Available Projects
Main location: King's College London
Phosphatase regulation of myocardial function. M Avkiran & A El-Armouche
Neurohormonal regulation of cardiac function is achieved principally through reversible phosphorylation of key proteins, including those that are involved in ion transport and muscle contraction downstream of receptor activation. Although much research effort to date has focused on identifying the kinase pathways that facilitate the phosphorylation of such proteins, there are also emerging roles for receptor-mediated regulation of protein phosphatases that serve the opposite function (i.e. protein dephosphorylation). This project will focus on exploring novel mechanisms that may regulate the localization and function of type 1 (PP1) and type 2A (PP2A) protein phosphatases, which together provide the majority of the serine/threonine phosphatase activity in myocardium.
Redox modification of ryanodine receptor function. P Eaton & S Lehnart
Myocardial infarction occurs from reduced coronary blood supply which is target of modern reperfusion therapy. However, ischemia followed by reperfusion can induce acute and chronic malignant changes in the heart. The signalling mechanisms, which control reperfusion injury, however, are incompletely understood. In this project we explore signaling mechanisms at the level of protein kinases, reactive oxygen species, and intracellular Ca2+ through unique mouse model. In particular, the cardiac ryanodine receptor Ca2+ lease channel will be investigated as a key signaling node in reperfusion injury.
Main location: Heart Research Centre Göttingen
Tissue engineering and stem cell proteomics. W Zimmermann & M Mayr
The extracellular milieu of the heart is mainly composed of matrix proteins and growth factors. Both play a vital role in cardiogenesis and cardiac homeostasis as they appear to form constructive and instructive micro-milieus within the heart. Tissue engineered myocardium, such as engineered heart tissue (EHT), constitutes a simplified test-bed with well defined cellular and matrix constituents. In this project proteomic exploration of extracellular matrix and secretome of EHT followed by knock-down and over-expression of identified factors in a novel embryonic stem cell-based EHT model will be used to identify key regulators of cardiogenesis and cardiac homeostasis.
Impact of the oxygen sensors PHD for myelo-angiogenic functions. DM Katschinski & A Shah
The hypoxia-inducible factor (HIF) and the HIF regulating prolyl-4-hydroxylase domain (PHD) enzymes (PHD) are the major driving force for postischaemic angiogenesis. In addition, they also control monocyte/macrophage function in ischaemic tissues. In this project myeloid-specific PHD knock out mice will be analyzed regarding the impact of PHD expression in inflammatory cells in ischemia models. i.e. myocardial ischemia and hind limb ischemia. A special focus will lie on the sequential analysis of inflammatory cell infiltration by MRI-imaging methods.
