Combining genetic and biophysical approaches to understand the structure function relationship of the Notch Abruptex domain

About the Project

Notch is a developmental signalling receptor with widespread roles in metazoan development and adult stem cell regulation. Precise control of Notch signalling levels is crucial for proper development and health. Inherited mutations of Notch are associated with genetic disease that involves misregulated development, and somatic mutations are linked to cancer. Understanding the link between genetics of Notch and its varied phenotypic outcomes is therefore important for developing novel therapeutic strategies. In our research we have identified a region of the Notch extracellular domain, outside of the ligand binding domain, where mutations cause altered endocytosis and upregulated signal activation. This project will combine genetic, biochemical and biophysical approaches to understand the mechanisms by which this region of Notch regulates its activity, using Drosophila Notch as an experimental model system. In particular, the student will examine how mutations affect structure and regulatory interactions of Notch, understand the mutant impact on Notch trafficking and signalling, and examine how disruption of function in this region leads to changes in gene expression networks. The work will combine biophysical techniques of NMR spectroscopy and crystallography to determine structure, biochemical methods of proximity biotin labelling to identify interacting partner proteins, and RNAseq experiments to understand the consequences of Notch mutations on the transcriptome.

Eligibility

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a biology-related subject. Candidates with experience in either Drosophila research, structural biology or biochemical approaches are encouraged to apply.

Before you Apply

Applicants mustmake direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

To be considered for this project you MUST submit a formal online application form – on the application form select PhD Developmental Biology Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester

If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester)

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 (high) fee. Details of our different fee bands can be found on our website: View Website