Associate Professor Sharon Kendall, Professor Brendan Wren, Professor Dirk Werling & Dr Dong Xia 

Tuberculosis (TB), caused by a unique group of bacteria called mycobacteria, is a devastating disease in both human and animal populations. The identification of virulence factors and their roles in host-pathogen interactions in mycobacteria have largely been performed in a lab-adapted reference strains. Over the last decade, the accumulation of whole genome sequence data from field strains has revealed an unexpected genetic diversity within mycobacteria. The genetic variation within circulating lineages and bias of studies that use the reference strains means that we currently have a blinkered view of host:pathogen interactions in the context of TB. The aim of this project is to better understand how genetic variation observed in circulating strains influences host-pathogen interactions in bovine TB. We have isolated and genome sequenced field strains of Mycobacterium bovis circulating in North Africa (unpublished). These strains will be used in this project to better understand how genetic variation influences host-pathogen interactions in bTB.  

During the project you will gain experience in bioinformatic analysis of whole genome sequences, molecular microbiology- including the generation transposon libraries, and measuring the immune response in a natural host. You will be supervised by a team of committed and experienced supervisors with complementary skill-sets. You will benefit by interacting with scientists working in both human and animal health contexts and learn to translate findings between human and animal populations using a One Health approach.  

Objectives:  

• To measure the impact of strain diversity on the response of host innate immune cells. 
• To measure the impact of strain diversity on the pathogen fitness in response to immune pressure 
• To measure the impact of strain diversity on epitope variation through comparative genomics 
• To measure the contribution of genes to pathogen fitness in the field strains using Transposon Insertion sequencing (TnSEQ). 

Closing date for applications: Sunday March 10th at 5:00 pm

Further details about the project may be obtained from: skendall@rvc.ac.uk

Further information about PhDs at RVC and how to apply:

https://www.rvc.ac.uk/study/postgraduate/phd

https://www.rvc.ac.uk/study/postgraduate/phd#tab-available-studentships

Key References:

Tientcheu, L.D., Koch, A., Ndengane, M., Andoseh, G., Kampmann, B. and Wilkinson, R.J. (2017), Immunological consequences of strain variation within the Mycobacterium tuberculosis complex. Eur. J. Immunol., 47: 432-445. https://doi.org/10.1002/eji.201646562.  

Orgeur M, Brosch R. Evolution of virulence in the Mycobacterium tuberculosis complex. Curr Opin Microbiol. 2018 Feb;41:68-75. doi: 10.1016/j.mib.2017.11.021. Epub 2017 Dec 5. PMID: 29216510. 

Zwyer M, Çavusoglu C, Ghielmetti G et al. A new nomenclature for the livestock-associated Mycobacterium tuberculosis complex based on phylogenomics [version 2; peer review: 2 approved]. Open Res Europe 2021, 1:100 (https://doi.org/10.12688/openreseurope.14029.2)  

Gibson AJ, Stiens J, Passmore IJ, Faulkner V, Miculob J, Willcocks S, Coad M, Berg S, Werling D, Wren BW, Nobeli I, Villarreal-Ramos B, Kendall SL. Defining the Genes Required for Survival of Mycobacterium bovis in the Bovine Host Offers Novel Insights into the Genetic Basis of Survival of Pathogenic Mycobacteria. mBio. 2022 Aug 30;13(4):e0067222. doi: 10.1128/mbio.00672-22.