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Adaptive immune modulation by aldehydic protein adducts

Sir William Dunn School of Pathology

Prof Q Sattentau Friday, January 08, 2021 Competition Funded PhD Project (Students Worldwide)

About the Project

Aldehydic groups are non-enzymatically adducted to proteins under diverse physiological conditions including during inflammation. These aldehydic modifications enhance the immunogenicity of adducted proteins, driving a robust, class-switched antibody response in the absence of extrinsic adjuvants. This finding has direct relevance both to antibody-based vaccine design, and to immune disorders linked to inflammation such as autoimmunity. In this latter respect we have recently demonstrated that aldehyde adduction is sufficient to break tolerance to self-protein. We have shown that B cell responses are specifically enhanced by aldehydic adducts, and that their activation correlates strongly with complement deposition onto the modified protein. We now wish to further probe the implication of complement in B cell activation, and define how this might contribute to immune enhancement. This project is strongly interdisciplinary, and will involve biochemical analysis of protein modification using mass spectrometry and proteomics, probing of molecular pathways of complement-mediated B cell activation, and in vivo analyses of protein immunogenicity with relevance to disease models such as multiple sclerosis, and to antibody-based vaccine design.

Funding Notes

4 Year DPhil Prize Studentships cover full University fees, a tax free enhanced stipend of ~£17,285 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See View Website for full details and to apply.
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