About the Project
Can restoring mitochondrial health help ageing stem cells regain their regenerative potential?
Stem cells maintain and repair tissues throughout life, but their ability to do so declines with age. Understanding and reversing this loss of function, known as stem cell exhaustion, could unlock new approaches to healthy ageing and regenerative medicine.
Mitochondria are central of this challenge. Beyond producing energy, they coordinate the metabolic programmes that support stem cell function. Mitochondrial quality control (MQC) mechanisms, including mitophagy, biogenesis, and mitochondrial fusion-fission dynamics, maintain mitochondrial health and enable cells to adapt to changing physiological demands. With age, these processes become disrupted, contributing to metabolic imbalance, stem cell dysfunction, and impaired tissue repair.
We have recently identified a metabolic, non-classical mechanism of stem cell exhaustion that operates independently of established aging hallmarks. To target this pathway, we developed a novel class of mitochondrial quality control-modulating compounds, termed Mito-REVs, which restore stem cell function by reprogramming mitochondrial homeostasis. This provides a unique opportunity to determine whether mitochondrial rejuvenation can enhance stem cell function and regenerative capacity across multiple systems.
In this PhD project, the student will harness the versatility of Mito-REVs to:
- Define how Mito-REVs reverse stem cell exhaustion and reshape regenerative signalling.
- Assess their ability to enhance regenerative potential across distinct stem cell populations, primarily neural and skeletal stem cells.
- Identify mitochondrial biomarkers of stem cell ageing and rejuvenation to guide the development of next-generation mitochondrial therapeutics.
The project will provide training in a wide range of cutting-edge techniques, including live-cell imaging of mitophagy, bioenergetic and metabolic profiling, mitochondrial topology analysis, transcriptomics, epigenetic ageing clocks, and advanced molecular and cellular biology approaches.
This PhD programme offers an exceptional opportunity to join an experienced supervisory team with expertise in mitochondrial biology, neuroscience, bone remodeling and ageing, providing the candidate with a unique interdisciplinary skill set to advance ageing research and regenerative medicine.
Funding notes:
This is a PhD studentship with the Midlands Integrated Biosciences Training Partnership, funded by BBSRC and in partnership with the University of Warwick, University of Birmingham, Aston University, Harper Adams University, Coventry University, and the University of Leicester.
For more details please visit: https://warwick.ac.uk/fac/cross_fac/mibtp/ or https://www.birmingham.ac.uk/about/college-of-life-and-environmental-sciences/midlands-integrative-biosciences-training-partnership
References:
- Anderson A, Alfahad N, Wimalachandra D, Bouzinab K, Rudzinska P, Wood H, Fazey I, Xu H, Lyons TJ, Barnes NM, Narendran P, Lord JM, Rauz S, Ganley IG, Curtis TM, Wallace GR, Hombrebueno JR. Relaxation of mitochondrial hyperfusion in the diabetic retina via N6-furfuryladenosine confers neuroprotection regardless of glycaemic status. Nat Commun. 2024 Feb 6;15(1):1124.
- Neag G, Lewis J, Turner JD, Manning JE, Dean I, Finlay M, Poologasundarampillai G, Woods J, Sahu MA, Khan KA, Begum J, McGettrick HM, Bellantuono I, Heath V, Jones SW, Buckley CD, Bicknell R, Naylor AJ. Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning. Commun Biol. 2024 Oct 11;7(1):1296.
Project supervisors
Dr. Jose M Romero Hombrebueno
Dr Jose M Romero Hombrebueno obtained a PhD in Visual Neuroscience from the University of Alicante, Spain, in 2011, where he researched neuronal plasticity mechanisms in retinitis pigmentosa and refractive disorders of the eye. He was awarded a Pre-Doctoral Fellowship (FPU), which allowed him to visit several key institutions, including the University of Oxford, University of Southern California, and University of Newcastle, to enhance his research. In 2012, Dr Romero Hombrebueno joined Queen's University Belfast, focusing on the mechanisms of retinal degeneration associated with diabetic retinopathy and age-related inflammatory conditions. He received the Fight for Sight Early Career Investigator Award in 2016, enabling him to establish an independently funded research programme aimed at developing mitochondrial-based therapies for diabetic retinopathy. In 2019, he became a Hale-Rudd Lecturer in Experimental Ophthalmology at the University of Birmingham's Department of Inflammation and Ageing, where he aims to understand the impact of mitochondrial dysfunction on eye diseases and to develop novel therapies to prevent sight loss. Dr Romero Hombrebueno was promoted to Associate Professor in 2024.
Dr. Amy Naylor
Dr Amy Naylor completed her BSc (Hons International) in Biology at the University of Leeds in 2004, followed by an MRes in Medical and Molecular Biosciences and a PhD in Rheumatology at the University of Newcastle in 2005 and 2008, respectively, as part of the Oliver Bird Rheumatism Scheme. She then moved to the University of Birmingham to work with Professor Chris Buckley, where she was awarded a Foundation Fellowship from Arthritis Research UK to investigate stromal cell-specific markers in inflammation and repair. Since completing the fellowship, Dr Naylor has continued her career at the University of Birmingham, where she was awarded a prestigious 5-year Career Development Fellowship from Versus Arthritis in 2018. She currently leads a research team focused on the effects of inflammation and ageing on bone formation and turnover. Dr Naylor's research group aims to identify therapeutic targets to reverse bone loss associated with inflammation and ageing, collaborating with chemical and tissue engineers to develop complex in vitro models that better mimic physiological conditions. She has received grant funding from various organisations, including Versus Arthritis, AstraZeneca, the EPSRC, Wellcome Trust, MRC, NC3Rs, and the Chernajovsky Foundation.
