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Understanding how pandemic microbes evolve

Principal Supervisor: Professor David Grainger, School of Biosciences

Co-supervisor: Manuel Banzhaf

PhD project title: Understanding how pandemic microbes evolve

University of Registration: University of Birmingham

Project outline:

Understanding the rules of species evolution is a fundamental question in biology. The emergence, spread and demise of harmful organisms, which can cause pandemics, is particularly important. You will focus on the bacterial species Vibrio cholerae. Recent advances in phylogenetics, model systems, and molecular tools, provide a timely opportunity to substantially progress our understanding. Your goal is to determine how evolution drives species development and pandemic potential. You will take a multi-level approach encompassing global species genetics, model ecosystems, and molecular mechanisms.

Currently, we cannot explain how the strain causing the current cholera pandemic arose, let alone predict why, where or when the next one might arise. The “success” of V. cholerae depends on its ability to adapt to different surroundings. Normally, the bacterium resides in aquatic environments and persists by forming biofilms on the chitinous surfaces of plankton and shellfish. These biofilms are rapidly disassembled on ingestion by a human or aquatic host. Following host colonisation, disease is caused by the extrusion of toxins (1). Hence, to understand what is special about the “pandemic” strain, it is essential to understand how the bacterium is able to switch between lifestyles. Recent work has generated a wealth of V. cholerae genome sequences (>10,000) from decades of outbreaks associated with the current worldwide pandemic (2,3). Our laboratory is using these data to try and understand key genetic changes that influence lifestyle choice and pandemic potential. Our work involves the application of bacterial genomics, molecular biology, and host organism colonisation models, to study lifestyle changes (4,5).

References:

  1. Nelson, EJ, Harris, JB, Morris, JG, Calderwood, SB, Camilli, A. (2009) Cholera transmission: the host, pathogen and bacteriophage dynamic. Nature Reviews Microbiology 7, 693-702.
  2. Domman D, Quilici ML, Dorman MJ, Njamkepo E, Mutreja A, Mather AE et al. (2017) Science. Integrated view of Vibrio cholerae in the Americas. 358:789-793.
  3. Weill FX, Domman D, Njamkepo E, Tarr C, Rauzier J, Fawal N et al. (2017) Genomic history of the seventh pandemic of cholera in Africa. Science. 358:785-789.
  4. Manneh-Roussel J, Haycocks JRJ, Magán A, Perez-Soto N, Voelz K, Camilli A, Krachler AM, Grainger DC. (2018) cAMP Receptor Protein Controls Vibrio cholerae Gene Expression in Response to Host Colonization. mBio. 9:e00966-18.
  5. Haycocks, JRJ, Warren, GZL, Walker, LM, Chlebek, JL, Dalia, TN, Dalia, AB, Grainger, D (2019) The quorum sensing transcription factor AphA directly regulates natural competence in Vibrio cholerae. PLoS Genet. 15:e1008362.

BBSRC Strategic Research Priority: Sustainable Agriculture and Food: Microbial Food Safety & Understanding the Rules of Life: Microbiology & Systems Biology

Techniques that will be undertaken during the project:

Protein purification, Chromatin Immunoprecipitation, Illuminia Sequencing and associated bioinformatics, PCR, Radioisotopes, Microscopy, In vitro DNA binding assays, Reporter assays, Microbial cell culture, mutagenesis.

Contact: Professor David Grainger, University of Birmingham