Regulation of Inflammasome Function by the Ubiquitin System
Supervisors:
Dr Ben Collins, School of Biological Sciences (Queen's University Belfast)
Prof Helen Walden, School of Molecular Biosciences (University of Glasgow)
Dr Rebecca Coll, Wellcome-Wolfson Institute for Experimental Medicine (Queen's University Belfast)
Summary:
Inflammasomes are intracellular protein complexes that sense microbial- and host-derived stress signals and promote cytokine release and inflammatory cell death (pyroptosis). They have emerged as key mediators of inflammation, however, we are far from a complete understanding of inflammasome functional regulation. The activity of inflammasomes has been reported to depend on various post translational modifications (PTMs) including ubiquitination but this aspect is yet to be systematically evaluated.
We will use a combination of quantitative mass spectrometry-based proteomics, computational biology, structural biology, biochemistry, immunology, cell biology to achieve the following project aims:
1) Generate a global proteomic profile ubiquitin activity system in activated cells
2) Determine ubiquitin modification state of proteins in activation of inflammasomes
3) Characterize the functional consequences on inflammasome activity of perturbing/removing various components of the ubiquitin system
4) Structural characterization of implicated ubiquitin regulatory complexes
The expected outcomes of the project will be insight into the molecular mechanism and functional role of ubiquitination in inflammasome biology.
To carry out this interdisciplinary project the successful candidate will join the Collins, Walden, and Coll research teams at QUB and UoG benefitting from state-of-the-art technology and training in a variety of research areas quantitative mass spectrometry, computational biology, structural biology, biochemistry, immunology, cell biology. The student will also receive support to develop essential research skills, project management, scientific writing/communication, and innovation.