The tools to translate: An early career researcher perspective with Dr Wioleta Zelek

When studying a condition like dementia, we aim for our research to have a life-changing impact on people, often through the development of new treatments and technologies. There are still many hurdles from the early stages of discovery science to the clinic, but a better understanding of the translation process is a key part to help focus our aims and shape projects for the next stages. We spoke to recently appointed UK DRI Emerging Leader and Race Against Dementia Fellow at Cardiff, Dr Wioleta Zelek, about her research journey and experiences of developing and patenting research tools.

Growing up in Poland with six siblings, Dr Wioleta Zelek was the first in her family to go to university, inspired and encouraged by her school science teachers. Having completed undergraduate and Masters degrees in Chemistry, she decided to move overseas, taking up a role as a Lab Assistant at University Hospital Wales in Cardiff, before switching into the local biotech industry. Although she flourished in this environment and was rapidly promoted up the career ladder, Dr Zelek felt a career change would be beneficial and decided to explore academic opportunities, despite the associated drops in salary.

“I knew it was a risk, but sometimes you have to take a step back to take two jumps forward. I knew if I wanted to move to academia and pursue a research career, I had to do this. There's no way to progress without having a PhD, and I wanted to be a research leader. When I put my foot in a research lab, I knew this is me. This is where I am. This is my place.”

With experience in assay development from her time in biotech, Dr Zelek joined the lab of UK DRI Group Leader at Cardiff, Prof Paul Morgan, as a Research Technician. It was in this role investigating biomarkers for diseases of the Central Nervous System, that Dr Zelek’s passion for the brain and developing treatments for dementia was sparked, and 18 months later she began her PhD in Prof Morgan’s Lab. Dr Zelek’s career has gone from strength-to-strength ever since, with Fellowships from Wellcome’s Institutional Strategic Support Fund and Health and Care Research Wales, through to her current funding award from Alzheimer’s Research UK’s Race Against Dementia (RAD) and appointment to UK DRI Emerging Leader. Her research focus throughout has been on a branch of the immune system called ‘Complement’, as she explains.

“Complement is the very first inflammatory response of the body to any assault. It is a cascade of proteins that counter bacterial infections, either by directly killing bacteria or provoking white blood cells to eat them. When inappropriately triggered however, it can drive harmful inflammation - in two ways. A group of proteins known as the membrane attack complex (MAC) can directly assemble on a brain cell and cause it to leak or lyse. The leaking cells initiate more inflammation. Indirectly, the triggering of Complement leads to the release of pro-inflammatory products, for example C3a and C5a. These activate immune cells in the brain called microglia, causing secondary indirect damage to neurons.

In this latest RAD Fellowship, I'm looking at inhibiting MAC, which is at the latter stage of the complement cascade formation. And the question is, by inhibiting MAC, can we stop damaging inflammation in the brain and pathology of Alzheimer’s disease?”

Dr Zelek’s projects targeting Complement often have a translational component. During her PhD, she aimed to target and drug novel pathways in this system, focusing on the protein C7, which up until now has received less attention. A major part of the project was to develop screening assays to identify antibodies that didn’t just bind C7 molecules, but crucially, inhibited them. The work has resulted in a toolbox of novel Complement inhibitors, including patent protected drug candidates and other reagents enabling the study of this inflammatory mechanism in animal disease models.

“When obtaining the patent, I had great help from my supervisor and technology transfer innovation team, who led me through this process. We filed a patent application three years ago and hopefully it will be granted this year. It was a good experience, and I think having my industrial experience helped a lot because I used to work closely with customers, lead on the projects and deliver them to high requirements, writing long reports on the performance and failures etc. The innovation team was a connection between us and the lawyers, so it took quite a bit of mental effort to keep focused, read the patent and check everything carefully. There were many sequences and we had to make sure everything was copied in the right way and the data presented as we would like. The claims we made actually evolved as the project was progressing because we found out more about those antibodies, like how they bind, what they block and what their other applications could be, so we also included more diseases. Going forward, it will definitely be easier for me to write the next patent and work with a tech transfer office.”

Last year a collaboration between Dr Zelek, Prof Morgan and Prof John Davis (Alzheimer’s Research UK, Oxford Drug Discovery Institute) received one of the first UK DRI Translation Awards – an initiative to fund pre-clinical analysis, drug target validation or other work directly related to finding treatments. Dr Zelek discusses the progress made so far.

“It's a very exciting project, aiming to put the brakes on a very early component of the cascade - C3 convertase. We think that inhibiting C3 completely might be dangerous, as we do need these pathways to stop bacterial invasion. So, with this project we’re testing whether just inhibiting the convertase, rather than stopping it completely, is the best way to responsibly control the cascade.”

The team at Cardiff will be developing a robust, high-throughput screening assay to test for inhibitory drugs, as part of an automated library screening system based at the Alzheimer’s Research UK’s Oxford Drug Discovery Institute. With so much exposure to the processes and legalities behind biomedical translation, Dr Zelek offers her advice to other early career researchers.

“Staying alert is key. Ask questions to your supervisor and your TTO. I was keen to patent my screening assay, but I was told that it's probably not the best idea as it's very difficult, takes time and might not actually be possible at all. So that's why we went for the agents that came through the screening rather than the assay itself. It was interesting and useful to find that it's quite difficult to patent a process, rather than a product. Even after this experience it can still be quite confusing, for example deciding whether products such as new antibodies should sit within existing or new patents.

Collaboration is great. We’ve been working with another lab to develop fused proteins to help uptake of our agents in the brain, and that's just amazing. So that’s a way of making your research go further and opening up opportunities. Being part of Institute networks like the UK DRI really help with this.”

Dr Zelek's new review "Targeting complement in neurodegeneration: challenges, risks, and strategies" is now available in Trends in Pharmacological Sciences.

We'd like to thank Dr Zelek for taking the time to speak to us - you can find out more about this research on her UK DRI or RAD profile. If you have questions about translation and your research project, please contact the UK DRI Innovation and Business team, led by Dr Kay Penicud. You can also find further information on translation and innovation in this UK DRI Q&A with Dr Penicud.


Article published: 09 March 2022