PhD opportunities

The BBSRC GW4 Universities Doctoral Training Program is currently advertising PhD projects. This is a slightly complicated process, but basically comes down to prospective students picking a project offered by scientists working at participating universities and institutions and applying to the program. I (Dr Michiel Vos, m.vos@exeter.ac.uk) offer one of these projects as part of a team of  GW4 colleagues (Prof Ed Feil, University of Bath, Dr Ben Temperton, University of Exeter and with collaborator Prof Adam Eyre-Walker, University of Sussex). Below the project description:

Quantifying the rate and fate of bacterial gene content evolution

Bacteria are the most abundant and diverse life forms on earth, vital to the functioning of all ecosystems and to human health and wellbeing. Bacteria rely on a highly diverse array of mechanisms to create genomic changes which, combined with usually enormous population sizes, can result in rapid evolutionary change. Most bacterial species have ‘fluid’ genomes, where a stable core genome is complemented by an accessory set of genes that can be rapidly taken up through lateral transfer and lost through deletion (1). Such Gene Content Changes (GCC) have been estimated to occur at rates similar to nucleotide substitution in the core genome and are likely to have more significant effects on fitness (2). Despite its importance to bacterial evolution, the rate of gene content turnover and the selective effects of GCC are not well-understood. Some researchers argue that most changes have only small effects on fitness (3), whereas others argue that most variation in accessory genes is adaptive (4). As the tempo and mode of bacterial evolution is fundamental to a wide range of fields, from molecular epidemiology to biotechnology, this controversy needs to be resolved. This project takes a comparative genomics approach to 1) explicitly measure the rate of GCC in a range of different bacteria and 2) develop novel tests of selection to quantify the selective effects of gene content change.

  1. Ochman H, Davalos LM. The nature and dynamics of bacterial genomes. Science. 2006; 311(5768):1730-3
  2. Vos M, Hesselman MC, te Beek TA, van Passel MW, Eyre-Walker A. Rates of Lateral Gene Transfer in Prokaryotes: High but Why? Trends in microbiology. 2015; 23(10):598-605
  3. Andreani, E. Hesse and M. Vos. Prokaryote genome fluidity is dependent on effective population size. 2017 ISME J doi:10.1038/ismej.2017.36
  4. McInerney, James O., Alan McNally, and Mary J. O’Connell. “Why prokaryotes have pangenomes.” Nature Microbiology. 2017 28; 2:17040. doi:10.1038/nmicrobiol.2017.40

I am second supervisor (along with Prof Sam Sheppard at Bath) on a project led by Prof Ben Raymond at the University of Exeter:

Clone wars in niche space: exploring the evolutionary and genetic basis for bacterial species

Understanding the forces that shape bacterial genetic variation is a fundamental problem in microbiology.  Classifying bacteria into meaningful species groups is also essential for applied microbiology and ecology. Many bacterial species have been shown to exhibit extensive variation in gene repertoires, where a set of core genes shared by all strains are supplemented with a set of accessory genes that are only present in a subset of strains.  The ability to exploit particular niches is thought to depend on the acquisition of a range of accessory genes, typically acquired via horizontal gene transfer (Vos et al. 2015).  However, genetic variation in core genes shared between different strains is often associated with ecological niche (Raymond et al 2010, Zheng et al 2017)(Figure 1), suggesting that variation in core genes may be ecologically significant.

This project will explore the extent to which core genetic variation arises from neutral genetic drift process and from positive selection in distinct habitats, a question with broad importance for understanding bacterial biology and evolution.  For instance, many isolates of economic and therapeutic importance (Bacillus thuringiensis biopesticides, Escherichia coli probiotics etc) are closely related to isolates capable of causing disease.  In both these cases, humans consume large doses of viable microbes in food or as therapeutic agents.  Understanding the potential of beneficial bacteria to cause harm or acquire harmful genes is particularly important for assessing the safety of these uses.   If core genetic variation limits virulence or niche shifts then the risk of these applications will be substantially reduced  (Raymond & Federici 2017).

Bacillus thuringiensis, in particular, has an excellent safety record and is the most widely applied microbial insecticide, facilitating environmentally friendly mosquito control and pest management.  Nevertheless, disagreements regarding its ecological niche, and it taxonomic status relative to Bacillus cereus, a causative agent of diarrhea, have threatened its continued use in the European Union.  In this project, the student will (1) carry out genome sequencing and phenotypic characterization of isolates from natural populations (2) apply experimental evolution and re-sequencing approaches to look for convergent adaptive mutations in novel niches (3) use CRISPR-Cas9 genome editing to introduce putative adaptive alleles into different genetic backgrounds.

Raymond, B., & Federici, B.A. (2017).FEMS Microbiology and Ecology.  doi: 10.1093/femsec/fix084

Zheng, J., Gao, Q., Liu, L., Liu, H., Wang, Y., Peng, D., Ruan, L., Raymond, B., & Sun., M.  (2017) mBio 8:e 00822-17. doi: 10.1128/mBio.00822-17.

Raymond, B., Wyres, K., Sheppard, S., Ellis, R.J., Wright, D.J., & Bonsall, M.B (2010). PLoS Pathogens 6(5): e1000905.

Vos, M., Hesselman, M., Te Beek, T., van Passel, M.,Eyre-Walker, A. (2015) Trends Microbiol 23.10: 598-605

If this seems of interest, please check the BBSRC SW BioSciences DTP website. The application deadline is Midnight, Monday 4th December 2017.

 

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