. I worked in labs in the US for two summers which helped me gain experience in real life academic lab work. I applied to the LMB for my PhD because I’d asked for advice on membrane trafficking labs, and Sean Munro was very well regarded as a great scientist and mentor. At the time I didn’t really know what it meant to win the Nobel Prize. You know, I was very naive. You just don't have awareness of that type of thing if you’re not exposed to it growing up.

What is your favourite part of being a scientist?

I love digging into a problem and solving it. That's how I set up my lab - I went in a different direction from what I’d worked on in my PhD or postdoc. This gave me an opportunity to identify a black box and set out the questions to ask to try and figure things out. And I think we have! It’s really satisfying, getting data where you don't really know what that means straightaway and being able to just think it through, think about the logic and come up with a model that we can then try and break, or confirm.

I also get a lot of pleasure from interacting with other scientists. It’s a pleasure to be around very enthusiastic people. On top of it all, just learning about how the world works from a biological perspective is amazing.

For anyone considering a career in academic science, I think it’s also fair to say that it has its challenges so it’s important to think about whether it’s the right career for you. I did this through my undergraduate placements and also by learning from people at a later career stage to me. My advice would be that you must find some joy from it. If you have that, you can navigate everything else.

What is your current research focus?

My lab aims to understand enzymes called protein tyrosine phosphatases (PTPs), which are key parts of the cells’ signalling pathways. They’re a bit of an enigma in that we don’t have a really accurate picture of how they work. We’re trying to piece together the mechanisms of how they functionally work to understand their roles in maintaining health, as well as how they contribute to disease and ageing. But more recently, we've got into how they work with kinases. I don’t think you can study just one thing in isolation. Overall, we're particularly interested in how the cellular microenvironment and its mechanical properties impact on signalling outcomes for these enzymes.

What does your research mean for healthy ageing and disease?

The receptor tyrosine phosphatases are known to be involved in several different areas of our biology, from immune cell signalling to blood vessel development to cell-cell adhesion, and dysregulation in cell signalling is a feature of ageing and disease.

We know from our research and that of others that changing the physical properties of the cells’ environment changes their behaviour, so it’s possible to think about how we can manipulate disease processes based on that.  We know with ageing that collagen declines, and you have all these different changes in mechanical properties, and that is going to impact on signalling. Trying to understand these causes and effects will open up avenues of approaches for translational development. 

Where do you see your field going?

Researchers have been really focused on the catalytic function of PTPs, but we're finding lots of non-catalytic functions that can then be controlled by the redox environment (the level of reactive oxygen species in the cell).

I think the next important step is to convince people that redox signalling really should be part of the mainstream way we're thinking about cell communication. Hydrogen peroxide is a cellular secondary messenger, but isn’t part of everyday thinking in the field yet. Part of the challenge is measuring it, so we’re using tools developed by others to see it in cells. We think it is so fundamental to understanding PTPs and tyrosine kinases that we can’t ignore it.

What is it like to be a group leader?

I have found that you get increasingly distant from the lab. In the beginning I was at the bench, then after the pandemic and with the lab growing, I was more at my desk. Overall, I think a happy lab is a productive lab. When you put a grant together, the most expensive part of your grant is people, so they should be valued. I understand that an academic career isn’t for everyone, however, becoming an independent scientist is important for lots of careers.

In terms of managing people, I see my role as helping people grow into independent scientists, or wherever they want to be in the end. Hopefully that means your team can succeed with whatever path they want to choose. I was once told on a leadership course that my personality type is unusual for academia. To me, empathy is vitally important. If you can understand where someone else is coming from, you're much better able to manage them because you can have their interests at heart, and then they're going to be more intrinsically motivated.

Can you tell us a bit about your team?

I try to encourage a team ethos and it’s important to demonstrate that in practice. As a new lab, when we were publishing our first paper everyone chipped in and so everyone was on that paper. We still have that attitude of supporting each other and giving credit to each other, the nice thing about academia is that you can credit people for their help. We work really well together, and in the end, the lab success is everyone's success! I’m also lucky that some of them are great bakers!

As Chair of the Institute’s equity4success steering group, how do you feel about the way forward for underrepresented groups in science?

I feel very strongly that we should recognise the fact that there is not a level playing field and that to make progress we should look at actions that are not applied as a blanket but instead are adapted to the different needs of different people. I am pleased to be able to be an advocate for women in science at the Institute and beyond, and see everyone involved in making change.

What are your highlights of your time at the Institute so far?

It’s hard to pick really, when my first student defended their thesis during lockdown we had an online Zoom celebration afterwards – I sent everyone a bottle of something to celebrate (alcoholic or not). We still made the best of it, but it's not quite the same, it was just nice to be back. There was a ‘Blue Skies’ online retreat organised by the tenure track group leaders where everyone showcased their science but also everyone was really getting into what it means to be in this Institute. I thought that was that was a really nice thing to be a part of.

Career snapshot:

Dr Hayley Sharpe gained her PhD with Dr Sean Munro FRS at the MRC Laboratory of Molecular Biology in Cambridge investigating how transmembrane proteins negotiate the membranes of the secretory pathway. She then moved on to study clinical resistance mechanisms to a Hedgehog pathway inhibitor in skin cancer as a postdoctoral researcher at Genentech, USA, from 2011. In 2016 she started her lab at the Cambridge Institute for Medical Research (CIMR) after obtaining a Wellcome/Royal Society Sir Henry Dale fellowship to focus on cell signalling by receptor tyrosine phosphatases. She joined the Institute in 2019, became an EMBO Young Investigator in 2020 and also received Lister Research Prize fellowship in 2020.