Virulence strategies for Mycobacterial persistence: Investigating the role of the Mammalian Cell entry proteins. (360G-Wellcome-207495_Z_17_Z)

£99,951

The global burden of mycobacterial infections especially tuberculosis is inconceivable with at least one new case of infection arising every second, every third person being latently infected and around 2 million people dying annually. Persistence of mycobacteria arises from long durations of dormancy within host macrophages evading host defense mechanisms and utilising unusual nutrients. Mycobacterial Mce (Mammalian cell entry) transport systems play an important role in facilitating cell entry and import of nutrients like cholesterol or lipid. This proposal concentrates on characterizing the Mce4 proteins and their assembly in the Mce4 transport system. One of the key goals is to isolate a minimal hetero-complex of the Mce proteins forming the transport channel for structural and functional studies. Two possible models for organisation are proposed: i) a heterohexamer of six Mce proteins or ii) a stack of six homo-hexamers of individual Mce proteins. Biochemical characterisation of individual Mce proteins and interaction studies between different Mce proteins will help establish the organisation model of Mce4 proteins. Structural studies using X-ray crystallography or other techniques, and functional characterisation for cholesterol binding and cell invasion will shed light on the structure-function relationship of Mce4 proteins within the transport assembly.

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Grant Details

Amount Awarded 99951
Applicant Surname Darbari
Approval Committee Science Seeds Advisory Panel
Award Date 2017-05-12T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title Seed Award in Science
Internal ID 207495/Z/17/Z
Lead Applicant Dr Vidya Chandran Darbari
Partnership Value 99951
Planned Dates: End Date 2019-11-01T00:00:00+00:00
Planned Dates: Start Date 2017-11-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London