About the Project
Bacterial infection is a fact of life. Antibiotics have considerably reduced mortality, but the spread of antibiotic resistance threatens to impede infectious disease control and compromise basic aspects of healthcare that we take for granted. In the UK ~44,000 deaths occur every year from untreatable bacterial infections, costing the NHS £2 billion annually.
Iron is a vital cofactor for many enzymes, and bacteria must ensure that they have an adequate supply of this essential nutrient. Upon infection by microorganisms, the animal host innate immune system typically reduces the availability of iron. In response, bacteria activate pathways for metal import, metal sparing, or metal storage to avoid stress from metal starvation. This competition for metals is termed “nutritional immunity”. Ferritin proteins are the primary iron stores in all kingdoms of life, they act to oxidise and sequester iron in a bioavailable mineral form within a hollow protein cage. Some bacteria possess heme-binding bacterioferritins, which allow the rapid mobilisation of stored iron through electron transfer via the heme group.
You will study a membrane associated bacterioferritin complex from the Gram-negative pathogen Neisseria gonorrhoeae. This pathogen has been identified as a “superbug”, with multiple strains and isolates that have become completely resistant to all last-line antibiotics. It is not surprising that this pathogen is listed by the Centre of Disease Control (USA), the World Health Organisation, and Public Health UK as a research priority.
Goals and Objectives:
1) You will produce recombinant bacterioferritin complexes, for structural and functional analyses to understand how iron is stored within the compartment.
2) You will use modern structural biology techniques, including X-ray crystallography and electron microscopy, to analyse the molecular structure of the bacterioferritin complex.
3) You will make targeted gene knockouts in Neisseria gonorrhoea of the individual bacterioferritin components to understand their role in the physiology and pathogenicity of this bacterium.
You will be based in the laboratory of the primary supervisor at Newcastle University, and work closely with co-supervisors at Durham and Newcastle.
Training will be given in basic microbiology, microbial genetics and physiology, molecular biology, and recombinant protein expression and purification. The project will make use of cryo-electron microscopy and single-particle analysis. This project would suit a candidate with a degree in microbiology, biochemistry, or chemistry. You will also have the opportunity for a 3-month industrial placement.
Informal enquiries may be made to firstname.lastname@example.org
HOW TO APPLY
Applications should be made by emailing email@example.com with a CV and a covering letter, including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project/s and at the selected University. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.
In addition to the CV and covering letter, please email a completed copy of the Newcastle-Liverpool-Durham (NLD) BBSRC DTP Studentship Application Details Form (Word document) to firstname.lastname@example.org, noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
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