Project No. 2109

Primary Supervisor

Prof. Nullin Divecha – University of Southampton

Co-Supervisor(s)

Prof. Anastasia Callaghan – University of Portsmouth

Summary

The biology of RNA involves its transcription, modification, maturation, export to the cytoplasm, trafficking to various intracellular compartments, translation and degradation. Control of these complex processes, involves a panel of protein domains, specifically interacting with structural features of RNA.

Additionally, environmental cues regulate the interaction of these domains with RNA to impact on cell fates such as migration, proliferation, survival, and differentiation. These cues often regulate polyphosphoinositide (PPIn) signalling. PPIns are a family of seven phosphorylated lipid messengers, whose levels are controlled by the balance of the activities of PPIns lipid kinases and phosphatases. Changes in the levels of PPIns generates new and unique membrane surfaces which interact with, and recruit, key protein components through PPIn-interaction domains. Binding to PPIns modulates the cognate protein’s localisation, activity or interaction partners to control downstream cellular processes.

With dysregulation associated with cancer, inflammatory responses and neurodegeneration, identifying new protein domains that interact with PPIns will reveal novel mechanisms of relevance to health and disease. Excitingly, recent discoveries have identified that specific RNA binding motifs interact with PPIns (Divecha). Importantly, a newly developed functional-RNA array technology is now available to support broad RNA-interaction studies in highthroughput (Callaghan), providing a key enabler for exploring RNA-RNA binding motifs-PPIns interactions guided by, or to inform, cellular studies. The challenge for the PhD student will be to combine the novel RNA array technology and state-of-the-art biophysical molecular interaction approaches (Callaghan lab) with cellular biology and signalling technologies (Divecha) to reveal how PPIns/RNA binding motifs/RNA interactions modulate specific aspects of RNA biology.

We expect the student to develop expertise in:

• RNA, RNA binding motifs, PPIns and their interactions
• Biophysical and structural techniques; including application of the novel RNA array technology
• High definition cell microscopy
• CRISPR-CAS9 mediated gene editing
• Large data bioinformatic analysis