Splicing regulation in meiosis: characterising the role of a conserved RNA binding protein

Current trends in gene expression analyses are multidisciplinary, and lean heavily on both molecular analyses and data driven biology. In this project the student will be trained by experts in both, to analyse RNA processing patterns at a global "-omics" level, along with detailed follow up of key individual targets. The molecular biology will be taught by the Newcastle group (Institute of Genetic Medicine, Newcastle University). The bioinformatics will be taught by the Durham group (Dr Sushma Grellscheid, Department of Biology, Durham University). Infertility affects many couples, but the reasons causing it are usually unknown. This project will analyse an RNA binding protein that has been identified as mutated or deleted in infertile men, yet is so far very poorly understood. This project will include world class training in both molecular biology and bioinformatics which will place the student in a strong place in the jobs market.

Meiosis is the specialised cell division programme that makes sperm and eggs. This project will build on resources generated by a recently awarded BBSRC want to comprehensively analyse an RNA binding protein that is expressed only in meiosis and implicated in male infertility. We have discovered using RNAseq of wild type and knockout mice that this RNA binding protein controls nuclear RNA processing during male meiosis. Most surprisingly, this includes preventing regions of intron being mistakenly included into mRNAs which leads to poisoning of the meiotic transcriptome. It is not known how hnRNP GT functions. This PhD project will test the hypothesis that this RNA binding protein controls splicing of these sequences either by direct RNA interactions, or by interacting with other splicing regulators. This is important, as mice containing this knockout arrest sperm development in meiosis and are infertile.