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Sialic acid, a sugar first discovered eighty years ago, has proven to be a vitally important molecule in the interplay between our cells and the pathogens and commensal bacteria that endeavour to make us their home. The student will contribute to projects in our group that investigate the interactions between these sugars and proteins expressed by medically relevant bacteria.
In particular H. influenzae, which is responsible for a wide range of medical conditions. H. influenzae is a frequent co-conspirator with other pathogens, with correspondingly increased associated mortality. In H. influenzae sialic acid is transported by an unusual family of membrane protein complexes that are, as of yet, uncharacterised by structural means. This system is an important component of its survival toolbox. Once scavenged and imported, the sugar is presented on the bacterial cell surface, appearing to the immune system as self by mimicking our own cells’ extensive sialylation. In its absence, H. influenzae is unable to survive exposure to human serum and has a reduced capacity to produce biofilm, making the transporter an attractive drug target.
The student will investigate the expression and purification of this challenging system, and once optimal parameters are identified, will perform crystallisation experiments. Data generated from this project will feed into efforts to develop novel antibacterial agents. The student will also contribute to ongoing projects involving bacterial carbohydrate binding proteins. These will provide additional opportunities to gain experience in the later stages of the structural biology pipeline, including the preparation of sample grids for analysis by cryo electron microscopy and the collection of X-ray diffraction data.
Suitable Subjects: Biology, Chemistry
Project duration: 12 weeks
TO APPLY PLEASE FOLLOW THE LINK BELOW
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