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The Role of LIM Domain Only Proteins in Neuroblastoma


Institute of Cancer and Genomic Sciences

Applications accepted all year round Self-Funded PhD Students Only

About the Project

Person Specification

An Upper Second Class Honours Degree (or equivalent) in a relevant study or Master’s degree is expected. Prior experience in cell and molecular biology is an advantage. If applicable, proof of proficiency in the English language is required.

Project Details

Neuroblastoma is one of the major types of cancers affecting young children and arises from cells of the sympathetic nervous system. Three out of four of the members of the LIM domain only (LMO) family of transcription factors, i.e. LMO1, LMO3 and LMO4, have been implicated in neuroblastoma pathogenesis.

The LMO proteins are part of transcription factor complexes, where they function to bridge between different DNA binding transcription factors. Based on preliminary data, we hypothesize that LMO proteins are involved in the regulation of key genes during neuroblastoma development. Initially, this project will use human neuroblastoma cell lines to investigate the nature of these interactions. We will perform a number of molecular biology assays: (i) pull down assays to investigate which proteins participate in the protein complexes, (ii) chromatin immunoprecipitation assays, followed by genome-wide sequencing, to determine where these proteins are binding and which genes are regulated, and (iii) we will created shRNA constructs, which we will use to knock down LMO gene expression, in order to study the effect this has on cell proliferation and on binding of the protein complexes at their binding sites.

References

Wang K. et al. (2011) Nature 469, 216-220
Ferronha et al. (2013) J. Neurosc. 33, 2773-2783
Aoyama et al. (2005) Cancer Res. 65, 4587-4597

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