A bacterial c-di-GMP responsive enzyme modulates LPS structure and triggers immune evasion (360G-Wellcome-203755_Z_16_A)

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Pseudomonas aerigunosa is a bacterial pathogen associated with acute and chronic infections in humans. The mode of infection by P. aeruginosa has been shown to depend on a small intracellular molecule produced by the bacterium, c-di-GMP, which is made by an enzyme called diguanylate cyclase (DGC). How c-di-GMP contributes to bacterial cell behaviour is not understood, but it is believed that a DGC transfers c-di-GMP to a receptor protein, thereby modulating its activity and capacitating the bacterium to develop a virulence trait. The Filloux lab has identified a DGC, SadC, which hands in c-di-GMP to a partner protein, called WarA. WarA shapes the surface of the bacterium, decorating it with a component called LPS. In absence of SadC and WarA, the surface is changed and the bacterium is quickly recognized by the immune system and eliminated. I aim to elucidate the WarA network and how it contributes to bacterial immune evasion in molecular details. I will use biochemical, genetic and genomic approaches or in vivo infection. Our understanding of the cascade of molecular events that lead to immune escape will then be used to screen for inhibitors that block the network and make P. aeruginosa susceptible to our immune system.

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Grant Details

Amount Awarded 0
Applicant Surname Glatzel
Approval Committee Internal Decision Panel
Award Date 2018-09-30T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title PhD Studentship (Basic)
Internal ID 203755/Z/16/A
Lead Applicant Miss Kira Glatzel
Partnership Value 0
Planned Dates: End Date 2021-04-01T00:00:00+00:00
Planned Dates: Start Date 2017-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London