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3D OrbiSIMS for the investigation of the molecular fingerprints of cellular senescence


   School of Pharmacy


About the Project

As we age our tissues accumulate senescent cells, which play important roles in health and disease across the lifespan. During aging and age-related conditions (i.e. Alzheimer’s disease, osteoarthritis, etc.), senescent cells accumulate and release molecules that harm neighbouring cells. Under other conditions such as cancer or wound healing, senescent cells can prevent tumor growth or promote new tissue growth.

Telomere shortening, oxidative and genotoxic stress, radiation and oncogenes are typical stimuli capable of inducing cellular senescence. Human cells become senescent when cell division stops. Whilst remaining viable, senescent cells undergo distinct phenotypic alterations, including flattened and enlarged morphology, altered composition of the plasma membrane and nuclear enlargement. Senescence is associated with multiple molecular changes reflecting profound alterations in cellular metabolic activity and gene programs along with chromatin remodelling and engagement of persistent DNA damage response.

Cellular senescence occurs progressively and is heterogeneous and dynamic in nature, with molecular changes that vary in a time, tissue and cell type dependent manner. Although a few common hallmarks of cellular senescence exist, the senescent phenotype is highly diverse, with underlying mechanisms not necessarily conserved among the various senescence programs. Existing senescence markers are not specific, and some of them can only be detected in vitro. Thus, multiple senescence-associated markers must be used, and the identification and characterisation of senescent cells remains challenging, especially in vivo.

3D OrbiSIMS allows label-free, untargeted high-throughput chemical imaging and analysis. Compared to other established mass spectrometry methods, 3D-OrbiSIMS allows analysis of biological samples in situ bypassing sample preparation, which can alter samples; has relatively high resolution (2mm), enabling visualization of spatial distribution of analytes within cells; and simultaneously identifies a range of chemistries.

This project aims to develop a method to characterize the biochemical fingerprints of cells that allows to distinguish senescent and non-senescent cells. Efficient identification and characterization of senescent cells will help understand senescent programmes and identify specific markers and therapeutic targets.

The successful candidate will receive training in mammalian cell culture, 3D OrbiSIMS analysis and data processing and analysis in addition to immunoassays and biochemical assays for assessing senescence and validation and measurement of candidate biochemicals.

The School of Pharmacy is ranked 5th in the world in the 2021 QS World Rankings for pharmacy and pharmacology.​ We are ranked 4th in the UK for our research quality in the REF2021 results. 96% of our research is world-leading or internationally excellent. Our research environment is 100% world leading. 


Funding Notes

The studentship funds tuition fees at Home level. If an International applicant were successful in the recruitment process they would need to make up the difference between Home and International tuition fees.

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