SP1 Dietary mediated changes of stress responses in ageing stem cells

Project Leader: K. Lenhard Rudolph

Background and previous work
Declines in the functionality of stem cells contribute to tissue ageing. In previous work we identified checkpoints that limit stem cell function in response to ageing associated accumulation of DNA damage and telomere shortening. Ongoing work from our group shows that dietary restriction (DR) enhances hematopoietic stem cell (HSC) quiescence but induces the capacity of HSCs to differentiate into lymphoid progenitor cells.

Specific aims and working programme
The main aim of this project is to delineate the role of (DR) in changing stress responses and differentiation capacity of stem cells in response to DNA damage and ageing. To address this question a lentiviral screen (pooled shRNAs or CRISPR/Cas9 libraries) will be conducted to identify genes that alter the influence of DR on HSC quiescence and differentiation. The function of candidate genes will be analysed to focusing on their influence on cell cycle, selfrenewal and differentiation control. Possible interconnection of candidate genes to Sirt1- dependent roles in DNA damage response will be investigated. The required methods for in vivo functional screens on HSCs are established in our laboratory.