Structural and functional studies of regulatory assemblies and macromolecular machines. (360G-Wellcome-076846_Z_05_B)

£342,635

Many macromolecules in the cell function through multi-component assemblies whose activities can affect complex processes. We propose to study representative assemblies that play central roles in the regulation of gene expression and the coupling of metabolic pathways, and that comprise the machinery of transmembrane transport: Gene expression. Orchestrated turnover of mRNA is a key determinant of gene regulation. A critical role in regulating the balance and composition of mRNA transcripts is played by the multi-component RNA degradosome in Escherichia coli, effecting the coordinated expression of many genes from diverse metabolic pathways. We have solved several structures of the degradosome components and are investigating their interactions. We will study the structure and function of the complete assembly and of the analogous exosome, to explore how the machinery has evolved to meet the requirements of an expanded genome. Metabolism. We are continuing to investigate multi-enzyme systems, such as 2-oxoacid dehydrogenase, building on our structure determination of a subassembly and identification of a new mechanism of intersubunit-communication. Transport. We are investigating the movement of drugs and proteins across biological membranes. We will continue studies of a variety of energy-driven transporters, their assembly and mechanism, based upon our crystal structures.

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Grant Details

Amount Awarded 342635
Applicant Surname Luisi
Approval Committee Basic Science Interview Committee
Award Date 2010-04-19T00:00:00+00:00
Financial Year 2009/10
Grant Programme: Title Senior Research Fellowship Basic Renewal
Internal ID 076846/Z/05/B
Lead Applicant Prof Ben Luisi
Partnership Value 342635
Planned Dates: End Date 2011-09-30T00:00:00+00:00
Planned Dates: Start Date 2010-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Sir Tom Blundell