Ageing and the heart: What is the impact of altering myostatin signalling? (360G-Wellcome-216925_Z_19_Z)

Ageing is a major cause of heart failure and contributes to increased motarlity and morbidity across the world. Age-induced cardiac dysfunction occurs as a result of structural and molecular changes to both the contractile and non contractile cells. In this project, we will use a progeroid Ercc1-/Δ mouse as means of testing the effects of targeting the myostatin signalling pathway in the myocardium during the ageing process. This studentship will allow me to use a number of different techniques to determine how cardiac morphology and gene expression is altered in this mouse model of accelerated ageing and determine the effects of inhibiting myostatin signalling. The project will use a combination of immunostaining, fluorescence microscopy and Western blotting. Left ventricular frozen tissue sections will be immunostained for caspase 3 and gamma-H2AX to measure apoptosis and DNA damage respectively. Western blotting will be used to measure the phosphorylation of ERK1/2 and p38 MAPK in tissue homogenates as a measure of myocyte hypertrophy signalling. This will give me experience in two different laboratories and allow me to learn how research questions are tested experimentally. Additionally this will help improve our understanding of heart failure during the ageing process.