英国爱丁堡大学癌症研究博士后职位
信息来源:未知 | 作者:admin | 时间:2014-04-14 21:01
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The drive to understand how altered cellular metabolism and cancer are linked has caused a paradigm shift in the focus of cancer research. The discovery of a mutated metabolic enzyme, isocitrate dehydrogenase 1, that leads to accumulation of the oncometabolite 2-hydroxyglutarate, provided significant direct evidence that dysfunctional metabolism plays an important role in oncogenesis. Striking parallels exist with the Krebs cycle enzyme fumarate hydratase (FH), a tumour suppressor, whose mutation is associated with the development of leiomyomata, renal cysts, and tumours. Loss of FH enzymatic activity results in accumulation of intracellular fumarate, which has been proposed to act as a competitive inhibitor of 2-oxoglutarate-dependent oxygenases including the hypoxia-inducible factor (HIF) hydroxylases, thus activating oncogenic HIF pathways. Interestingly, our studies have questioned the role of HIF and have highlighted other candidate mechanisms, in particular the non-enzymatic modification of cysteine residues (succination) that could lead to disruption or loss of protein functions, dysfunctional cell metabolism and cell signalling.
This post aims to appoint a highly skilled and motivated postdoc who will investigate multiple aspects of renal cancer metabolism through molecular and metabolic analysis of range of in vitro and in vivo models.
This post is available on a fixed term basis for a period of 3 years.
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