About the Project
Atherosclerosis is a process which causes ‘fat-laden’ scars or lesions in the walls of arteries. Such atherosclerotic lesions can grow and rupture, leading to arterial blockages that stop oxygenated blood delivery to organs such as the heart. Targeting scavenger receptor function is one strategy towards promoting repair and regeneration of damaged arteries after heart attacks. The aim of this PhD project is to use synthetic protein scaffolds called Affimers to target scavenger receptor function in atherosclerosis.
The PhD student will be trained in primary and immortalised cell culture, molecular biology, biochemistry, microscopy, cellular assays and cardiovascular disease. A broad-based PhD training will be supervised by Dr Vas Ponnambalam and Dr Darren Tomlinson focusing on training towards developing a career in academic research, pharmaceutical/biotechnology industry, healthcare and science-oriented sectors.
References
Billah MM, Hays HCW, Hodges CS, Ponnambalam S, Vohra R, Millner PA (2012) Mixed self-assembled monolayer (mSAM) based impedimetric immunosensors for cardiac troponin I (cTnI) and soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1). Sensors & Actuators B: Chemical 173:361-366.
Cubbon RM, Yuldasheva NY, Viswambharan H, Mercer BN, Baliga V, Stephen SL, Askham J, Sukumar P, Skromna A, Mughal RS, Walker AM, Bruns A, Bailey MA, Galloway S, Imrie H, Gage MC, Rakobowchuk M, Li J, Porter KE, Ponnambalam S, Wheatcroft SB, Beech DJ, Kearney MT (2014) Restoring Akt1 activity in outgrowth endothelial cells from South Asian men rescues vascular reparative potential. Stem Cells 32:2714-2723.
De Siqueira J, Abdul Zani I, Russell DA, Wheatcroft SB, Ponnambalam S, Homer-Vanniasinkam S. (2015) Clinical and preclinical use of LOX-1-specific antibodies in diagnostics and therapeutics. J. Cardiovascular Translational Research 8:458-65.
Helma J, Cardoso MC, Muyldermans S, Leonhardt H. (2015) Nanobodies and recombinant binders in cell biology. J Cell Biol. 209:633-644.
Mughal NA, Russell DA, Ponnambalam S, Homer-Vanniasinkam S (2012) Gene therapy in the treatment of peripheral arterial disease. Br J Surgery 99:6-15.
Shaw D, Seese R, Ponnambalam S, Ajjan RA (2014) Lectin-like oxidized low-density lipoprotein receptor-1 and atherothrombotic dsease: a novel approach for the management of vascular pathology? Diabetes Vasc Dis Res 11:410-418.
Tiede C, Tang AA, Deacon SE, Mandal U, Nettleship JE, Owen RL, George SE, Harrison DJ, Owens RJ, Tomlinson DC, McPherson MJ. (2014) Adhiron: a stable and versatile peptide display scaffold for molecular recognition applications. Protein Eng Des Sel. 27:145-155.
Twigg M, Freestone K, Homer-Vanniasinkam S, Ponnambalam S (2012) The LOX-1 scavenger receptor and its implications in the treatment of vascular disease. Cardiology Research & Practice 2012:632408.
Zani IA, Stephen SL, Mughal N, Russell D, Homer-Vanniasinkam S, Wheatcroft SB, Ponnambalam S (2015) Scavenger receptor structure and function in health and disease. Cells 4:178-201.