PhD studentship! Deadline Dec 11th 2024

Evolutionary mechanisms underlying differences in the innate immune response to infection

SWbio application link:
https://www.swbio.ac.uk/biomolecular-and-biophysical-studies/
For inquiries, please email: [email protected]

Based in:
University of Exeter, Penryn, Cornwall, UK.

Supervisory team:
Mark A. Hanson (University of Exeter, Penryn), primary
Ben Longdon (University of Exeter, Penryn), co-primary
Helen White-Cooper (Cardiff University)

Project description:

Host species vary markedly in susceptibility to infection. To understand how host shifts direct pathogen evolution, it is essential to understand how pathogens replicate in the face of varied host immune responses. Animal immune pathways are widely conserved, including Toll-like receptors regulating NF-κB immunity. However, the realised defence response of even closely related species can differ drastically. To understand why, this project will answer the following questions:

1. How does the induced immune response vary across host species to different pathogens? The student will utilize RNA sequencing and statistical models to assess similarities and differences of the induced immune response across a panel of host-pathogen infections.
2. How does immune pathway information flow vary across species? The student will use genetic and molecular biology techniques to disrupt immune pathways, studying species-specific effects on the immune response.
3. Which genes/processes drive differences in response to infection across species? The student will use phylogenetic mixed models, gene editing, and other molecular approaches to test what mechanisms govern differences in immune pathway activation.

The discovery of Toll-like receptors as immune molecules was first made in Drosophila melanogaster, and this model species boasts one of the best-described immune systems of any animal. Our work has previously characterised the survival and induced immune responses of 50+ Drosophila species using diverse infection biology and phylogenetic model approaches (Hanson et al. 2023; Science; Longdon et al., 2015; PLOS Path). The student will build on these prior works to reveal the genetic underpinnings of susceptibility to infection.

The student will receive training in RNAseq bioinformatic analysis, phylogenetic mixed models, molecular genetics, and evolutionary immunology. The supervisory team boasts expertise in immune evolution, genetics, and infection (Dr Mark Hanson), pathogen host shifts (Prof Ben Longdon), and non-model insect molecular biology (Prof Helen White-Cooper).

This project is part of the BBSRC priority lists of “Tackling Infections”  and “Integrated Understanding of Health.” Outcomes of this work will improve our understanding of why related species respond differently to the same infectious pathogens. As researchers studying insect vectors of disease look to Drosophila fruit flies as a model for immune system architecture, this work has clear application to understanding insect vector biology. More fundamentally, this work will inform on the evolutionary processes generating differences in the innate immune response to infection, which is critical for understanding future pathogen emergence.