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Proteolytic network regulating the human innate immune response


Department of Biology

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Dr D Boucher , Prof I Hitchcock No more applications being accepted Self-Funded PhD Students Only

About the Project

The innate immune system is our first line of defence against a wide range of bacteria and viruses. Upon infection, immune cells, such as macrophages and neutrophils, will assemble signalling platforms termed inflammasome, to restrict and clear the insult. Inflammasomes enable the activation of cysteine proteases, called inflammatory caspases. When activated, caspases enable the secretion of pro-inflammatory cytokines (e.g. IL-1 and IL-18) and a highly inflammatory form of cell death called pyroptosis. Immune cells activate inflammatory caspases through two types of inflammasomes: the canonical inflammasome, responsible for the activation of caspase-1, and the non-canonical inflammasome, which activate caspase-11 in mice or caspase-4 and -5 in humans. Inflammatory caspases are important components of our immune system and are essential to respond properly to infection. However, inappropriate activity of those enzymes is involved in fatal conditions like sepsis. The new knowledge generated by this project will provide an essential understanding of the human innate immune system and potentially leads to new therapies that will either enhance the response toward pathogens or restrict caspase activation during life-threatening conditions. Our knowledge of inflammasome signaling is mostly based on studied performed in mouse. This project aims to better understand inflammasome signaling in human and the role of inflammatory caspases, addressing an important knowledge gap.


The successful candidate will work in the newly-establish lab of Dr Dave Boucher and collaborate with the lab of Pr. Ian Hitchcock and other labs at the University of York.

This multidisciplinary project offers a unique opportunity to get hands-on training on a wide range of cutting-edge biochemical (protein expression, enzymology) cellular (isolation of primary cells, Crispr Cas9) and immunological approaches (cell death assay, Elisa) to provide key knowledge of our immune system.

Funding Notes

This is a self-funded project. Applicants need to have adequate funds to meet the costs of a self-funded research project including tuition fees and living expenses for the duration of the research programme. Please see information on tuition fee costs, living expenses and funding opportunities.

References

Applications are welcome for either for a 1-year MSc by Research or for a 3-year PhD.


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