Division: Systems Medicine
Start date: 20/09/21
Ion channels represent potential novel targets for the development of personalised colon cancer drugs. Prime examples are the voltage-activated sodium ion (Na+) channels (VASCs) known for their role in generating action potentials in excitable cells. Surprisingly, some human tumours and cell lines, including colon cancer cells, express VASCs not seen in non-malignant epithelial cells. Importantly, rodent colon cancers do not express VASCs and this creates a challenge in understanding their roles in disease development. NaV1.5 activity in human metastatic colon cancer cells enhances invasion. Knock down of NaV1.5 expression or inhibition by local anaesthetics (LAs) and other drugs reduces invasion. VASCs are particularly attractive targets because there are several approved drugs, including LAs, which may be repurposed as novel colon cancer treatments. However, the role of NaV1.5 in the activity of the primary tumour is not understood. Innovative model systems are required to improve translational success of preclinical studies – one such innovation is human tumour-derived organoid cultures. These possess spatially restricted lineage commitment and higher-order self-assembly, which recapitulates key physiological features.
By combining the colon cancer organoid model with electrophysiological recording techniques we will establish a novel approach to assessing the roles of ion channels in human colorectal cancer tumorigenicity. We will establish the potential of ion channels, transporters and neurotransmitter receptors expressed by colon cancer cells as prognostic indicators and targets for developing new therapeutic approaches.
Applicants to complete the Application form and email to [Email Address Removed] along with a CV and 2 academic references by Monday 22nd March 2021.
First class honours degree, and/or a Masters degree in a relevant discipline. (Non-clinical applicants)
MBChB (clinical applicants)
English language requirements
IELTS minimum overall score of 6.5
Reading 5.5, Listening 5.5, Speaking 5.5 Writing 6.0