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  Single-cell measurements of mutation dynamics across bacterial genome


   Faculty of Biology, Medicine and Health

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  Dr Rok Krasovec, Dr Mato Lagator, Prof Mike White  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Genetic mutations are the raw material of evolution, driving evolutionary innovations. Mutation rate is thus a key factor determining how organisms adapt to new environments and whether they survive a severe environmental challenge, such as the antibiotic treatment. It is well understood that mutation rates can vary between organisms and between environments. What is less clear is how mutations rates vary within a single organism, from one location in a genome to another. In bacteria, if mutation rates vary substantially across the genome, as has been previously suggested [1], some genes would evolve resistance faster than others.

Project will focus on the understanding of ‘local’ mutation rates and how potentially heterogenic mutation rates in different genomic regions might affect evolution of antimicrobial resistance. The project will bring together state-of-the-art assays for estimating mutation rates in bacterial populations [2] and single cells, and synthetic biology tools [3].

Our inter-disciplinary approach will allow us to to carry out a detailed analysis of ‘local’ mutation rates. Having a detailed spatial map of mutation rates within a cell will identify regions with high or low mutation rates, which will help us to understand how rapidly resistance evolution occurs in different genomic regions.

Identifying genomic regions with lower mutation rates and thus lower rates of antimicrobial resistance will give us a fundamental insight into the mechanics of how evolution works and will provide a novel research direction in the design and development of drugs.

Biological Sciences (4)

References

[1] Dillon, M. M., Sung, W., Lynch, M. & Cooper, V. S. Periodic Variation of Mutation Rates in Bacterial Genomes Associated with Replication Timing. mBio 9, e01371-01318, (2018). doi:10.1128/mBio.01371-18
[2] Krašovec, R., Richards, H., Gifford, D.K., Hatcher, C., Faulkner, K.J., Belavkin, R.V., Channon, A., Aston, E., McBain, A.J. and Knight, C.G. (2017) Spontaneous Mutation Rate Is a Plastic Trait Associated with Population Density across Domains of Life. PLOS Biology, 15, e2002731. doi: 10.1371/journal.pbio.2002731
[3] Lagator, M., Sarikas, S., Acar, H., Bollback, J. P. & Guet, C. C. Regulatory network structure determines patterns of intermolecular epistasis. eLife 6, e28921, (2017). doi:10.7554/eLife.28921
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 About the Project