The dramatic increase in the size of the elderly population in the UK and other developed countries results in the increased risk of age-related pathologies, including cancer and chronic wounds, and, therefore, is associated with clinical and socio-economic burdens. The investigation of the mechanisms of ageing and development of the corresponding models to test different treatment modalities to retard or prevent ageing become a priority topic for bio-medical research.
Naked Mole Rats (NMRs, Heterocephalus glaber) are unique long-lived rodents with a life-span approximately ten-fold longer than mice or rats. NMRs possess marked resistance to age-related conditions (cancer, cardiovascular disease, or neurodegeneration) and maintain sustained health span for up to 32 years.
The goal of this project will be:
a) To develop 3D organotypic culture model of the NMR skin as new tool for manipulating the gene expression signatures and epigenome in distinct cell populations (epithelium, mesenchyme) to define the mechanisms underlying the NMR resistance to ageing and cancer.
b) Assess the suitability of the 3D organotypic NMR skin cultures for modeling a number of ageing-associated skin pathological conditions including altered skin repair after injury and carcinogenesis.
Models and techniques will be used:
- Gene expression analysis by qPCR, in situ hybridization and immunohistochemistry - Cell culture: the effects of selected genes on cell proliferation, differentiation and apoptosis will be assessed by the FACS, TUNEL, and qPCR and Western blot analysis. - Cell transfection with lentiviruses and use them for establishment of 3D cultures of NMR skin.