Development of a proteomics platform to monitor immune responses in non-mammals.

From early studies of bacterial phagocytosis by sea urchin cells, to the more recent discoveries of B and T cells in chickens or toll-like receptors (TLRs) in fruit flies, the study of immune responses in 'non-traditional' species has greatly enhanced our understanding of the human immune system. While the recent explosion in genomic and transcriptomic sequence data has greatly aided the discovery of orthologues of mammalian immune genes in such species, allowing us to trace their evolutionary histories, our ability to perform functional studies remains limited by to a lack of research reagents (e.g. monoclonal antibodies). In an effort to leap-frog this hurdle we are developing a proteomics platform that will allow researchers to study immune responses in any species where sufficient sequence data is available. The project will involve optimisation of our new platform and assessment of its ability to measure the levels of selected immune proteins in non-mammalian species over the course of an immune response.

Much of our work to date has focused upon the immune system of cartilaginous fishes (sharks, skates, rays and chimera); this group diverged from a common ancestor with other jawed vertebrates around 500 million years ago and are the most ancient species to have a 'mammalian-like' adaptive immune system. As part of an ongoing project we have recently generated a high-coverage, multi-tissue transcriptome for the small-spotted catshark (Scyliorhinus canicula) and are actively mining this dataset for families of immune genes. This places us in a perfect position to assess the 'real-world' utility of our proteomic platform by studying the immune response of immunised catsharks. The project will be extended to additional non-mammalian species either by mining datasets that are already publically-available or following the generation of a transcriptome for a new species.

The student will receive training in standard molecular biology techniques, bioinformatics, in vivo study design and implementation, as well as various immunological assays and techniques. Project-specific proteomics training will be provided through Aberdeen University's Proteomics facility. Training in next-generation sequencing and bioinformatics is available through the recently-established Centre for Genome-Enabled Biology & Medicine (CGEBM). Additional training in generic skills is provided by the CLSM graduate school and the University's Centre for Academic Development.

Achievement of this project will improve our ability to study immune responses in species where functional studies are currently limited by a lack of research reagents. As well as increasing fundamental knowledge regarding the evolution and functioning of the immune system, other potential future applications are diverse and include development of new/improved vaccines for animal health, studying zoonotic infections and host immunity for the protection of human health, and the rapid diagnosis of infectious disease in non-human species.