Comparative and functional biology of Toll-like receptors in vertebrates

Lead Research Organisation: University of Oxford
Department Name: Interdisciplinary Bioscience DTP

Abstract

The Toll-like receptors represent the first line of detection of a pathogen challenge, and are thus crucial for the initiation of the immune response. They respond to a variety of highly conserved microbial- and damage-associated molecular motifs that are associated with pathogen presence. The overall aim of this project is to examine how Toll-like receptors have evolved to cope with different pathogen pressures. Animals inhabiting vastly different environments, and in different population structures, are under diverse selective pressures to adequately respond to microbial threats. Furthermore, animals under artificial selection - such as those reared for the food industry - have undergone recent, strong selective sweeps that are likely to have impacted the immune system. This project aims to understand the evolutionary changes in TLRs using a comparative approach, making use of both bioinformatic and functional analyses.

BBSRC Priority Areas:
A better understanding of the innate immune system has important implications for animal health and welfare, and protection of a sustainable food chain. The applications of this work are potentially far-reaching, and could impact wild and farmed animals. For instance, optimisation of vaccine adjuvants - which rely on innate immune stimulation - could result in the development of more effective, safer vaccines. Furthermore, using a comparative approach, polymorphisms in TLR genes could be identified that render animals susceptible to certain pathogens, which could also directly impact animal wellbeing in the food industry.

WUB, ENWW

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011224/1 30/09/2015 29/09/2023
1757837 Studentship BB/M011224/1 30/09/2016 28/09/2021 Steven Robert Fiddaman
 
Description Animals living in different environments are subject to differences in the diseases they encounter. The Toll-like receptors are the first line of defence in detecting pathogen challenge, and have been shown to be crucial for initiating an immune response that ultimately leads to the clearance of a pathogen.

I have shown that there is a substantial amount of TLR diversity between species, and that this is functionally relevant. This is likely to be a consequence of the different pathogen selective pressures acting upon different species. I have also demonstrated that functional TLR diversity exists at the sub-species level in a species with a very large (and environmentally heterogeneous) spatial distribution. Furthermore, I have also shown that TLR diversity differs over time in the same species, through the use of ancient samples.
Exploitation Route Immunogenetics studies can be useful indicators of selection pressures acting on different species. Understanding of the host response to infection can lead to better vaccine adjuvants, as well as identification of host variants that are associated with resistance or susceptibility to a particular disease.
Sectors Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology