The role of hypoxia inducible factor 1-a in ischemia/reperfusion injury

The molecular events mediated in the cardiovascular effects of ischemia and ischemia/reperfusion injury are incompletely defined and further understanding would facilitate therapeutic modulation of these effects. The experiments described in this study will permit in vitro and in vivo studies leading to specific dissection of the role HIF1 signalling plays in the hypoxic response of cardiomyocytes and its role in ischemia/reperfusion injury. HIF-1 (HIF1a-ARNT), the hypoxia activated transcription factor, is a dimer made up of the basic helix-loop-helix molecules, HIF1a and ARNT. This factor is the principle effector of the transcriptional response to hypoxia during cardiovascular development and pathology. The effects of abrogating HIF1(a-ARNT signals are likely to be evident under conditions of cardiac stress, and we wish to evaluate these effects under conditions that are clinically relevant. The described study will provide training in the exacting techniques required for successful mouse modelling under direct supervision of Prof. Dr. Randall S. Johnson, who has extensive experience in the generation of transgenic and knock-out mice. Furthermore, I will be trained in cell targeting and in techniques for molecular biological analysis. A one year stay at Prof. Johnson`s laboratory allows me to learn a plethora of new techniques at one of the world`s foremost biology departments, as well as facilitating scientific exchange between that department and my institute.