Project Reference: ICS27-BIO-RS1

Project title: Uncovering rules of RNase H selectivity using AI

Project outline

RNase H is a unique enzyme that cleaves RNA component of an RNA:DNA heteroduplex. Cells need RNase H to get rid of persistent RNA:DNA hybrids that form during replication and transcription. Emerging therapeutic modalities such as Anti-Sense Oligonucleotide (ASOs) require RNase H for their activity. Thus understanding how RNase H selects its substrates is important for fundamental biology as well as biomedical research. The PhD project will leverage a new method we have developed using a large library of potential substrates to quantify the specificity of RNase H. The PhD project aims to generate experimental data on RNase H specificity using different chemical modifications and sequences of substrates.  The large-scale data will then be analysed using AI/ ML to predict principles that govern RNase H specificity. Predictions will be experimentally tested. The outcome of the project will be rules of RNase H activity which will allow designing ASOs for future therapeutic applications.

Principal Supervisor

Dr Ritwick Sawarkar

Email address: rs2099@cam.ac.uk

Department / Partner Institute: Biochemistry

Website: https://www.mrc-tox.cam.ac.uk/people/ritwick-sawarkar

Industrial Partner

AstraZeneca

BBSRC strategic theme

Transformative technologies