Marcelina Wojewska is a PhD student working across two laboratories at the Department of Brain Sciences, Imperial College London. She investigates why the same protein behaves so differently in two devastating brain diseases – Parkinson’s disease and Multiple System Atrophy.
She talks about the science behind her research, the challenges of working with human brain tissue, and what keeps her curious.
Could you tell us about your journey into neuroscience research? What initially drew you to studying neurodegenerative diseases?
During my undergraduate degree in biochemistry, I became particularly interested in how subtle biochemical changes can ultimately lead to large-scale effects, such as the devastating disease caused by single amino acid mutations. I did my undergraduate project in the lab of Professor Stephen Brickley, and I began learning about neuronal computations that occur in the brain during vision. My journey into neuroscience really began with a fascination for how the brain works and what happens when such a complex system goes wrong. What drew me specifically to neurodegeneration was the combination of scientific complexity and human impact. Disorders like Parkinson’s disease and Multiple System Atrophy are devastating for patients and families, and despite the advances we have made, we still lack meaningful disease-modifying treatments.
Your PhD research focuses on the strain hypothesis of alpha-synuclein in Multiple System Atrophy and Parkinson’s disease. Could you explain what the strain hypothesis is and why understanding it is so crucial for these conditions?
The strain hypothesis proposes that misfolded alpha-synuclein, the protein that forms the aggregates found in Parkinson’s disease and Multiple System Atrophy, can adopt distinct structural configurations, or “strains.” These strains may differ in how they spread, which cell types they affect, and the amount of damage they can do. This is particularly important because although in both conditions we see aggregates of the same protein, these diseases are very different clinically and pathologically. In Parkinson’s disease, alpha-synuclein primarily accumulates in neurons, whereas in Multiple System Atrophy it predominantly accumulates in another type of cell, oligodendrocytes. The strain hypothesis offers a possible explanation for this divergence. Understanding whether different conformations drive different diseases could transform diagnostics and therapeutic strategies. If we can define disease-specific strains, we may be able to design more targeted interventions rather than treating these diseases as a single entity.
What makes this area of research particularly exciting or challenging?
What makes it exciting is that we’re operating at the frontier of structural biology, neuropathology, and disease modelling. New imaging and biochemical techniques are allowing us to interrogate protein aggregation in ways that weren’t possible even a decade ago. The challenge is that we’re studying incredibly complex biological systems using post-mortem human tissue, which carries variability and limitations. Interpreting heterogeneity, distinguishing meaningful biological differences from noise, requires both technical rigour and conceptual flexibility. But that complexity is also what makes the discoveries so rewarding.
Are there any technical challenges or breakthroughs you’ve encountered in your work?
Working with human post-mortem brain tissue presents unique technical challenges, such as preservation quality, regional variability, and the need for highly sensitive detection methods. Optimising immunohistochemical and biochemical protocols to reliably detect different conformations of alpha-synuclein has been a significant part of my work. One particularly rewarding breakthrough has been refining approaches that allow us to visualise the functional ability of individual aggregates within tissue to “seed” by recruiting more protein and growing.
Working in both Professor Steve Gentleman’s and Professor Javier Alegre-Abarrategui’s laboratories must provide diverse perspectives. How do you navigate and benefit from these research environments?
Working across both Professor Steve Gentleman’s and Professor Javier Alegre-Abarrategui’s laboratories has been incredibly enriching. The Gentleman lab brings deep expertise in neuropathology and human tissue analysis, while the Alegre-Abarrategui lab offers strong mechanistic perspectives of protein aggregation, which aid the development of novel tools to detect early aggregation events. Navigating both environments has taught me adaptability, understanding how to communicate and integrate different methodological approaches. It’s strengthened my ability to think about disease from multiple angles, from tissue-level pathology to molecular mechanisms. This experience has shaped the way I design experiments and interpret findings.
What advice would you give to other young women who are interested in pursuing careers in medical research?
I would say, don’t wait until you feel “ready”. Research is something you grow into. Confidence often follows experience, not the other way around. Seek mentors and collaborators who value your ideas and support your development. Science thrives on diversity of thought, and your perspective is an asset. Also, don’t ever stop asking questions; curiosity is a powerful driver in research.
What do you do outside of your professional life to decompress and maintain balance?
I try to maintain balance by stepping completely outside the lab environment when I can, whether that’s spending time outdoors or catching up with friends and family. Having activities that are unrelated to research helps reset my perspective and maintain creativity. I’ve found that some of my best ideas emerge when I’m not actively thinking about experiments.
Is there any forthcoming research project you’d like to mention?
I’m currently working on further characterising alpha-synuclein aggregate heterogeneity in Multiple System Atrophy using complementary histological and biochemical approaches. The goal is to better understand how pathology progresses throughout the brain, and how the structure and seeding ability of alpha synuclein changes as the disease progresses. It’s an evolving area, and I’m excited about the possibility that refining our understanding of strain diversity could eventually inform more precise diagnostic tools or therapeutic strategies.