Knot So Simple: Untangling Bacterial Chromosome Structure, Conformation and Gene Expression

Primary supervisor - Dr Ben Evans

Understanding the mechanisms used by bacterial pathogens to adapt to drug exposure is key to developing new approaches to combat them. Much work has focussed on the roles of mutations and mobile elements in this regard. However, these are not the only ways that bacteria can respond under stress. Bacteria can change the order of genes on their chromosome (the chromosome structure) or the three-dimensional arrangement of the chromosome (the chromosome conformation), altering gene expression patterns and allowing survival under stressful conditions.

When bacteria make large-scale changes to their chromosome structure, this is likely to have a dramatic impact on global gene expression levels, and indeed this was recently shown by members of the supervisory team to be the case (Waters et al, 2022). However, the role of structural changes in adapting to antibiotic exposure is unknown.

Bacterial chromosomes exist as highly organised three-dimensional structures maintained by a range of nucleoid-associated proteins (NAPs). Highly-expressed genes are often found at the boundaries of chromosome-interacting domains (CIDs). Members of the supervisory team have recently shown this to be the case in response to drug exposure (Ghosh et al, 2023). It is therefore likely that changes in chromosome structure will not only alter gene position relative to the origin of replication, but will also disrupt the nucleoid structure. The interaction between chromosome structure and conformation is currently unknown.

You will join the teams of Dr Ben Evans (UEA), Dr Emma Waters and Dr Gemma Langridge (Quadram Institute) and use a combination of genetic engineering, genomics, transcriptomics, Hi-C and chromosome structural modelling to determine the interaction between chromosome structure and conformation in the bacterium Acinetobacter baumannii, and how this impacts upon antibiotic resistance.

The Microbes, Microbiomes and Bioinformatics (MMB) Doctoral Training Partnership (DTP) is open to UK and International candidates with relevant undergraduate degrees for entry in October 2024 and offers the opportunity to undertake a fully-funded 4-year PhD research project supported by the UKRI Medical Research Council in microbiology and microbial bioinformatics.

Our unique and comprehensive training programme empowers students to feel comfortable running sophisticated computer analyses alongside laboratory work and emphasises problem-based learning in microbial bioinformatics, professional development and research skills. All MMB DTP students undertake a Professional Placement.

Interviews for shortlisted candidates will take place on Wednesday 15 May 2024.

The MRC DTP is committed to equality, diversity and inclusion. Students are selected without regard to age, disability, gender identity, marriage or civil partnership, pregnancy or maternity, ethnicity, religion or belief, sex or sexual orientation or social background. We value curiosity, independence of thought, plus an aptitude for research that combines laboratory work and bioinformatics.

For information on eligibility and how to apply: www.uea.ac.uk/phd/mmbdtp

Additional Funding Information

This project is awarded with a 4-year fully-funded studentship including direct payment of tuition fees to the University, stipend for living expenses (2023/4 rate: £18,622) and a Research Training Support Grant for each year of the studentship.