Faraday earmarked proposal: Toll-like receptors and dendritic cell genetic heterogeneity
Lead Research Organisation:
University of Edinburgh
Department Name: The Roslin Institute
Abstract
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Technical Summary
Improvement in the efficacy of vaccines and the identification of genetic traits affecting disease resistance will have a large impact on disease control in livestock. Many current vaccines are live vaccines with limited long term protection. Variable responsiveness to vaccines has been observed across populations and includes non-responsiveness as well as pathogenic responses. Disease resistance traits are also highly variable both between and within breeds. Variability in both vaccine responsiveness and disease resistance traits can have moderate to high heritability and the genes underlying these traits are likely to overlap, and involve both Major Histocompatibility Complex (MHC) and non-MHC genes. Major goals for the UK pharmaceutical and breeding industries would be to create uniformly efficacious non-live subunit vaccines for livestock and identify suitable markers for breeding for disease resistance and vaccine responsiveness. Our contention is that there will be genes underlying these traits that are expressed in the innate immune system. Specifically, this proposal will concentrate on the expression, function and polymorphism of pathogen- recognition receptors (PRR), specifically the toll-like receptors (TLR) found on authentic dendritic cells (DC) derived from cattle and sheep afferent lymph. These cells are a major component of the innate immune system and form an instructive link between the innate and acquired (adaptive, antigen-specific lymphocyte-mediated) immune systems.
Organisations
Publications
Jann, O
(2008)
Comparative genomics of Toll-like receptor signalling reveals candidate genes for disease resistance traits
in 31st Conference of the International Society of Animal Genetics
Jann, O
(2008)
A phylogenetic approach to identify substitutions of functional relevance in bovine Toll-like receptor 2
in 3rd International Symposium on Animal Functional Genomics (ISAFG)
Leach, R
(2010)
Locating SNPs in the bovine genome associated with variation in the immune response
in 9th World Congress on Genetics Applied to Livestock Production
Leach, R
(2010)
Fine mapping the genetic component of the immune response to a 40-mer peptide derived from a foot-and-mouth-disease virus
in AVTRW 2010 Conference
Smith SA
(2012)
Adaptive evolution of Toll-like receptor 5 in domesticated mammals.
in BMC evolutionary biology
Jann OC
(2008)
Molecular evolution of bovine Toll-like receptor 2 suggests substitutions of functional relevance.
in BMC evolutionary biology
Jann OC
(2009)
Comparative genomics of Toll-like receptor signalling in five species.
in BMC genomics
Glass, E
(2010)
The genetics of immune and vaccine responses in cattle
in Conference on Molecular and population genetics for improvement of farm animals and their products
Yamakawa Y
(2008)
Identification and functional characterization of a bovine orthologue to DC-SIGN
in Journal of Leukocyte Biology
Bovine Genome Sequencing And Analysis Consortium
(2009)
The genome sequence of taurine cattle: a window to ruminant biology and evolution.
in Science (New York, N.Y.)