Taming the Viral Wolf: Cracking the Code of Gene Transfer Agents in Bacteria

Bacteria commonly exchange genetic information (DNA) in a process called horizontal gene transfer as they evolve and adapt to changes in their local environment. Understanding horizontal gene transfer and how new genetic information is incorporated and domesticated into the existing signalling network and physiology of the host is a fundamental problem in biology. Horizontal gene transfer also contributes to the spread of antimicrobial resistance, which is a leading cause of mortality worldwide. The widespread but so far neglected Gene Transfer Agents (GTAs) are peculiar virus-like particles that were domesticated from ancestral bacterial viruses to now serve as nanomachines for the host bacteria. GTAs facilitate the exchange of genetic information by packaging and disseminating the DNA of the host bacteria. GTAs have a unique but poorly characterized lifecycle yet present an excellent opportunity to study the fascinating biology and fundamentals of domestication of genetic information, and to engineer GTA for biotechnological or therapeutic purposes.

Several key advances from the community and my group now make it timely to investigate and exploit GTA biology. Building on these key advances, the student will aim to develop a better understanding of fundamental GTA biology and to characterize the process of domestication of genetic information to inform the development and engineering of synthetic GTA particles.

The project comes with a multidisciplinary training, including molecular microbiology, fluorescence microscopy, ChIP-seq, RNA-seq, protein-protein interaction studies and structural biology. This will provide you highly transferrable skills and a wide choice of career options.

You will be based in the laboratory of Prof. Tung Le (www.tunglelab.org) in the Department of Molecular Microbiology at the John Innes Centre, a world-class institute for plant and microbial research.

Applications are welcomed from students across the biological sciences who have a desire to work on a multidisciplinary project. Informal enquiries to tung.le@jic.ac.uk are welcome.

References

Tran NT, Tung Le. (2023) Control of a gene transfer agent cluster in Caulobacter crescentus by transcriptional activation and anti-termination. Nature Communications, 15, 4749 (2024). https://doi.org/10.1038/s41467-024-49114-2

Banks EJ, Tung Le. (2024) Co-opting bacterial viruses for DNA exchange: structure and regulation of gene transfer agents. Current Opinion in Microbiology 2024, 78:10243. https://doi.org/10.1016/j.mib.2024.102431

Gozzi KR, Tran NT, Modell JW, Tung Le, Laub MT. (2022). Prophage-like gene transfer agents promote Caulobacter crescentus survival and DNA repair during stationary phase. PLOS Biology 2022, 20:e3001790.

Soucy, S. M., Huang, J. & Gogarten, J. P. Horizontal gene transfer: building the web of life. Nat Rev Genet 16, 472–482 (2015).

Arnold, B. J., Huang, I.-T. & Hanage, W. P. Horizontal gene transfer and adaptive evolution in bacteria. Nat Rev Microbiol 20, 206–218 (2022).