DiMeN Doctoral Training Partnership: First look: Whole genome sequence analysis of Shigella from South Africa

Bacteria of the genus Shigella are the leading bacterial cause of diarrhoeal illness in children in low-and-middle income nations, but there is no licensed vaccine and they are increasingly antimicrobial resistant (AMR). Understanding this disease and its AMR in endemic areas is of global concern as shigellosis also occurs in high-income nations, frequently contracted through travel and onward transmission. In addition to the direct morbidity and mortality of shigellosis cases, childhood diarrhoeal illness is linked with life-long sequelae including stunted growth and impaired cognitive development. Whole Genome Sequence Analysis (WGSA) of Shigella is currently transforming our understanding of the epidemiology, AMR and biology of shigellosis, but this approach has yet to be applied in many of the regions where the disease is most common, resulting in critical knowledge and surveillance gaps. One such under-sampled endemic region is Africa.
In this computational biology project, you will work with whole genome sequence data from over 500 isolates of the two most prevalent Shigella types recently collected in South Africa. South Africa is a demographically-diverse nation that is particularly relevant to the study of global infectious diseases spread through travel as it acts as an African and international transport hub. You will gain expertise in bioinformatics analysis of large molecular datasets including phylogenetic and gene-content analyses and bacterial genome wide association studies. You will then use epidemiological approaches to integrate your microbial genomic analyses with patient metadata including time, demographic characteristics, location and clinical presentation.

By doing so, you will achieve the following objectives:
1. Determine what WGSA subtypes of Shigella are most responsible for disease. This contributes to public health surveillance on a global scale, particularly for countries that have transitioned to WGSA for public health microbiology.

2. Examine AMR in the Shigella isolates including what genetic factors underpin the AMR, whether they correlate with laboratory phenotype information and if these patterns change over time. Crucial for evaluating treatment recommendations and assessing the utility of WGSA for AMR diagnostics.

3. Determine whether there are bacterial genetic markers associated with invasive shigellosis, which may identify unknown mechanisms of pathogenesis and novel therapeutic targets.

In addition to gaining scientific expertise and highly sought after computational skills, you will have access to postgraduate transferable skills training programs at two Russell group Universities and gain experience disseminating scientific findings through attending and presenting results at scientific conferences and publishing in peer reviewed journals.

The project is led by Dr Kate Baker at the Institute for Integrative Biology, University of Liverpool, where you will work closely with the Centre for Genomics Research (a world class genomics facility with a core bioinformatics staff), and your second University of Liverpool supervisor will be Professor Miren Gomora at the Institute of Infection and Global Health. Due to the interdisciplinary nature of this project, you will also be supervised by microbial genomics expert, Dr Roy Chaudhuri at the University of Sheffield, and key collaborator Dr Karen Keddy, who is head of the Enteric Diseases Reference Unit of the National Institute for Communicable Diseases, South Africa.