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Developing mitochondrial-targeted therapies for stem-cell rejuvenation
Secondary Supervisor(s): Prof Fabian Spill
University of Registration: University of Birmingham
BBSRC Research Themes:
Project Outline
Reversing stem cell exhaustion holds considerable promise for extending functional, healthy lifespan in older adults. However, current interventions are constrained by an incomplete understanding of the mechanisms that drive age-related functional decline.
Although multiple stressors can accelerate cellular ageing, compelling evidence highlights the loss of mitochondrial homeostasis as a central factor. Mitochondrial quality control (MQC) mechanisms —including mitophagy, biogenesis, and fusion/fission dynamics— are essential for adapting cellular metabolism to physiological demands, and are critical for maintaining stem cell function throughout life. With age, however, MQC become dysregulated, leading to altered bioenergetics and stem cell dysfunction.
We have recently identified a metabolic, non-canonical mechanism of stem cell exhaustion that operates independently of classical aging processes. Importantly, this mechanism can be rewired through a novel class of MQC-targeting molecules (Mito-REVs), offering an innovative strategy to preserve stem cell function across different system throughout the lifespan.
In this PhD project, the student will harness the versatility of Mito-REVs to:
• Define the mechanism by which they reverse exhaustion across different stem cell sources
• Assess their efficacy in enhancing the regenerative potential of aged stem cells
• Establish mitochondrial topology as predictive marker of stem cell ageing and rejuvenation
The successful candidate will employ a broad range of advanced approaches, including mitophagy reporters, bioenergetic and metabolic assays, epigenetic clocks, transcriptomics, molecular biology, and computational modelling. This PhD programme offers an exceptional opportunity to join an experienced supervisory team with expertise in mitochondrial biology and applied mathematics, providing the candidate with a unique interdisciplinary skill set to advance ageing research and regenerative biology.
