Analysis of MAP4K3 function and regulation in cancer

ANALYSIS OF MAP4K3 FUNCTION AND REGULATION IN CANCER
The mechanistic target of rapamycin (mTOR) pathway is overactivated in around 3/4 of human tumours. mTORC1, the protein kinase complex that is sensitive to ramamycin, is stimulated by several oncogenes frequently activated in cancer, including Ras and PI3K, as well as by loss of function of tumour suppressors such as PTEN and LKB1. mTORC1 is normally regulated by extracellular cues, including signaling from
growth factors/RTKs (Receptor Tyrosine Kinase) and nutrients, and plays multiple critical roles in regulation of cancer cell growth and metabolism. Amino acids provide one of the key nutrient inputs into mTORC1 activation, and we previously identified MAP4K3 as a mediator of amino acid-dependent mTORC1 activation. We now wish to identify how MAP4K3 stimulates mTORC1 activity, focusing initially on a
potential MAP4K3 substrate identified by biochemical and bioinformatics approaches. In addition, using an FDAapproved compound library and kinase-selective inhibitor sets, we will screen for novel inhibitors of MAP4K3 that might prove useful in identifying further cancer-relevant processes regulated by this enzyme. Finally, we will investigate how missense MAP4K3 mutations found in human tumours impact upon enzyme activity and mTORC1 activation and establish whether MAP4K3 expression is altered in colorectal and pancreatic cancers.

QUALIFICATIONS:
Applicants should hold a first-class or upper second degree in a molecular biology, biochemistry or cell biology-based degree.
Please note the English Language Requirement for EU/Overseas Students is an IELTS score of 6.5 with no band score lower than 5.5.

APPLICATION:
To apply please send a CV to Dr. Richard F. Lamb (email: [Email Address Removed])