PhD Studentship: Uncovering the mechanism of minor spliceosome autoimmune diabetes

Overview

This PhD studentship focuses on uncovering the mechanism of minor spliceosome autoimmune diabetes. Inherited changes in two core minor spliceosome components, RNU4ATAC and RNU6ATAC, cause a monogenic form of autoimmune diabetes where the immune system destroys insulin-producing beta cells in the pancreas. Although the minor splicing machinery is present in every cell, its failure leads to a specific immune attack on pancreatic beta cells. The project investigates which incorrectly spliced U12-intron genes drive the immune system to attack beta cells and how this occurs.

Who can apply

Applicants are welcome from biological, biomedical, computational, mathematical, or data science backgrounds. Full training will be provided in unfamiliar areas.

What you get

The studentship funding provides Home tuition fees and a Doctoral Stipend for up to four years, with a salary listed as £0 per annum. The position is full-time and fixed-term.

Requirements

The project involves developing a computational framework to rank U12-intron genes, confirming missplicing in patient cells, and switching off a shortlist of genes in cell models to test effects on immune activation, tolerance, antigen presentation, cell stress, and survival. The research methodology progresses from prioritizing candidate genes using public and patient data in the first year, to measuring intron retention and establishing cell models in the second year, performing gene knockdowns or knockouts in years two through three, and integrating findings, publishing data, and submitting a thesis in the final year.

Key dates

The closing date for applications is 2027-01-05.