Postgraduate Opportunity at Institute of Marine Biotechnology (IMB),
Universiti Malaysia Terengganu (UMT)
IMB is seeking a Ph.D. candidate with a degree in Biotechnology majoring in Molecular Biology (or in related discipline) with a minimum cGPA of 3.00 and M.Sc. in Biotechnology/Molecular Biology (or in related discipline) to be part of a growing number of highly-motivated postgraduate students in the institute.
The candidate must posssess a critical thinking skill and intellectual rigour as well as competent laboratory techniques in animal cell culture (including transfection and luciferase assay), cell biology and molecular biology (cloning, RNA extraction, real time PCR, site-directed mutagenesis, western blot analysis, electromobility shift assay (EMSA) and immunohistochemistry).
Elucidation of the mechanisms of action and signal transduction pathways of marine bioactive compounds in reducing the progression of atherosclerosis by targeting PCSK9
Brief description of the project
Atherosclerosis is ranked first amongst the diseases that cause mortality globally. It is caused by an elevated plasma levels of low density lipoprotein-cholesterol (LDL-C). In order to maintain the homeostatic levels of LDL-C, excess LDL-C is removed from circulation by LDL receptor (LDL-R) present on the cell membrane of hepatocytes. The complex of LDL-R and LDL-C is then internalised into the cells via endocytosis. Once inside the cells, LDL-R is dissociated with LDL-C and LDL-R is recycled back to the cell surface. Therefore, LDL-R plays an important role in regulating the LDL-C to its normal levels. However, an enzyme known as PCSK9 binds to LDL-R, and, subsequently leads to the degradation and reduction of the number of LDL-R on the surface of liver cells. In fact, one of the adverse side effects produced by statins, a well known drug to reduce the levels of plasma cholesterols and the progression of atherosclerosis, is to increase the levels of PCSK9 which by contrast will reverse the function of statin. Therefore, PCSK9 forms a good target to identify marine natural compounds as a potential drug-like molecules in reducing the plasma cholesterol levels and subsequently the progression of atherosclerosis.
However to date, no report has demonstrated a comprehensive dissection and elucidation of the mechanisms and pathways that marine compounds used, to reduce PCSK9 gene transcription and increase LDL-R on the surface of liver cells, and, subsequently the uptake of LDL-C. Therefore, it is important for a study to be carried out to unlock the fundamental knowledge of the interaction between transcription factors and cis-acting elements of PCSK9 promoter, and, components of signalling routes that are responsible in mediating the regulatory effects of marine compounds on PCSK9 gene transcription as well as the translocation of LDL-R to the cell membrane and the uptake of LDL-C by liver cells.
Interested, please email or contact:
Prof. Tengku Sifzizul Tengku Muhammad
firstname.lastname@example.org or 09-6683103/4