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Loving the poison: molecular basis for metabolism of the widely-used food preservative, propionate in Pseudomonas aeruginosa.

Lead Research Organisation: University of Cambridge
Department Name: Biochemistry

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
 
Description We have identified (through FBDD approaches, with back-to-back XChem grants) inhibitors for the PrpC and PrpB proteins. This is significant because inhibition of PrpC/PrpB causes lethality in the presence of propionate, which is abundant in infection scenarios. This is therefore a route towards antibacterial development, and we are working with this in mind.
Exploitation Route We are in discussion with LifeArc about the best way to move this forward. We also received BBSRC IAA funding to do the same.
Sectors Pharmaceuticals and Medical Biotechnology
 
Description LB19242 2-METHYLISOCITRATE LYASE AS A NOVEL ANTIBACTERIAL AGENT.
Amount £35,000 (GBP)
Organisation Diamond Light Source 
Sector Private
Country United Kingdom
Start 09/2017 
End 09/2019
 
Description LB21553 TARGETING METHYLISOCITRATE LYASE (PRPB) IN THE HUMAN PATHOGEN, PSEUDOMONAS AERUGINOSA.
Amount £35,000 (GBP)
Organisation Diamond Light Source 
Sector Private
Country United Kingdom
Start 08/2019 
End 10/2020
 
Title Fragment based drug design 
Description FBDD carried out in collaboration with XChem on PrpB and PrpC 
Type Of Material Biological samples 
Year Produced 2019 
Provided To Others? No  
Impact N/A at present 
 
Title in silico systems approaches to transcriptional networks 
Description My PDRA visited Brazil (Silva-Rocha lab) to learn how to carry out network analyses of his transcriptome data 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2017 
Provided To Others? No  
Impact 1 paper published, 1 paper invited from publisher, 1-2 papers in preparation (to be published 2018 sometime) 
 
Title PRIDE proteomic dataset 
Description proteomic data prpC mutant vs WT accession PXD015792 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
Impact N/A 
 
Title RNAseq dataset 
Description RNAseq dataset prpC mutant vs WT accession E-MTAB-10077 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
Impact N/A 
 
Description Collaboration with University of Sao Paolo 
Organisation Universidade de São Paulo
Country Brazil 
Sector Academic/University 
PI Contribution We hosted a student (Greicy Pereira) from USP for 7 months.
Collaborator Contribution Greicy contributed towards a publication, and a good portion of her PhD dissertation work was done in my laboratory.
Impact See published papers arising from this grant
Start Year 2021
 
Description Strengthening of collaborations 
Organisation University of Cambridge
Department Cambridge Centre for Proteomics
Country United Kingdom 
Sector Academic/University 
PI Contribution Continuation (from 12-05-2008 to the present day) and strengthening of my ongoing collaborative partnership with Dr David Spring in the Chemistry Dept and Dr Kathryn Lilley (co-applicant) in the Cambridge Centre for Proteomics research. Both ongoing collaborations continue to be active and productive.
Start Year 2008