Investigating the Role of Aberrant cellular signaling and RNA processing in male infertility

Department: Institute of Genetics and Cancer

Number of current Students: 0

Completed Supervisor training: Completed

Co Supervisors: Professor Sarah Martins Da Silva, University of Dundee, s.martinsdasilva@dundee.ac.uk / Dr Alexandra Martin-Geary, University of Edinburgh, Alex.geary@ed.ac.uk / Dr Margot Wyrwoll, University of Edinburgh, Margot.Wyrwoll@ed.ac.uk

Infertility affects roughly 1 in 7 couples, with rising rates of infertility constituting a slow-moving health emergency. Infertility is a contributing factor in a trend towards ageing populations which is an emerging global health challenge. In approximately half of cases, infertility is found to be caused by male reproductive issues. Despite this, research addressing the genetic underpinnings of male infertility lags behind other fields.

About the project :

Testes are one of the most biologically diverse organs in the human body, requiring a dynamic interplay of Cellular signalling and RNA processing to maintain proper function. However, the role of genetic regulation in these processes is incompletely understood. This project will investigate the role of non-coding RNAs (ncRNAs) in sperm development and function, specifically focusing on those involved in CatSper signalling (Prof. Sarah Martins Da Silva, Dundee), and splicing (Prof Joris Veltman, Edinburgh). Combining unique in-house data comprising short- and long-read whole-genome sequencing from a large cohort of infertile men, alongside population scale publicly available data you will map the landscape of genetic variation across spliceosomal and CatSper interacting ncRNAs.You will leverage existing and novel state-of-the-art computational tools and methods, combined with a deep understanding of the mechanisms of human disease, to predict the impact of genetic variants in ncRNAs. You will identify ncRNAs involved in the regulation of these processes, elucidate their functions and determine how their disruption contributes to disease. 

The core aims of this project are to: 

• Identify key regulators of RNA processing and calcium signalling. 
• Determine the contribution of disruption of these regulators to male infertility. 
• Identify new biomarkers that can be used in diagnostics and as targets for the development of therapeutic interventions

• Oud, M.S., et al. A de novo paradigm for male infertility. Nat Commun 13 (2022). 
• Brown, S. G., et al Complex CatSper-dependent and independent [Ca2+]i signalling in human spermatozoa induced by follicular fluid. Hum. Repro. 32(10) (2017)
• Wyrwoll, M., Tüttleman, F., Reproduction, genetics, and health – a topic with implications far beyond infertility Med Genet. 36 (2024). 
• Chen, Y., et al. De novo variants in the RNU4-2snRNA cause a frequent neurodevelopmental syndrome. Nature 632 (2024). 
• Yan, Q. and Wang, Q. Exploring the Characters of Non-Coding RNAs in Spermatogenesis and Male Infertility. Int. J. Mol. Sci. 6(3) (2025).
• Ghafouri-Fard, S. et al The Interaction Between Non-Coding RNAs and Calcium Binding Proteins. Front Oncol. 4 (2022)

BBSRC Remit Area: Bioscience for an Integrated Understanding of Health