Research Fellow in Extracellular Matrix and High Throughput Screening

at  University of Surrey

RESEARCH FELLOW IN EXTRACELLULAR MATRIX AND HIGH THROUGHPUT SCREENING

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This is a new, exciting Post-Doctoral opportunity funded by the Medical Research Council (Grant Ref: MR/Z506266/1) in collaboration with AstraZeneca to identify small molecule inhibitors of the metalloprotease ADAMTS8. Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disease characterised by high blood pressure in the vessels that bring blood from the heart to the lungs, leading to heart failure.
As no cure exists for PAH, it is critical to develop agents able to halt or slow down its progression. A hallmark of PAH is the accumulation of proteins within the cardiac tissue, also called fibrosis, that severely impairs the ability of the organ to contract and work. Recently, the metalloprotease ADAMTS8 has been identified as a detrimental factor in the progression of PAH: 1) ADAMTS8 levels are significantly increased in the lungs of PAH patients; 2) mice genetically modified to lack ADAMTS8 showed less cardiac and vascular fibrosis which ensured protection from severe PAH.
Therefore, targeting ADAMTS8 activity may be a novel approach to treat PAH. Unfortunately, no molecules able to block ADAMTS8 activity are currently available. Here, we will perform a high throughput screening of the AstraZeneca proprietary library (>500,000 compounds) to isolate molecules able to block ADAMTS8 activity using a Förster resonance energy transfer (FRET) peptide as a substrate.
The post will be based in the Discipline of Clinical Sciences in the School of Biosciences and Faculty of Health and Medical Sciences at the University of Surrey. The project will be run in collaboration with AstraZeneca. The successful candidate will spend a short period at the AstraZeneca facilities in Cambridge, UK.
The main focus of the project will be to screen the AstraZeneca proprietary library to identify inhibitors of the metalloproteinase ADAMTS8.