ProfessorStuart Cordwell

Project Opportunities

Title: Identification of proteins specific to transmissible Pseudomonas aeruginosa in cystic fibrosis infection

Summary of opportunity:

This project will characterize the molecular basis for increased infectivity caused by an epidemic strain of Pseudomonas aeruginosa (AES-1) which infects many patients treated in cystic fibrosis (CF) clinics in eastern Australia.

Opportunity synopsis:

It is likely that unique genetic sequences within P. aeruginosa AES-1 are expressed and contribute to increased infectivity and virulence, specifically in the CF lung microenvironment and that the expression of these proteins under altered environmental and physiological conditions can be detected using proteomics when compared to less virulent and virulent, non-CF P. aeruginosa. The aims of this project are to identify P. aeruginosa AES-1-specific:

1. Proteins and pathways by comparing membrane-associated, cytoplasmic and secreted proteins from P. aeruginosa AES-1R, Manchester Epidemic (CF) Strain (MA), PA14 and PAO1 grown in nutrient rich and minimal media, medium mimicking the lung in CF and biofilms;
2. Infectivity and virulence determinants by examining P. aeruginosa AES-1R, MA, PAO1 and PA14 protein and virulence profiles during adaptation to nutrient rich medium.

Investigations will be carried out using complementary proteomics and phenotypic assays that will provide both data acquisition and validation. Identification of P. aeruginosa AES-1R-specific proteins will aid in determining novel protein targets suitable for therapeutic intervention and infection control.

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Project Opportunities

Title: Post-translational modifications in bacterial proteins

Summary of opportunity:

This project will identify novel proteins that are post-translationally modified in bacterial pathogens and the role of such modification in virulence.

Opportunity synopsis:

Post-translational modifications, such as phosphorylation and glycosylation, modify the structure and function of proteins. Furthermore, protein cleavage provides antigenic variation and may dictate novel functions. This project will examine both global protein modifications (e.g. phosphoproteomics) as well as characterize modifications in individual proteins such as the CadF adhesin of Campylobacter jejuni. Oxidative stress, caused by the release of toxic reactive oxygen species (ROS) from inflammatory immune cells, must be overcome by the majority of human pathogens. This project aims to identify how oxidative stress modifies protein expression, as well as determine whether disulfide bond formation is induced under such conditions.

----------Current Research Projects----------

Current Projects in Stuart's group include:

Defining the function of N-linked glycosylation in Camplyobacter jejuni

Exploring the protease complement of C. jejuni

Identifying new protein vaccines for Pseudomonas aeruginosa

Revealing how nutritional requirements influence host-pathogen interactions

Developing membrane protein cross-linking mass spectrometry for the interactome in bacteria

Determining the role of redox post-translational modifications in biological systems

Understanding signaling by phosphorylation and other PTMs in myocardial ischemia