BMC/GPMLS Lecture - Tom McWilliams

Tom McWilliams will give a presentation in the BMC/GPMLS lecture series titled Physiological autophagy in space and time. The lecture will be in English.

Short abstract: Mitophagy sustains lifelong tissue integrity by preventing the accumulation of dysfunctional mitochondria and alleviating metabolic stress. Mitophagy declines with age in short-lived model organisms, yet its physiological regulation in the aging mammalian brain and its relationship to other autophagy pathways remain poorly defined. I will present new insights into the spatiotemporal dynamics of mitophagy in the aging mammalian brain. Using high-resolution spatiocellular mapping of genetically encoded optical reporter mice, we reveal striking cell type-specific differences in basal mitophagy in vivo, challenging the notion of a uniform homeostatic process in the mammalian brain. We further reveal previously underexplored cellular subsets where mitophagy is either sustained or decreased in aging, providing mechanistic insights into selective neural resilience and vulnerability in vivo. Moreover, our longitudinal data reveal that midlife represents a critical inflection point hallmarked by the onset of lysosomal dysfunction, potentially priming selected neuronal populations for age-related decline. Integrating these findings with emerging human data and unconventional model systems, I will discuss how the spatiotemporal modulation of organelle homeostasis in neural networks is central to our understanding age-related neurological decline. Our work recasts physiological mitophagy as a dynamic cell and circuit-specific process in vivo, with implications for therapeutic strategies aimed at preserving mitochondrial integrity in the aging brain.

Tom McWilliams is Associate Professor of Mitochondrial Medicine at the University of Helsinki, Finland. He studied biochemistry in Ireland before moving to the UK to complete the Wellcome Trust Four-Year PhD Programme in neuroscience with Alun M. Davies FMedSci FRS and Stephen B. Dunnett FMedSci. Subsequently, he was recruited to the MRC Protein Phosphorylation and Ubiquitylation Unit, where he made groundbreaking advances in the study of physiological mitophagy and Parkinson’s disease with Ian Ganley and Miratul Muqit FMedSci. These observations of basal mitophagy reshaped the field and provoked a critical reassessment of this process in mammals. Building on this, his lab has made major contributions to our understanding of the clinical relevance of autophagy in humans, and the temporal modulation of mitophagy pathways. In 2021, he was elected a Scholar of the FENS-Kavli Network of Excellence - recognising Europe's leading young neuroscientists. In 2023, he was profiled as a "Cell Scientist to Watch". Tom and his team have been generously funded by numerous sources, including the Novo Nordisk Foundation, the Jane and Aatos Erkko Foundation, and the Research Council of Finland. A major focus of the lab is on understanding tissue-specific autophagy mechanisms, metabolic signalling, and neurodegeneration, with particular interest in identifying early inflection points and mechanisms that drive disease progression.
Interview with Tom: https://journals.biologists.com/jcs/article/136/20/jcs261604/334181/Cell-scientist-to-watch-Thomas-McWilliams