Towards new antibacterial drugs to treat infections caused by multidrug-resistant bacteria: identification and characterization of novel natural product antibiotics

Antibiotics make possible the treatment and cure of life-threatening bacterial infections and have added over a decade to the average human lifespan. Unfortunately, the utility of these drugs is being rapidly eroded as pathogenic bacteria evolve to resist their effects; in 2019, antimicrobial resistance (AMR) killed ~1.3 million people worldwide, and this figure is set to rise to 10 million by 2050. To address this problem, it is imperative that new antibiotics are discovered as matter of urgency. 

The best-validated source of antibiotics is nature, with most of our existing antibiotic armamentarium deriving from soil microorganisms. However, this source stopped routinely yielding novel compounds decades ago and was largely abandoned in the search for new antibiotics. Viewed through the lens of our current knowledge, this was not because this source had been comprehensively mined – far from it, in fact– but simply that continuing to screen the same types of microorganisms in the same way will not deliver new antibiotics (“if you do what you have always done, you get what you always got”).

Our view is that nature remains far and away the best place to look for new antibiotics, though strategic innovation will be essential to do so effectively. The O’Neill lab is working to systematically address the pit-falls and bottle-necks in natural product antibiotic discovery, identifying new sources/ types of microorganism for testing, creating novel screening tools for improved detection of antibiotics, and evolving approaches that allow rapid assessment of the chemical/ functional novelty and therapeutic potential of these compounds .

The proposed studentship will not only work to establish innovative approaches to antibiotic discovery, but will also deploy these to identify new drug candidates effective against the most problematic types of multi-drug resistant bacteria. Building on exciting recent findings in our lab, this project will utilise ichip technology to recover microorganisms new to science from a variety of sources, and will screen these for antibiotic production using novel tools/ approaches that will be created or evolved over the course of the study. Collectively, this project will rejuvenate and accelerate the discovery of new antibiotics from nature, thereby helping to address the global challenge of AMR and providing the appointed student with cutting-edge, multidisciplinary training in bacteriology, molecular biology and antibiotic discovery.

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 background in molecular microbiology, biochemistry, drug discovery 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 drug discovery.

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