DC 11: Shifted metabolism in TSC patients: a new avenue for interventions

Project part of Work Package 2

Objectives: Metabolic differences are promising non-genetic candidate modifiers of the disease course in mTORopathies. Disturbed energy metabolism has been reported in mouse and rat models of TSC, but it is unknown whether this observation translates to human patients. DC11 will be assess this in TSC cell models by fluxomics and quantitation of intra- and extracellular metabolites in response to changes in nutrient supply. Recruited scientist will test the impact of bioenergetics by modulating gene expression and by pharmacological targeting in vitro and in vivo. In patient cohorts, the PhD candidate will evaluate the correlation between nutrient levels in TSC individuals with disease burden related to brain and kidney function.

Expected Results: Doctoral candidate will elucidate the molecular mechanisms underlying altered metabolism and the causal links with TSC symptoms in the brain and kidney.

Prospects of career development: The alumni from the Thedieck lab have successfully transitioned to new positions in both academia and industry. We support multidisciplinary training and advocate for active teamwork in science, providing opportunities for individual development of interests and career paths.

Planned secondments: 2 months at CNIO for testing the impact of bioenergetics on RAG and TSC outcomes in vivo. 2 months at KU Leuven and 2 months at UMC Utrecht to conduct metabolic profiling of TSC cohorts. 3 months at Mimetas to test amino acid intervention on kidney on chip.