Postdoc start-up grant: mTOR in diabetic cardiomyopathy

The protein complex mechanistic target of rapamycin (mTOR) is involved in the development of many different diseases. In the failing heart mTOR is known to be hyperactivated, but its role in the diabetic heart remains controversial mostly due to lack of adequate models. Complete knockout models or transgenic overexpression models remain rather artificial. In data generated in the U.S. and Berlin, we developed a novel genetic mouse model, in which a more physiological fine-tuning of the mTOR complex can be achieved to regulate mTOR in both directions – to inhibit or hyperactivate. But, this mechanism is only active when the cell is exposed to a pathological stimulus. The healthy heart remains intact. In this project we study the influence of mTOR signaling in the diabetic heart. We already found exciting insights showing that mTOR (hyper-)activation contributes to a worsening of diabetic cardiomyopathy while mTOR suppression in the diabetic heart minimized disease progression. Altered autophagy and a shift in cell metabolism might be responsible for this mechanism. This we would like to investigate further, test new drugs to exploit this cellular mechanism to ultimately contribute to find a novel therapy for all the patients suffering from diabetes.