Mots-Clés

Membrane protein, channel, 3D structure, prediction, molecular dynamics, potential of mean force

Description

Understanding impact of mutations in KCNQ1 channel and their role in tumor progression using computational biophysics approaches.

This project supported by INCA is an interdisciplinary project that aims to understand how somatic mutations carried by ion channel-encoding genes participate in tumour progression by altering associated signalling pathways. It is conducted in partnership with electrophysiologists and pathophysiologists. 

Context: The potassium channel KCNQ1 was characterised as a gatekeeper of colonic epithelial integrity acting through the restriction of Wnt/ β-catenin signalling pathway. Aberrant activation of this intracellular signalling pathway is the main driving force for colorectal carcinogenesis. Several mutations on the KCNQ1 gene were identified in colon cancer databases.us, it is hypothesized that colorectal cancer (CRC)-associated mutations carried by KCNQ1 promote Wnt signalling activity and participate in CRC pathophysiology. Therefore, the present consortium aims at i) defining how each CRC-associated KCNQ1 mutation affects the channel structure-function relationships and biophysical properties and ii) understanding the effects of representative CRC-associated KCNQ1 mutations on the Wnt signalling activity. 

The post-doc will be in charge of:

• Predicting how CRC-associated KCNQ1 mutations affect the channel structure using bioinformatics and computational biophysics methods. 
• Studying the interaction between KCNQ1 and b-catenin: