Role of Satb1 in the control of topological genome organization during skin development and ageing

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In the era of tissue engineering and the development of novel approaches for stem cell-driven organ regeneration, it is important for researchers and physicians to understand how multi-potent stem cells differentiate into specialised cell types, and why these processes are altered during ageing and age-associated disorders, such as cancer, impaired tissue regeneration, wound healing, hair loss.Skin serves as an important and convenient model to study the biology of ageing process, and skin structure and functions are altered during ageing. Skin also serves as a source of adult stem cells, and several distinct adult somatic cell populations isolated from the skin were successfully employed for reprogramming and generation of induced pluripotent cells. Research into genome and chromatin biology over the last two decades has revealed that in addition to genetic mechanisms, lineage-specific gene expression programs are also regulated epigenetically, i.e., via biochemical modification of the chromatin structure. Genome organizer Satb1 protein plays an important role in establishing specific associations between different genes in the nucleus, which are required for proper control of cellular functions and gene expression programs.Satb1 protein regulates expression of the genes that are highly expressed in skin epithelial cells via establishing of specific three-dimensional conformation of the skin-specific genomic loci in the nucleus. However, its role in the control of skin ageing remains unclear. In this project, we propose a systematic study to 1) understand how skin-specific gene loci are spatially organised in the nucleus, 2) define genes that form their close genomic neighbourhood and 3) understand how Satb1 protein regulates these processes during skin development and ageing. Successful performance of this project will help in better understanding the complexity of regulatory mechanisms that control skin development and ageing and in designing new approaches for modulating ageing process and targeting stem cells in the clinical age-associated conditions accompanied by their un-controlled activation/expansion or exhausting/loss