With the same participants

C2D2 research 1a - Elucidation of the structure of a YD-repeat containing virulence protein from the chronic pathogen Pseudomonas aeruginosa.

Project: Other projectOther internal award

Project participant(s)

Department / unit(s)

Layman's description

This project aims to contribute to our understanding of why certain bacteria, particular ones that cause chronic infections in patients with the genetic disease cystic fibrosis, can persist for so long. It follows on some research conducted on a family of proteins that appear to be involved in allowing bacteria to stick to
other cells or even kill other cells using a toxin presented at the tip of the protein –
a toxin on a stick. Computational and experimental methods will be used to try and determine what the repeating elements that are believed to make up this 'stick' look like and to learn more about what their function is.

Key findings

FINDINGS/RESULTS

The work in the project was successful in that we achieved our aims of characterising the structures of selected YD-repeat regions of bacterial proteins. However, the conclusion is that they are unstructured, and although this is an important discovery, to prove that this is not an artefact requires further work on larger YD-protein repeats. Hence, we postponed submission of a BBSRC grant for October 2012 while we plan a strategy to collect this additional important data. As part of this work we have made significant progress in the analysis of Rhs proteins in bacteria (which contain YD-repeats) and are in a position now to write a paper on this computationally-based analysis.

COLLABORATIONS

This was a collaboration between the Thomas and Potts labs in York, which built on our previous work together. As a direct result of this funding our labs have started a new collaboration on mechanisms of biofilm formation by staphylococci. Our initial work has led to a new model of PNAG synthesis and we have submitted a manuscript describing this new model. A grant application based on this finding is being prepared for the British Heart Foundation.

STAFF

We employed a PDRA on this project for 6 months. The PDRA has now left York to train as a clinical scientist.

COMMERCIALISATION/TRANSLATION

APPLICATIONS SUBMITTED

We have clear ideas about how to take this work forward. As mentioned above our finding is likely important but needs additional support for publication and use in a grant application. The work has strengthened the relations between the Thomas and Potts group and we have benefited from sharing of tools for protein expression and purification that were being used independently on the floor previously. To expand the biological aspect we took on a Stage 3 biochemist to work on this for their project to demonstrate that E. coli could kill other related strains that lack the homologous Rhs genes. However, this student was very poor, and left the course in the Spring term having done no work on the project. Our main US competitors have now published some biological work supporting the function of Rhs proteins intra-species killing and so we can perhaps thing again about this at the structural level alone, which we have a clear lead.

As a result of the collaboration we are now working on biofilm formation by staphylococci and we are preparing a grant application for submission to the British Heart Foundation.

NMR spectroscopy will be used in this and other biofilm related work in the Potts lab. A successful preliminary application "Combatting Infectious Disease" has been submitted for a Wellcome Trust Multi-User Equipment grant to fund a new NMR spectrometer with cryoprobe.

ARTICLES SUBMITTED

None at present on the Rhs work. Article on bioinformatics of Rhs in Salmonella ready to be written.
As a result of a new collaboration between our labs (which led from this funding) we have submitted a paper describing a new model of PNAG synthesis in staphylococci during biofilm formation.
StatusFinished
Effective start/end date1/03/1230/09/12

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