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?”