Dissecting the molecular mechanisms of antibiotic resistance in bacterial pathogens


   Faculty of Biological Sciences


About the Project

Antibiotics make possible the treatment and cure of life-threatening bacterial infections. Since their introduction in the middle years of the 20th Century, they have added ~10 years to the human lifespan, and have become a cornerstone of modern medicine. Unfortunately, the utility of these agents is being rapidly eroded as pathogenic bacteria evolve to resist their effects. Compounding the issue, in the last 50 years only two truly novel antibiotic classes have been developed for treating serious bacterial infection. If this problem is not addressed as a matter of urgency, 300 million people worldwide are expected to die prematurely between now and 2050, and antimicrobial resistance (AMR) will overtake cancer as a cause of death. 

The O’Neill laboratory at Leeds is actively pursuing several complementary approaches to better understand and address this phenomenon, and has a specific focus on understanding the mechanisms that allow ’superbugs’ to resist the effects of antibiotics. Study of these mechanisms not only provides important fundamental insights into the biology of AMR, but also offers valuable strategic intelligence to inform the discovery of new generations of antibiotics capable of overcoming or circumventing existing resistance mechanisms. We are currently looking for a talented and motivated PhD candidate to help us elucidate the molecular detail of antibiotic resistance mechanisms found in major human pathogens such as Staphylococcus aureus.

Please see the O’Neill lab website for more information about what we do, and links to our published work:

https://biologicalsciences.leeds.ac.uk/molecular-and-cellular-biology/staff/119/professor-alex-o-neill

Eligibility: 

You should hold a first degree equivalent to at least a UK upper-second class honours degree or a MSc degree in a relevant subject. This project would suit someone with a strong background in tissue engineering, cancer biology or closely-related areas. Additional experience of conducting research in a multidisciplinary setting is highly desirable. Upon completion of the PhD, the successful candidate will be uniquely equipped for high-demand careers within academia or industry with desirable skills in bioengineering, regenerative medicine and cancer/cell biology.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Biological Sciences minimum requirements in IELTS and TOEFL tests are:

  • British Council IELTS - score of 6.0 overall, with no element less than 5.5
  • TOEFL iBT - overall score of 87 with the listening and reading element no less than 20, writing element no less than 21 and the speaking element no less than 22.

How to apply:

To apply for this project applicants should complete an online application form and attach the following documentation to support their application. 

  • a full academic CV
  • degree certificate and transcripts of marks
  • Evidence that you meet the University's minimum English language requirements (if applicable).
  • Evidence of funding

To help us identify that you are applying for this project please ensure you provide the following information on your application form;

  • Select PhD in Biological Sciences as your programme of study
  • Give the full project title and name the supervisors listed in this advert

Funding Notes


References

Mohamad M, Nicholson D, Saha CK, Hauryliuk V, Edwards TA, Atkinson GC, Ranson NA, O’Neill AJ (2022). Sal-type ABC-F proteins: intrinsic and common mediators of pleuromutilin resistance by target protection in staphylococci. Nucleic Acids Research, 50: 2128-2142
Crowe-McAuliffe C, Murina V, Turnbull KJ, Kasari M, Mohamad M, Polte C, Takada H, Vaitkevicius K, Johansson J, Ignatova Z, Atkinson GC, O’Neill AJ, Hauryliuk V, Wilson DN (2021). Structural basis of ABCF-mediated resistance to pleuromutilin, lincosamide, and streptogramin A antibiotics in Gram-positive pathogens. Nature Communications, 12: 3577
Wilson DN, Hauryliuk V, Atkinson GC, O'Neill AJ (2020). Target protection as a key antibiotic resistance mechanism. Nature Reviews Microbiology, 18: 637-648
Kime L, Randall CP, Banda FI, Coll F, Wright J, Richardson J, Empel J, Parkhill J, O'Neill AJ. 2019. Transient Silencing of Antibiotic Resistance by Mutation Represents a Significant Potential Source of Unanticipated Therapeutic Failure. mBio, 10: e01755-19

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