Single-cell multi-omics sequencing to study the cell biology of ageing

Ageing is the process of functional decline of our organs, and is among the main risk factors for most human diseases. The causes of ageing are still largely unknown. However, understanding the cell biology of this process will have major medical, economical and societal impact, and will enable the development of anti-ageing products, the market of which is estimated to reach $331.41 billion by 2021 mainly through novel technological breakthroughs. A human body comprises 10 to 100 billion cells (= 10 to 100 x 1000.000.000.000 cells). As ageing is characterised by functional decline and most of our organ functions are executed by the concerted action of many different cells in a spatially organised context, it is paramount to not only research those individual cells, but also to study them in their native spatial context. To understand the ageing process, we need to investigate how (subpopulations of) cells become functionally perturbed over time and through environmental exposures. This PhD will establish single-cell multi-omics and spatial analytical frameworks to comprehensively study the heterogeneous cell biology of ageing, using photo-exposed and - protected human skin as a model. Specifically, we will investigate how somatic DNA mutation and epimutations may lead to functional perturbations of cells belonging to different types within a tissue context.