Project Description for Find-A-PhD Advert (max 400 words). This will be the text that is advertised to prospective students:
Ageing-associated disease is a major public health challenge and there is an urgent, unmet need for strategies that promote healthy ageing. During ageing, tissues structurally deteriorate, leading to impaired physiological function and an increased vulnerability to disease and death. A hallmark of ageing is the progressive degeneration and atrophy of subcutaneous white adipose tissue (SAT). In the elderly, SAT loss is associated with increased disease and mortality.
Moreover, SAT maintains systemic metabolic health across all life stages – in weight-matched individuals, for every standard deviation decrease in SAT, the risk for metabolic disease increases by 48%. Therefore, maintaining SAT function is key for efforts to promote healthy ageing.
In ageing SAT, adipose stem cells become senescent, enter an irreversible cell-cycle arrest, and progressively lose the capacity to proliferate and differentiate. This ‘stem cell exhaustion’ leads to a diminished stem cell pool and a decreased ability to sustain SAT function and mass. Strikingly, ablation of senescent adipose stem cells rescues age-associated SAT degeneration and restores metabolic function in old age. Our hypothesis is that by identifying and understanding the molecular mechanisms that promote adipose stem cell function we can establish therapeutic targets for stimulating adipose homeostasis and regeneration in ageing.
This project has computational and wet-lab components, to be carried out in the groups of Dr Linus Schumacher and Dr James Minchin, respectively. The balance between these two approaches is flexible. The experimental work will utilise a novel zebrafish model system to investigate age-related SAT degeneration and regeneration. Specifically, we will utilise new transgenic zebrafish lines that enable the real-time visualisation of SAT stem/progenitor cells in vivo. Use of these new transgenic lines enables dynamic cell-cell interactions during SAT degeneration to be visualised for the first time. In addition to in vivo imaging, the project will also utilise genetic data from human longevity studies and transcriptomic/proteomic data to identify new candidate SAT degeneration genes. The function of a subset of these candidate genes will then be tested using CRISPR mutagenesis in zebrafish. Altogether, this project utilises a in vivo imaging in a new zebrafish model to identify and understand the cell and molecular mechanisms influencing age-related SAT degeneration.
Please refer to UKRI and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.
EASTBIO Application and Reference Forms can be downloaded via http://www.eastscotbiodtp.ac.uk/how-apply-0
Please send your completed EASTBIO Application Form along with a copy of your academic transcripts to [Email Address Removed]
You should also ensure that two references have been send to [Email Address Removed] by the deadline using the EASTBIO Reference Form.
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