Development of novel therapies for Hirschsprung’s Disease

Description

As a PhD student, you'll be part of a groundbreaking project aiming to revolutionise the treatment landscape for Hirschsprung's Disease (HSCR). HSCR affects around 170 infants annually in the UK, and is caused by aganglionosis of the bowel due to the abnormal development of the enteric nervous system (ENS). The conventional treatment involves surgical intervention, but can result in long-term complications, impacting the quality of life for affected children.

This research focuses on understanding the developmental mechanisms underlying HSCR and exploring non-surgical alternatives by leveraging neurospheres derived from aganglionic and ganglionic bowel tissue of children undergoing surgery to treat this condition. This is an exciting opportunity to be involved in a translational regenerative medicine project for a condition that has a significant impact on the lives of the children who are affected by it.

The successful candidate will have the opportunity to study within a team which is supervised by both academic and clinical experts in the field and who have had a successful collaboration in Hirschsprung’s Disease for over 20 years. The candidate will be supported through regular supervisory meetings and one-on-one teaching on laboratory techniques. They will be working with other students also interested in regenerative medicine therapies and will be invited to attend and present at laboratory meetings.

Responsibilities

Within this project the successful candidate will be expected to undertake the following experimental streams:

Experimental Design and Analysis: Consent families to participation in the study and follow GCP regulations around study procedures, collect bowel specimens from infants undergoing surgery, culture neurospheres using established protocols, expose them to agonists and antagonists, and perform rigorous analysis using immunohistochemical markers, confocal microscopy, and proliferation assays.

Neurosphere Comparative Analysis: Comparative studies will be undertaken on neurospheres cultured from ganglionic, aganglionic, and control bowel specimens to understand the composition, characteristics, proliferation rates, and differentiation potential of ENS and Schwann Cell Progenitor (SCP) cells.

Investigate Regulatory Factors: Explore the effects of serotonin, Endothelin 3 (EDN3), and Notch signaling pathways on neural cell proliferation and differentiation in neurospheres derived from HSCR and control bowel tissue.

Documentation and Communication: Document experimental procedures, results, and observations meticulously. Present findings internationally, publish in peer-reviewed journals, and actively engage in educational events, online resources, and social media platforms to disseminate research outcomes.

To apply, send a copy of your CV (with a cover letter) to Rachel.Harwood@alderhey.nhs.uk. The expected start date for this project is September 2024.