Cell-type specific RNA Processing Defects in Neurodegeneration

About the project

About the Project PhD only Summary Neurodegenerative diseases such as Parkinson’s disease, Lewy body dementia and Alzheimer’s disease are associated with profound changes in vulnerable cell populations in the human brain. However, we still understand relatively little about how disease alters RNA processing within specific cell types, or how these changes contribute to neuronal dysfunction, disease progression and therapeutic vulnerability. This PhD project will use human brain transcriptomic data, including single-nucleus, spatial, short-read and long-read RNA sequencing, to identify disease-associated changes in RNA splicing, transcript isoform use, RNA editing and 3′ untranslated region usage. The student will integrate transcriptomic data with genetic and cellular information to identify RNA-processing events and RNA-binding proteins that may contribute to neurodegeneration. Depending on the student’s interests and skills, the project may include computational analysis, development of reproducible pipelines, and experimental validation in human tissue or iPSC-derived cellular models. Project Aims To identify cell-type specific changes in RNA processing in human neurodegenerative disease brain tissue. To determine how changes in splicing, transcript usage, RNA editing and untranslated region usage relate to disease state, cell identity and genetic risk. To prioritise candidate RNA-binding proteins, transcript isoforms or RNA-processing events that may represent biomarkers or therapeutic targets. To validate selected candidates using independent datasets and, where appropriate, human cellular models or tissue-based assays. https://www.ukdri.ac.uk/labs/ryten-lab How to Apply; If you are interested in this project, please go to the University pages and apply via the online portal; PhD https://www.postgraduate.study.cam.ac.uk/courses/directory/cvcnpdpcn/apply

Research areas