Understanding the immunoprotective function of the adenosine deaminase acting on RNA-2
Supervisors:
Dr Aikaterini Gatsiou, Faculty of Health and Medicine (Lancaster University)
Prof Helen Walden, School of Molecular Biosciences (University of Glasgow)
Summary:
Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by ADAR proteins, is the most abundant cell-intrinsic RNA nucleotide change playing a crucial role in regulating immune responses. While ADAR1 is essential for survival, recent evidence suggests that ADAR2 selectively modulates immune cell trafficking during stress, without compromising blood vessel integrity. This makes ADAR2 an exciting therapeutic target.
This project will offer insights into ADAR2 and its interactions with immune-associated double-stranded RNAs. Using advanced techniques like RNA-protein interaction assays, RNA modification, mapping and detection assays, cryo-EM and AI-based 3D structure prediction, we aim to characterize the molecular determinants underpinning ADAR2's role in a fundamental biological process, the immune cell trafficking.
The successful candidate will gain expertise in protein biochemistry, structural biology, RNA biology, and cutting-edge imaging techniques. This project has the potential to uncover novel therapeutic pathways in immune regulation with applications in cancer and inflammatory diseases.
This PhD will suit students interested in molecular biology, immunology, big data, and drug development.