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Assembly of the DNA competence uptake pathway in Gram negative bacteria


Project Description

Bacteria can take up DNA by three main mechanisms, transduction, conjugation and natural transformation, the latter being frequently termed ‘natural competence’. These mechanisms of horizontal gene transfer are major contributors to bacterial genetic diversity, a process which has widespread ramifications for the spread of antibiotic resistance and the propagation of virulence in animal and human pathogens. This project is focussed on the process of natural competence- the property of some bacteria to take up DNA from the external environment, generally triggered by a specific stimulus (eg nutritional privation). Natural transformation was discovered through the classic experiments of Frederick Griffith in the 1920s, demonstrating that avirulent pneumococci could be transformed into a virulent state through addition of heat-killed virulent bacteria. The ‘transforming factor’ was later shown to be DNA but, even some 90 years later, relatively little is understood about the molecular basis for DNA uptake. At the heart of this project lies a fundamental biological question: how do some bacteria take up a long, hydrophilic polymer such as DNA across two membranes and into the cell? The proteins responsible for natural competence have been identified, but an understanding of how they work in concert is lacking. This project will use a combination of biochemical methods to reconstruct the DNA uptake ‘machine’ in vitro, and use the assembly to answer fundamental questions about how this important process occurs at the molecular level.

Funding Notes

This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

Informal enquiries may be made directly to the primary supervisor.

References

V Karuppiah, RF Collins, A Thistlethwaite, Y Gao, JP Derrick. (2013). Structure and assembly of an inner membrane platform for initiation of type IV pilus biogenesis. Proceedings of the National Academy of Sciences of the United States of America, n/a(n/a), n/a. eScholarID:212364

DOI:10.1073/pnas.1312313110

Collins, R. F., Hassan, D., Karuppiah, V., Thistlethwaite, A. and Derrick, J. P. (2013) Structure and mechanism of the PilF DNA transformation ATPase from Thermus thermophilus. Biochemical Journal. 450, 417-425

Berry, J.-L., Phelan, M. M., Collins, R. F., Adomavicius, T., Tonjum, T., Frye, S. A., Bird, L., Owens, R., Ford, R. C., Lian, L.-Y. and Derrick, J. P. (2012) Structure and Assembly of a Trans-Periplasmic Channel for Type IV Pili in Neisseria meningitidis. Plos Pathogens. 8 DOI e1002923

Karuppiah, V., Berry, J.-L. and Derrick, J. P. (2011) Outer membrane translocons: structural insights into channel formation. Trends in Microbiology. 19, 40-48

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