“There has never been a better time to be a mitochondriac!”

Mitochondrial research is undergoing a renaissance in the field of biomedicine, says Assistant Professor Thomas McWilliams. No wonder, since mitochondrial dysfunction seems to be linked with a breathtaking array of diseases.

Thomas McWilliams, Assistant Professor (Tenure Track) and Academy of Finland research fellow, is intensely interested in mitochondrial signalling and organelle crosstalk.

“Mitochondria lie at the heart of cellular metabolism. These rod-like structures exist within our cells and form a highly dynamic, almost ‘social’ network. They interact intimately with other organelles and generate the chemical energy that sustains life,” describes McWilliams.

In addition to energy production, mitochondria fulfil many other vital functions, and serve as the genetic repository of our maternal lineage.

The central role of mitochondria in cellular metabolism means that their dysfunction usually spells serious trouble. Indeed, mitochondrial dysfunction has been linked with a breathtaking array of human diseases. These include rare inherited disorders in addition to more common idiopathic diseases such as neurodegeneration, diabetes and cancer.

Clever cells: quality control and recycling

Our cells have developed elaborate ways to sense mitochondrial damage and ensure the smooth running of these vital power plants. Such mitochondrial quality control processes and their regulation in tissues are of particular interest to McWilliams.

In essence, one system revolves around autophagy – literally meaning from the Greek word: “to eat oneself”. This is a sophisticated recycling mechanism that our cells can exploit to destroy toxic or unnecessary components. “At home, we dispose of our waste by carefully separating it into different categories. Likewise, our cells can selectively identify harmful components and eliminate them,” explains McWilliams.

McWilliams’ lab is driven to understand how cells exploit this recycling pathway for damaged mitochondria. Dubbed ‘mitophagy’– this is a specialised quality control process that detects, neutralises and destroys damaged mitochondria.

For a decade already, mitophagy has been the focus of intensive research efforts from many labs around the world.

“Classically, mitophagy has been studied in cell culture by using chemical triggers to stimulate the process. This approach has enabled a highly detailed molecular dissection of how cells eliminate damaged mitochondria in response to stress. I think this work has been really vital, as revealed valuable molecular links between Parkinson’s disease and mitochondrial damage” says McWilliams.

"My own research has exploited cutting edge tools to visualise when, where and how mitophagy is happening within tissues. We discovered that rather than being merely a stress response, mitophagy appears to be a constant process within our tissues. There are striking differences in mitophagy between organ systems, cell subtypes and even during foetal development. It’s a very complex process in vivo, and much work remains to reveal the range of molecular signals that modulate mitophagy in different scenarios.”

 “These findings have unearthed an entirely new landscape to explore. I recently returned from the leading international conference in our field, and it was exciting to see that what we are doing is at the forefront of this research.”

Waste management issues

If cells are unable to effectively dispose of damaged mitochondria, this will likely result in dysfunction that causes disease. However, McWilliams cautions against jumping to conclusions:

“Much more research is needed to understand these processes. We must be cautious about oversimplifying and linking cellular pathways to diseases whose underlying mechanisms may be highly complex. Fortunately, we now have the right tools to investigate mitophagy and its regulation in a very rigorous and systematic fashion.

He remains defiantly optimistic: ”There has never been a better time to be a mitochondriac!”

Novo Nordisk Foundation convinced by mitochondrial researcher’s vision

Tenure Track Assistant Professor and Academy of Finland Research Fellow Thomas McWilliams is one of four young Nordic researchers who were this year awarded the prestigious Novo Nordisk Foundation Excellence Project for Young Researchers. The DKK 5 million grant was awarded for five years.

According to McWilliams, its significance to a research group taking its first steps is substantial.

“I am excited that the Foundation agreed with me on the importance of mitochondrial research and the direction in which this quickly developing research field is advancing. With this funding, I am establishing a completely new research direction based on some really exciting findings.

”I feel extremely privileged to accept this award, and I fully intend to make every use of it.”

From Galway to Helsinki, via Cardiff and Dundee

McWilliams, who started working as a Tenure Track Assistant Professor at the University of Helsinki in January 2018, is an Irish neuroscientist with a diverse scientific background. His career started as a student of biochemistry at the National University of Ireland in Galway. He received his doctorate in Integrative Neuroscience at Cardiff University, UK under the supervision of Professor Alun M. Davies FRS, an established leader in neurobiology.

“Alun’s influence in my evolution as a researcher was profound. He taught me to be scientifically fearless and how to investigate challenging problems in a rigorous, interesting and independent fashion”, says McWilliams.

After receiving his doctoral degree and finishing projects in the Davies lab McWilliams worked for three years on signalling related to neurodegenerative disease, as a post-doctoral researcher at the MRC Protein Phosphorylation & Ubiquitylation Unit. This institute, embedded within the University of Dundee in Scotland is an internationally renowned mecca for signal transduction and biochemistry.

“During that period, I was fortunate to work with Ian Ganley and Miratul Muqit, two particularly brilliant researchers. I quickly became enraptured by mitochondrial signalling and autophagy in tissues. The intersection of these fields constitutes very competitive, fast-paced area of biomedical research.”

Towards the end of his post-doctoral research, McWilliams was looking for a suitable location to establish his own research laboratory and team. This was an opportune moment to learn about the Tenure Track system at the University of Helsinki.

“Due to its excellent reputation in these research areas, the University of Helsinki was an obvious choice.”

McWilliams’ research group is part of the Molecular Neurology Research Programme of the Faculty of Medicine. He relishes the opportunity to lead his own independent research group and values the close collaborative links that he has established with leading researchers in the field, who are also on faculty.

“Moreover, Finland is a really cool place - there is something special happening here right now! The Finnish strength of character and holistic attitude towards wellbeing is something that resonates very strongly with me. This is a productive and competitive place, with a healthy dose of perspective. Although I am only here since January, I am very happy!”

McWilliams Lab