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: 1st April 2019


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: 1st April 2019 


CMBI Clinical PhD Programme

The CMBI Clinical Research Training Fellowship is aimed at clinically qualified professionals (usually at speciality Registrar level) with training in microbiology and/or infectious diseases, or possible other infection related specialities such as intensive care, gastroenterology or respiratory medicine, who wish to undertake a PhD. Specifically, the focus will be on providing future clinical academics with the knowledge and analytical skills that will enable them to pursue high quality and clinically relevant independent research in the field of bacterial infection biology.

Applications are invited from exceptional medical graduates who demonstrate a commitment to a research career and aspire to become the next generation of clinical academic leaders to join our prestigious PhD Fellowship Programmes.

There are two Fellowships available, based at the South Kensington campus, providing an ideal base for those wishing to pursue a career in academic clinical science. Applicants do not require prior laboratory experience though this would be desirable. Applicants are also welcome to propose topics in bacterial infection biology that are suitable for PhD study and complement ongoing research programmes in the CMBI.

The Fellowships will be full-time and fixed term for three years, part time options will be considered. The scheme funding covers clinical salary, PhD registration fees at the UK/EU rate, College fees, associated project costs and general training costs.

Applicants must be GMC registered, fully qualified medical doctors in training in the UK, and at Core Training level or above, in any specialty. The fellowships will be fully funded for three years and the PhD is expected to be completed within this period, after which the post holder will return to their postgraduate clinical training.

Application deadline: CLOSED 


PhD Studentship in Bacterial Pathogenesis and Infection
By collaborating extensively with Imperial College-associated hospitals, centres of research excellence and industry, the CMBI aims to understand molecular and structural mechanisms underlying bacterial pathogenesis, host immunity and antimicrobial resistance. This knowledge is then exploited to develop novel therapeutic approaches to combat bacterial infections.

Up to four fully funded, 3.5-year PhD studentships are available to commence in October 2019. The studentships are open to UK and EU nationals and include home/EU tuition fees and a stipend of £18,000 per year. Please note that EU nationals must have lived in the UK for at least three years prior to the start of the studentship (including for the purpose of full-time education). Applicants who do not meet these eligibility requirements will not be considered.

Successful candidates will have or expect to gain 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. Applicants are requested to send a full CV (including the names and email addresses of at least two academic referees) and a personal statement outlining how a PhD degree will impact upon their career aspirations. Applicants are also requested to identify two projects (indicating order of preference) from this list for which they wish to be considered.

Application deadline: CLOSED

Enquiries

For informal enquiries relating to the above opportunities, please contact Professor Ramesh Wigneshweraraj.

For general information on postgraduate study at Imperial College please see Research opportunities.


CMBI PhD Studentship : Structural analysis of the Legionella pneumophila type IV secretion system by single particle cryo-electron microscopy.

A 3.5-year MRC funded PhD studentship is available to work in the laboratory of Dr Tiago Costa, in the 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.  The studentship covers tuition fees and provides a tax-free stipend of £18,000 per year.

About the project
Legionella pneumophila, (the causative agent of Legionnaires' disease) developed a specialized type IV secretion system (T4SS), to transport >300 toxins, into host cells (Costa et al, Nat Rev Micro, 2015). Some of the characterized translocated toxins play a critical role in hijacking host cellular pathways to establish the intracellular niche where the bacteria survive, replicate and ultimately cause disease.

The goal of the project is to investigate the atomic structure of the L. pneumophila T4SS using cutting-edge single particle cryo-electron microscopy (cryo-EM) (Costa et al, Methods in Molecular Biology, 2017). The near-atomic details obtained from the 3D structure will provide unique insights into how toxins are recruited by the secretion system, how is the secretion system gated, and which is the toxins route within the secretion system. The project will pave the way for rational design of drugs that will abolish toxin secretion preventing bacterial survival and disease.  

The project will provide training in the biochemical isolation and characterization of large membrane protein complexes, cutting-edge single particle cryo-EM data collection and processing (Costa et al, Cell, 2016). This work will take advantage of the state-of-the-art electron microscopy infrastructures located at the Francis Crick Institute and Diamond Light Source.

About the candidate
The candidates should have a strong background in protein biochemistry and an interest in bacterial secretion systems. Prior experience with cryo-electron microscopy is desirable but not essential.

Candidates must 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 who have been resident in the UK for the last 3 years are eligible.  To apply, please send a copy of your CV, a cover letter describing why you are suitable for this PhD studentship.  

Application deadline: CLOSED

 

Enquiries

For informal enquiries relating to the above opportunities, please contact Dr Tiago Costa 

For general information on postgraduate study at Imperial College please see Research opportunities.