Title of project

Towards a better understanding of the adverse effects of type 2 diabetes on hypertrophic cardiomyopathy

Abstract

The combination of type 2 diabetes mellitus (T2D) and hypertrophic cardiomyopathy (HCM) is very severe, leading to heart failure and excessively high mortality rates. The aim of the present study is to unravel the molecular mechanisms of such damaging combination (T2DHCM) by focusing on the most abundant cardiac protein, myosin. Specifically, I will determine how myosin ATP demand is changed in T2D-HCM; I then will define the causes of such altered myosin ATP consumption in T2D-HCM; finally, I will identify the metabolic consequences of the modified myosin ATP demand in T2D-HCM. Experiments will be run on myectomy specimens from HCM patients with and without T2D as well as on donors. I will apply a broad range of techniques involving cellular fluorescent probes, X-ray diffraction, molecular dynamics simulations, targeted and untargeted proteomics. Most of these methodological approaches will be performed at UCPH (in Dr Julien Ochala’s group) but also at QMUL, London (in Dr Arianna Fornili’s group). The findings of the present study will not only give valuable insights into the pathogenesis of T2D-HCM, they will also allow the identification of potential novel targets for intervention for this under-appreciated and orphan disease.