Unveiling post-transcriptional regulation by sRNAs in C. jejuni

Lead Research Organisation: University of Warwick
Department Name: Warwick Medical School

Abstract

Programme overview:
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address important applied biomedical research questions in priority areas aligned with industry. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.

Project:
An unexpected and exciting finding of the post-genomic era has been the emerging idea that non-coding RNAs play an important role in all domains of life, including in bacteria. Like many other non-coding RNAs, small regulatory RNAs (sRNA) in bacteria interact with other RNAs and proteins in order to regulate bacterial lifestyle. During the past decade, sRNA studies revealed that sRNA-mediated regulation of gene expression is critical for controlling growth, antibiotic resistance and virulence of pathogenic bacteria.

Campylobacter jejuni (C. jejuni) is known to be the most common cause of bacterial gastroenteritis in developed countries. However, C. jejuni is one of the least understood enteropathogens. Through the application of microbial pathogenomics and bioinformatics this we aim to elucidate the mechanisms through which sRNAs regulate C. jejuni's metabolic network and virulence. The project will combine the use of both experimental biology techniques and computational and statistical modeling of high-throughput -omics data. The data of sRNA and mRNA expression and both the in silico predicted and experimentally determined RNA-RNA interactome of C. jejuni will be analysed in order to develop global regulatory networks.

The models built from these digital technologies and informatics approaches will give us an unparalleled understanding of C. jejuni virulence and environmental persistence mechanisms. They will aid the discovery of regulatory networks that can be targeted for killing pathogenic C. jejuni in humans or breaking the transmission chain by eradication in chicken flocks and persistence in supermarket chicken or counteracting the emergence of antibiotic resistance or even exploit them for fighting and manipulating other pathogenic organisms. We aim to identify and test such sRNA networks, thus providing tools for future synthetic biology translational approaches that can be used to design targeted and advanced therapeutics and diagnostics.

Publications

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