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Cordwell, S. J.

Publications and source records attributed to Cordwell, S. J..

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Standardization and Harmonization of Distributed Multi-National Proteotype Analysis supporting Precision Medicine Studies

Cancer has no borders: Generation and analysis of molecular data across multiple centers worldwide is necessary to gain statistically significant clinical insights for the benefit of patients. Here we conceived and standardized a proteotype data generation and analysis workflow enabling distributed data generation and evaluated the quantitative data generated across laboratories of the international Cancer Moonshot consortium. Using harmonized mass spectrometry (MS) instrument platforms and standardized data acquisition procedures, we demonstrated robust, sensitive, and reproducible data generation across eleven sites in nine countries on seven consecutive days in a 24/7 operation mode. The data presented from the high-resolution MS1-based quantitative data-independent acquisition (HRMS1-DIA) workflow shows that coordinated proteotype data acquisition is feasible from clinical specimens using such standardized strategies. This work paves the way for the distributed multi-omic digitization of large clinical specimen cohorts across multiple sites as a prerequisite for turning molecular precision medicine into reality.

molecular biology

Assigning a role for chemosensory signal transduction in Campylobacter jejuni biofilms using a combined omics approach

Biofilms serve as a protective mechanism for bacteria to cope with environmental stress. Whilst ordinarily a fastidious organism, it has been long suggested that C. jejuni is able to utilise this mode of growth as a way to transmit infection from the avian host to humans. Herein, we undertook a combinatorial approach to examine differential expression of C. jejuni genes and protein abundance during biofilm formation. RNA sequencing and proteomics via quantitative liquid chromatography - tandem mass spectrometry (LC-MS/MS) revealed biofilm growth induced a substantial rearrangement of the C. jejuni transcriptome and proteome, with [~]600 genes differentially expressed in biofilms compared to planktonic cells. Biofilm-induced genes / proteins were those involved in iron metabolism and acquisition, cell division, glycan production and attachment, while those repressed were associated with metabolism, amino acid uptake and utilisation, and large tracts of the chemotaxis pathway. We further examined the role of chemotaxis in C. jejuni biofilm formation by assessing the behaviour of isogenic strains with deletions of the cheV and cheW genes. Both {Delta}cheV and {Delta}cheW exhibited a significant decrease in directed motility when compared to wild-type C. jejuni. Both mutants also demonstrated an increase in autoagglutination ability and increased biofilm formation. A subtle difference was also observed between the phenotypes of {Delta}cheV and {Delta}cheW mutants, both in motility and biofilm formation. This suggests roles for the CheV and CheW signal transduction proteins and may present signal transduction as a potential method for modulating C. jejuni biofilm formation. Author summaryCampylobacter jejuni is a gastroenteric bacterium that is responsible for most cases of bacterial food poisoning in the developed world. The organism commonly resides in avian reservoirs and is passed to humans through contaminated poultry and animal products. Ordinarily, C. jejuni requires a strict set of conditions in order to survive and cause infections in humans. Biofilms are a method of bacterial growth that may provide shielding from harsh environments and provide an important link between reservoirs and human hosts. In this study, we have utilised a multi-platform approach to compare gene expression and protein abundance in planktonic C. jejuni cells and those growing as a biofilm. We subsequently focused on the chemosensory system of C. jejuni and demonstrated that signal transduction proteins play a role in biofilm formation. Our work has provided a broad profile of which genes are important to C. jejuni biofilms and that the chemosensory pathway has an influence on biofilm formation.

microbiology