Using Chemical Biology to Monitor Impact of Metabolic Perturbations on the Regulation of Chromatin State and Drug Action

Organisms respond to environmental changes by adjusting their physiological state, for example switching to oxygen-independent metabolism if oxygen provision is limited. Such coping mechanisms are encoded within the genetic information which provides the template for a cellular response.

This is the reason why geneexpression and metabolism are highly interconnected via crosstalk between nutrient availability and the accessability of genetic information, the chromatin state.

This interdependence has been shown to affect and contribute to many human disorders such as cancer and inflammatory diseases.

Not surprisingly, alterations in metabolite pools can also have a significant impact on the therapeutic efficacy of drugs.

With this project I’m aiming to develop methods and tools to monitor cellular responsiveness to drugs in the context of metabolic perturbations in cells to identify and define sensitivity patterns as well as factors that may provide novel therapeutic opportunities.