How do different gene mutations cross talk with Tor and Notch signalling outputs of the Tuberous Sclerosis complex?

Mutations in human Tuberous sclerosis complex, TSC-1 and TSC-2 genes cause a serious and incurable genetically inherited disorder, which is associated with tumour-like growths with cell-lineage defects in multiple organs. TSC regulates mTor signalling and tor inhibitors are partially effective in supressing some disease manifestations. We have identified a novel output of TSC acting through Notch, which is independent of Tor. In this project the student will use Drosophila model genetic organism and pluripotent stem cell technology along with CRISPR/CAS9 gene editing to elucidate the mechanism by which this cross talk takes place and determine how TSC-1 or 2 disease mutants located in different domains affect different pathways. The results will contribute ability to stratify different patient mutants for potential targeted therapies and maps onto the theme of precision medicine. Working with the Tuberous Sclerosis Association during a three month CASE placement the student will participate in the construction of patient database of disease life histories, learn different aspects of the charities' functions, including organising scientific and lay meetings, fundraising and writing lay articles the association's magazine and website. This project offers a unique opportunity to combine interdisciplinary research while interacting with and participating in the work of a disease focussed charity.