BBSRC iCASE PhD Studentship

Project Title: Bacteriocins as an alternative therapeutic option against antibiotic resistant bacteria

Project Summary: Antibiotic resistant bacterial infections place a significant burden on healthcare systems worldwide. As such, alternative and innovate approaches are needed to manage and treat bacterial infections. In this project, we will study the potential and mode of action of bacteriocins – antibacterial toxins produced by bacteria - as a therapeutic option against bacteria that resist or evade killing by conventional antibiotics. The specific objectives of the project will involve:

  1. To optimise the production of bacteriocins using cell-free transcription/translation and synthetic systems.
  2. To identify bacteriocins that are bacteriostatic against pathogenic Escherichia coli.
  3. To identify bacteriocins that act bactericidal against pathogenic E. coli.
  4. To study the mode of action of selected bacteriocins.
  5. To develop delivery systems for selected bacteriocins.

Application Deadline: 8th March 2019 

For information on how to apply:  https://www.imperial.ac.uk/bbsrc-doctoral-training-partnership/icase/application-process/

Informal enquiriesProf. Ramesh Wigneshweraraj (s.r.wig@imperial.ac.uk)


PhD Studentship: The mechanisms by which Streptococcal pathogens exploit immune receptors for innate immune evasion

A 3-year Department of Medicine PhD studentship is available to work in the laboratory of Dr Alex McCarthy, in the MRC Centre for Molecular Bacteriology and Infection (CMBI) at Imperial College London. The successful applicant will be joining an internationally-renowned Research Centre, within one of the world’s top research universities.

Streptococcal pathogens including Group A Streptococcus (GAS; S. pyogenes) and Group B Streptococcus (GBS; S. agalactiae), can cause a range of mild, invasive and deadly infections, including necrotising fasciitis (flesh-eating disease), meningitis and toxic shock syndrome. Streptococcal pathogens have often evolved sophisticated and specialised mechanisms to evade innate immune responses, in order to enhance their survival, replication, and ability to cause disease. This exciting PhD position, supervised by Dr Alex McCarthy & Prof Shiranee Sriskandan, will investigate mechanisms that enable streptococcal pathogens to evade innate immune responses, so that we can develop novel therapeutic strategies.

The goal of this project is to identify the molecular basis of streptococcal interactions with modulatory immune receptors, and to characterise how these host-pathogen interactions contribute to immune evasion. The combined use of genetic, biochemical, cellular and immunological techniques will provide unique insights into the mechanism that contribute to streptococcal immune evasion pathogenicity. The results will have broad implications in understanding streptococci biology, and will pave the way for rational design of novel anti-bacterial therapeutic approaches. The student will be based in the Flowers Building, CMBI at the South Kensington Campus of Imperial College London, which provides state of the art facilities and an exciting PhD student training environment. Prof Sriskandan holds a clinical position at the Hammersmith Campus with access to clinical samples and expertise.

The candidates should have a background in innate immunity and a strong interest in bacterial pathogenesis. Prior experience with bacteria pathogens is desirable but not essential.

Candidates must be expected to have a first class or upper second class Honours degree in biological sciences (or other appropriate science subject), and a Master’s degree or equivalent research experience in a relevant subject area. Only UK or EU nationals are eligible.

The 3-year studentship covers tuition fees and provides a tax-free stipend of £18,000 per annum.  

To apply, please send a copy of your CV, a cover letter describing why you are suitable for this PhD studentship to Nicola Tingley (n.tingley@imperial.ac.uk). Informal enquires can be sent to Dr. Alex McCarthy (a.mccarthy@imperial.ac.uk). 

Application Deadline: CLOSED


PhD Studentship: Molecular basis of antibiotic tolerance in Mycobacterium tuberculosis

A 3-year Department of Medicine PhD studentship is available to work in the laboratory of Dr Julien Vaubourgeix, in the MRC Centre for Molecular Bacteriology and Infection (CMBI) at Imperial College London. The successful applicant will be joining an internationally-renowned Research Centre, within one of the world’s top research universities.

Dr Vaubourgeix’s laboratory at the MRC-CMBI, Imperial College London, focuses on uncovering molecular mechanisms of antibiotic tolerance in mycobacteria–including the human pathogen Mycobacterium tuberculosis. Because antibiotic tolerance contributes to treatment length, treatment failure, disease recurrence, and the emergence of heritable drug resistance in tuberculosis, new drugs that preferentially target tolerant cells could improve outcomes.  Research activities, including those that comprise this studentship, will contribute to our understanding of antibiotic tolerance in Mycobacterium tuberculosis to help build a foundation for the development of such drugs.

One branch of the Vaubougeix laboratory work focuses on elucidating the role of polyphosphate (poly(P)) in mycobacterial antibiotic tolerance. Poly(P)—the synthesis of which requires ATP—is a ubiquitous anionic polymer with diverse biological functions. In E. coli, poly(P) accumulates upon amino acid restriction and complexes with the Lon protease to mediate degradation of ribosomal proteins, which fuels a response to stress. Additionally, a mutant defective in poly(P) metabolism grown to stationary phase fails to form persisters at a wild-type level when exposed to ciprofloxacin, a gyrase inhibitor. In mycobacteria, strainsof Mtb defective in poly(P) metabolism display altered susceptibility to drugs by mechanisms that remain elusive.

Preliminary studies revealed that poly(P) may serve as a molecular switch that controls entry into and exit from an antibiotic-tolerant state. The goal of this studentship will be to evaluate the molecular mechanisms by which stressed Mtb transiently redirects its ATP pool into poly(P) to drive the cell into an antibiotic-tolerant state through transcriptional and metabolic reprogramming. Another complementary goal will be to test if polyphosphate—which is a high-energy polymer—also mediates Mtb’s exit from stressed states.

Candidates will use numerous methodologies, spanning microbiology, genetics, biochemistry, mass-spectrometry and photomicroscopy. Prior experience is desirable but not essential. Candidates must be expected to have a first class or upper second class Honours degree and preferably a Master’s degree passed with merit or distinction.  Only UK or EU nationals are eligible.

The 3-year studentship covers tuition fees and provides a tax free stipend at £18,000 per annum. 

To apply, please send a copy of your CV and a cover letter describing why you are suitable for this PhD studentship to Nicola Tingley (n.tingley@imperial.ac.uk). Informal enquiries can be sent to Dr. Julien Vaubourgeix (j.vaubourgeix@imperial.ac.uk).

Application Deadline: CLOSED