Investigating the role of the spliceosome protein PRPF8 in cilia function

About the Project

Cilia are microscopic hair-like structures that protrude from the surface of almost every vertebrate cell-type, and are critical to numerous biological functions. There are motile cilia found on cells such as those of the respiratory tract, responsible for moving fluids around the cells. Additionally, primary cilia serve as sensors for signal transduction in and out of the cell. If the important functions of cilia are disrupted, it can lead to disease. The collection of diseases caused by cilia dysfunction are called ciliopathies.

There are multiple proteins that interact to form the cilium. Some proteins are required for the transport of cargo within the cilium, whereas others build up the three-dimensional specialised structure of the cilium. A recent discovery has shown that multiple proteins that are part of the pre-mRNA splicing machinery, termed the spliceosome, localise to the base of the cilium within the cytoplasm of cells. The functions that spliceosome proteins perform at the cilium are poorly understood. However, mutations in these specific spliceosome proteins cause retinitis pigmentosa, a disease that is linked to cilia defects, indicating that these proteins play an important role in the function of cilia.

In this project we seek to understand how spliceosome proteins are localised to the cilium and identify the roles these proteins have in cilia function. We will use bioinformatic analysis to search for putative cilia localisation signals within the protein sequences of spliceosome proteins known to localise to the cilia. We will use fish and mouse Prpf8 mutant models to investigate whether the roles of Prpf8 in the spliceosome and at the cilium are independent. These discoveries will further our understanding of the fundamental biological functions of cilia, as well as provide insights into diseases such as retinitis pigmentosa which are caused by cilia defects.

Candidates are expected to hold (or be about to obtain) a minimum 2:1 Bachelors Degree with Honours (or equivalent) in genetics, developmental biology, biomedical sciences, cell biology or biochemistry (or related subjects). Candidates with prior research experience in cilia biology or splicing factors are encouraged to apply.

Eligibility

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.

Before you Apply

Applicants must make 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 Genetics 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

References

Jiang F, Boylan M, Maxwell DW, Qureshi WMS, Rowlands CF, Tenin G, Mitchell K, Stephen LA, Vasconcelos EJR, Wang D, Chen T, Zha J, Liu J, Althali N, Leordean DV, Gallagher MT, Basu B, Szymanska K, Veeraghanta A, Keavney B, Humphries MJ, Ellingford J, Smith D, Johnson CA, O'Keefe RT, Roy S, Hentges KE. 2025. The RNA splicing factor PRPF8 is required for left-right organiser cilia function and determination of cardiac left-right asymmetry via regulation of Arl13b splicing. bioRxiv [Preprint]. May 27:2025.05.22.654869. doi: 10.1101/2025.05.22.654869. PMID: 40501629
Maxwell DW, O'Keefe RT, Roy S, Hentges KE. (2021) The role of splicing factors in retinitis pigmentosa: links to cilia. Biochem Soc Trans. 49(3):1221-1231.