Structural and biochemical studies on Notch signal transduction

Structural and biochemical studies on Notch signal transduction

Project details

The Notch signalling pathway is essential for development and homeostasis of all animals and is frequently mutated in cancer. Notch signal transduction begins with the binding of ligand to the extracellular domain of the Notch receptor. This initiates a series of proteolytic events that result in the translocation of the intracellular domain of the receptor to the nucleus and transcription of Notch target genes.

This project will combine structural and cell biology approaches to investigate Notch signal transduction.

A range of techniques are available including recombinant protein production and purification, X-ray crystallography, receptor analysis, cancer organoid assays and anticancer assays with Notch inhibitors.

For background information we recommend the review: Andersson, ER et al., Notch signaling: simplicity in design, versatility in function, Development 138, pp3593-3612(2011)

About our research group

The Notch signalling pathway is de-regulated in numerous cancers including leukaemia, breast cancer, head and neck cancer, and colon cancer, which are amongst the most prevalent forms of cancer.

In our team, structural biologists, cell biologists, students and cancer clinicians work together towards producing Notch inhibitors for treating cancer.

We aim to understand the molecular mechanisms of Notch signal transduction and how we might interfere with Notch signalling to develop improved treatments for Notch-driven tumours, both broadly and in the context of colon and head and neck cancers.

We have recently solved the structure of the Notch ligand Delta-like 1 (Kershaw et al. Biochemical Journal  468  p159-166 2015). We use X-ray crystallography to determine the details of the Notch-receptor/ligand interactions to empower the development of specific inhibitors of Notch signaling.

Researchers:

Nadia Kershaw profile
Dr
Nadia
Kershaw
Structural Biology division

Project Type: