Originally planning to study medicine at university in Australia, Mekayla Storer fell in love with research while doing her undergraduate degree in Biomedical Sciences. Fast forward a few years, now at Cambridge, she is an early career group leader hoping to uncover the secrets behind regeneration. Why do deer grow back their antlers every year? How do salamanders re-grow entire limbs? What can we learn from animals (and plants!) about regeneration that can help us find better treatments for human disease?
“What is most exciting is that there’s not just one way of regenerating. If we can adopt mechanisms from other species, we could potentially use that as an inventive way to come up with better therapeutics. I’m really fascinated at the moment with how plants are able to regenerate. They’re crazy! Could we learn something from plants that could be applicable?”
Sparking an interest in regeneration. I first moved to Cambridge in 2007 to work as a Research Assistant at the Wellcome Sanger Institute. I had finished my degree in Australia and then spent two years travelling, which made it very clear to me that I really wanted to do research. At the Sanger Institute, I had the opportunity to explore this career a bit more and the natural next step for me was doing a PhD. As an international student, it’s more difficult to find studentships you can apply for, but I was lucky to get a place at the Centre for Genomic Regulation in Barcelona, Spain, which is where I spent the next 5 years. It was really a fantastic environment to study and work. I was surrounded by great minded people, and everyone was really social and helped each other out. It was a great experience for me and the setting close to the beach was definitely a plus! And that’s where my interest in regeneration began.
Skin cells, embryos and ageing. I worked in a lab that did research on ageing and senescence in the skin. Senescence is generally thought to be a pathological process. So, as you age, you have these cells that exit the cell cycle and just sit there. They can be any cell type. They sit there, but still secrete (produce and discharge) lots of factors and influence cells around them. In a normal process, senescent cells are usually cleared from the body. But, as we get older, these start to accumulate and because they secrete lots of things, they can affect the tissue around them. That’s how you get the signs of ageing, your muscles don’t work as well, your skin gets wrinkles.
We also studied embryos and looked at the developing limbs where we found these senescent cells also exist there and have a role in instructing the limb how to develop, but they’re cleared very efficiently. They do their job, and then get removed so they’re not detrimental. But in ageing, they tend to stay around, so it looks like ageing could be an overstimulation problem.
After finishing my PhD, I moved to Canada, where I stayed for another 5 years, working with Freda Miller and David Kaplan. I was involved in 2 different projects, one looking at the role of maternal infection in the development of the embryonic brain and the other one investigating finger tip (or ‘digit tip’) regeneration.
Why do finger tips grow back? Looking at the digit tip, we were trying to understand why, if you amputate or remove the very end of your finger, it grows back, but if you go beyond the nail and amputate further than that, it doesn’t. You get this sort of scar tissue. We wanted to understand how this process works and why can the end of the finger regenerate, but not the whole finger, nor a whole limb.
When you cut off the end of the finger and still have part of the nail, this very transient structure forms, which is full of regenerative progenitor cells. However, we didn’t know where they came from, nor what types of cells they could make. We went on to do a big study to characterise them and we found something truly fascinating.
We found that these regenerative progenitor cells come from many different tissues; they come from nerves, they come from bone, all these tissues that are at the site of the injury can contribute cells to help the repair process, and then these cells are able to go back and make the tissue they came from. Some of them are even more special and can make multiple types of different tissues as well. I find this incredibly cool!
Image on the left: Fully regenerated mouse digit after injury
We also know now that it’s not a case of simply having or not having these ‘special’ cells in certain areas of the body. Our research showed that cells from the skin, if placed in a regenerating digit tip, will also contribute to the regeneration process, and they could even become bone cells as well - this is really fun! It means that other cell types may have the potential, if you just give them the right cues, to support the regeneration process. Our thinking is that in the finger tip these regenerative cues are likely coming from the nail itself, secreting factors and making a regenerative environment possible.
Plants grow back, why not limbs? I’m very curiosity driven. I’m very interested in how different species have different methods to regenerate. And what excites me about that is that there’s not just one way of regenerating. If we can adopt mechanisms from other species, we could potentially use that as an inventive way to come up with better therapeutics. I’m really fascinated at the moment with how plants are able to regenerate. They’re crazy! Could we learn something from plants that could be applicable to human tissue?
Coming back to Cambridge. My move to Cambridge got delayed with the pandemic, but once I got here, with funding and intellectual and moral support from colleagues at the Cambridge Stem Cell Institute, things have progressed well and I am fortunate to have just been awarded a Career Development Award from the Wellcome Trust for the next 6 years. It means that we can now really focus on doing our research. It’s very exciting!
My team is now taking our regeneration research one step further, trying to work out what the regenerative differences are between species and what are those important environmental cues that support regeneration? We’re doing a lot of single cell RNA sequencing work to find out what genetic signals (known as transcripts) are being sent out in damaged tissue and how these genetic instructions change between a regenerative and non-regenerative environment. And we’re also combining it with a bit of tissue mechanics, because we know that it’s not just the chemical signals that a cell interprets, it’s also the physical environment that it’s in. Is that environment a little bit stiffer or is it softer and how does this relate back to the cell to tell it what to do and what to become?
So, it’s not just about growing fingers or limbs. Even more exciting is whether we can apply this to other parts of the body. Can we find ways to regenerate cartilage? Can we find a way to get rid of fibrosis (scar tissue)? In a lot of diseases, you get fibrotic scar tissue, such as cystic fibrosis, fatty-liver disease, even heart attacks. You get fibrotic tissue in your heart after infarction which makes regeneration really difficult. Could we get the heart to actually create a regenerative environment? This could mean incredible breakthroughs for a lot of diseases.
Cambridge is the perfect place to be doing research. I don’t think I’ve ever seen a parallel academic environment where there are so many really clever people who are so willing to collaborate and help colleagues out wherever they can. Everyone is incredibly busy, but extremely generous with their time.
The Research Themes in the School of Biological Sciences have been great for this. We’ve started working on this ‘Complex Tissue Regeneration’ Grand Challenge. It has been fantastic to spearhead this initiative and bring together a lot of different researchers from across the University, who you may not realise work in that area.
I’m also involved in the Early PI Network, which is group of over 50 Principal Investigators who have started their lab in Cambridge in the last five years. There are a lot of challenges for early group leaders and I think this network has been really fantastic in bringing people together to have collective experience on how we can actually address those kinds of challenges. I started attending meetings and ended up being one of the coordinators for the last year.
Students here are full of energy. I also enjoy interacting with undergraduate students a lot. I teach on a Part II (3rd year) course, shared between Zoology and Physiology, Development and Neuroscience. I’ve been doing lectures on limb development, understanding how the limb patterns and develops, and also a lecture on limb regeneration. Additionally, I supervise first year students at Fitzwilliam college on the biology of cells. Students have different perspectives, they are bright and full of energy. They ask very interesting questions. They have different perspectives, sometimes things I hadn’t thought about. I find this to be very valuable!
I see myself staying in Cambridge for a long time. The academic environment, the collaborative spirit, all the resources, it’s incredible. I feel very supported. When I got the news of my Fellowship from the Wellcome Trust and wanted to thank everyone for their support, I realised that I had a really long list of people to say thank you to, from colleagues in the Early PI Network, to professional staff in the School, to people I didn’t even know who helped me succeed.
“Cambridge is the perfect place to be in the sense that I don’t think I’ve ever seen a parallel academic environment, where there’s really clever people. But they’re also incredibly collaborative, people are willing to help you. Everyone is very busy, but extremely generous with their time.”
Mekayla Storer is a Career Development Fellow and Group Leader at the Wellcome – MRC Cambridge Stem Cell Institute and Department of Physiology, Development and Neuroscience. She is also a Theme Lead of the Reproduction, Development and Lifelong Health Research Theme in the School of Biological Sciences.