Project Reference: TRG27-PAT-JS1

Project title: Mathematical and computational methods to discover and characterise critical genetic features in RNA viruses, with application to Rift Valley Fever Virus

Project outline

Population growth and climate change have increased the risk of viruses spreading into new habitats and new hosts. The drivers of virus life cycles are incompletely understood, so new techniques to interrogate genetic data from these viruses can provide important biological insight. Genetic analysis can also help understanding as-yet unknown viruses as they emerge. An example of a virus with risk of global spread is Rift Valley Fever Virus, a mosquito-borne virus endemic to Africa and Arabia capable of causing outbreaks in livestock and occasionally humans.

This project will focus on developing mathematical and computational biology methods to analyse genetic data from virus sequences, to find and characterise signals of evolutionary constraint and predict the contributions made to the virus lifecycle by genomic regions under such constraint. Signals of evolutionary constraint take different forms, and a major goal of this project is to move from current generic approaches for finding constraint, to approaches tailored to the different forms of constraint seen (e.g. from molecular structure or protein coding requirements), in order to predict better these features’ biological importance.

The project will use the languages of probability and statistics, computationally applied to model and understand different evolutionary constraints in a highly-adapted vector-borne virus with multiple host species. There will be the opportunity to learn how the virus operates at the molecular level, make comparative analyses with related viruses, and to place the virus into the broader context of its socioeconomic impact.

The project will move from methods development to proof-of-concept application, with concrete biological predictions as outcomes.

The studentship will provide training in statistical analysis applied to biological systems, at the interdisciplinary interface between mathematics and the biology of RNA structure/function in viruses.

Principal Supervisor

Dr Jordan Skittrall

Email address: jps55@cam.ac.uk

Department / Partner Institute: Pathology

Website: https://skittrallgroup.org/

BBSRC strategic theme

Understanding the rules of life