Project 02: Role of PP2A-B56α in β-adrenergic regulation of cardiac function

PI London: M. Avkiran; PI Göttingen: N. Voigt; PhD: A. Güran - finished PhD

The primary focus is on the signal transduction pathways, particularly those that function through altered protein phosphorylation, which regulate cardiac function in health and disease. The supervisors' research programmes aim to gain new mechanistic knowledge and to identify potential new targets for therapeutic intervention, particularly in the context of heart failure. We focus on identifying and characterizing novel protein kinase and protein phosphatase pathways and novel substrates for the pertinent phospho-regulatory enzymes. Towards that aim, we utilize multiple techniques and models, including isolated cardiac myocytes, dynamic measurement of intracellular ion concentrations (using fluorescent indicators) and contraction (sarcomere shortening) in live cardiac myocytes, protein phosphorylation analysis (western blotting with phospho-specific antibodies, phosphate-affinity SDS/PAGE, mass spectrometry), in vivo manipulation of selected signalling and sarcomeric proteins by gene targeting, and analysis of cardiac structure (histology) and in vivo contractile function (high resolution echocardiography). The present PhD project will focus on studying cardiac excitation-contraction coupling in a novel model with genetic manipulation of protein phosphatase regulatory subunit B56alpha, encoded by the PPP2R5A gene, using a combination of the above techniques. The project will involve one or more periods working in Gottingen, to take advantage of the availability of cardiac electrophysiology and proteomics facilities and expertise at the host institution.

Contact