Marie Curie ITN PhD project:
New approaches to overcoming the resistance problem in bacterial pathogens: exploring metagenomes for novel antibiotics
 

Supervisor: Prof E M H Wellington

Other Supervisor: Prof David Hodgson and Prof S Donadio KtedoGen srl

Application deadline 31 May 2012

Project overview

Background: Antibiotic resistance amongst bacterial pathogens is a well-established problem and some pathogens are fast becoming untreatable due to excessive use and misuse of antibiotics. An additional problem is the diminishing range of antibiotics used for veterinary purposes which will not result in cross resistance to clinically important drugs. Overcoming this problem requires a new look at the way in which bacterial infections are controlled and how we can discover new drugs with modes of action that are more resilient to bacterial resistance mechanisms. One approach is to put more focus on natural product discovery from bacteria that have not been screened before and clone pathways which could subsequently be used to manipulate improved resilience to resistance.

The aim of this research is to exploit the uncultured fraction of microorganisms in diverse habitats, this is possible as in most environments such as soil this fraction represents over 90% of the total bacterial population. The advent of deep sequencing to explore metabolite diversity coupled with new techniques developed in synthetic biology have advanced the potential to recover pathways and synthesize the metabolites from non-

culturable bacteria.

Summary plan: We will use novel approaches to obtain large fragments of DNA from habitats where unique bacterial diversity has been detected either by functional or phylogenetic analysis of total community DNA. The DNA will be cloned as a metagenome into a range of vectors for subsequent analysis. A variety of methods will be used to generate libraries and captured pathways will be detected by a combination of screening for targeted pathway genes, mobilization methods, and expression screening using suitable hosts. Any hits will be sequenced and used for further analysis for expression and chemical characterisation. The studentship is part of an EU training network and will involve close collaboration with biotech and pharmaceutical companies KtedoGen srl and Pfizer.

Special features: The project is part of an international training network so further training will be provided on all aspects of drug discovery and combating infections. The two companies involved will have fellowships and be fully integrated in the programme. A substantial stipend is available for a talented and ambitious candidate who wants to make a career in science and is interested in the area of drug discovery and the antibiotic resistance problem.

Funding

• Exact salary (including mobility allowance) will be confirmed upon appointment but will be at least £39,000.

Eligibility Criteria

Applicants must meet the requirements of the EU Marie Curie training schemes.

• Mobility

The researcher must not have resided, worked or studied in the United Kingdom for more than 12 months in the 3 years prior to the time of recruitment. Short stays are not taken into account.

• Qualification and Research Experience
  

Early stage researchers have at the time of recruitment not yet been awarded the doctorate degree and are in the first 4 years (full-time equivalent) of their research careers.

• English language

It is a requirement that overseas students will show that their ability to understand and express themselves in both written and spoken English is sufficiently high for them to derive the full benefit from the PhD. Please note that the requirement for admission is IELTS 6.5 (with no component below 6.0) or equivalent TOEFL score. More information can be found at: http://www2.warwick.ac.uk/services/international/apply/englishlanguage/.

Contact details for application enquiries:

Professor Elizabeth Wellington email: E.M.H.Wellington@warwick.ac.uk