Type IV secretion systems (T4SS) are ubiquitous nanomachines that assemble at the bacterial inner and outer membranes to orchestrate the delivery of proteins and DNA into bacterial and eukaryotic cell targets. T4SSs are not only the crucial drivers of antibiotic resistance spreading during bacterial conjugation, they are also capable of secreting toxins that are lethal to other bacteria and human cells. T4SSs can be exploited as drug targets against antibiotic resistance spreading and bacterial infectious diseases.
This exciting PhD project aims to unveil the structural and functional details underlying the mechanism of DNA and toxins secretion by T4SSs. The project will use single particle cryo-electron microscopy to obtain near-atomic details that elucidate how substrates are recruited, transported and secreted to target cells. This is a multidisciplinary project that involves the biochemical isolation and characterization of large membrane complexes combined with cutting-edge single particle cryo-EM.
How to apply
Please send your CV (including contact details of two referees) with a cover letter describing why you are suitable for this PhD studentship and interested in the project to Dr Tiago Costa [email protected]
The project will start on October 2020 or anytime after May 2020 depending on candidate availability.
About the candidate
Applicants should have a strong background in protein biochemistry. Some preliminary experience with cryo-electron microscopy is desirable but not essential.
Candidates must have or expected to gain a First class or Upper Second class Honours degree in Biological Sciences (or other related appropriate science subject). Preference will be given to candidates with a Master’s degree or equivalent research experience in a relevant subject area.
Due to funding availability, only Home/EU students can be considered for this studentship.
Key words: cryo-electron microscopy, type IV secretion system, macromolecular complex, protein- DNA injection, antibiotic resistance.
1. Williams, A.H., Redzej, A., Rolhion, N., Costa, T.R.D., Rifflet, A., Waksman, G., and Cossart, P. (2019). The cryo-electron microscopy supramolecular structure of the bacterial stressosome unveils its mechanism of activation. Nature communications 10, 3005.
2. Sgro, G.G., Costa, T.R.D., Cenens, W., Souza, D.P., Cassago, A., Coutinho de Oliveira, L., Salinas, R.K., Portugal, R.V., Farah, C.S., and Waksman, G. (2018). Cryo-EM structure of the bacteria-killing type IV secretion system core complex from Xanthomonas citri. Nat Microbiol 3, 1429-1440.
3. Galan, J.E., and Waksman, G. (2018). Protein-Injection Machines in Bacteria. Cell 172, 1306-1318.
4. Costa, T.R., Ilangovan, A., Ukleja, M., Redzej, A., Santini, J.M., Smith, T.K., Egelman, E.H., and Waksman,
G. (2016). Structure of the Bacterial Sex F Pilus Reveals an Assembly of a Stoichiometric Protein- Phospholipid Complex. Cell 166, 1436-1444 e1410.
5. Costa, T.R., Felisberto-Rodrigues, C., Meir, A., Prevost, M.S., Redzej, A., Trokter, M., and Waksman, G. (2015). Secretion systems in Gram-negative bacteria: structural and mechanistic insights. Nature reviews Microbiology 13, 343-359.