Understanding Colorectal Cancer risk loci that alter transcriptional dynamics

This is one of several projects available on a CRUK funded PhD programme at the Cancer Research UK Edinburgh Centre, which is part of the Institute of Genetics and Molecular Medicine (IGMM) at the University of Edinburgh.

Project details

This project will investigate candidate colorectal cancer (CRC) risk genes in model systems, to determine and understand their cellular role and how they are involved in cancer risk and progression.

The 11q23 locus was identified in a 2008 genome wide association study as being a CRC risk locus (Tenesa*, Farrington* et al. Nature Genetics). The three genes within the locus – C11orf53, COLCA1 and COLCA2 – have also been shown to be eQTLs (expression quantitative trait loci) for the tagging risk SNP in human colonic normal epithelium.

The function of these genes and their possible role in CRC remains enigmatic. We are therefore generating a number of model systems using both CRISPR technology and conditional trans-gene approaches, to allow us to gain insight into which genes play a role in CRC and their mechanism of action.

Aims
Investigate these genes of unknown function utilising the different model systems and lines to assess the impact of these genes on transcriptional and proteomic landscapes.

Explore links of this gene region with inflammation and other environmental influences, and the impact on CRC initiation and progression.

Interrogate any intestinal or other phenotypes, which may aid in understanding the function of the genes and be utilised to explore the role of the genes in CRC and intestinal development and ultimately aid in prevention, screening and therapy of CRC.

The successful applicant will join a multi-disciplinary team of dedicated researchers including surgeons, bio-statisticians and bio-informaticians who are striving to identify, understand and modify colorectal cancer risk factors, using large scale system genetics/biology approaches.

Hence they will receive expert training in phenotyping, genomic data generation and analysis (imaging, proteomics, transcriptomics and their analysis, including the use of R and other bioinformatics approaches). A number of model systems are already generated and therefore the project will begin to generate invaluable data from the start.

www.ed.ac.uk/cancer-centre/research/farrington-group/colorectal-cancer-genetics

For further information on how to apply for this project, please visit: https://www.ed.ac.uk/cancer-centre/study-with-us/cancer-research-uk-phd-programme