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Engineering of broad-spectrum chimeric antibacterial lysins for use in household cleaning products


Biosciences Institute

Prof W Vollmer , Dr SL Cobb Friday, January 22, 2021 Competition Funded PhD Project (Students Worldwide)
Newcastle United Kingdom Biochemistry Bioinformatics Microbiology Molecular Biology

About the Project

Bacteria are capable of propagating in almost every environment on earth and may cause significant harm to human health. Antibiotics are crucial to control bacterial infections in medicine, but they are not suitable (or desired) to be used as disinfectants in daily life. Many household cleaning products contain quaternary ammonium salts as antibacterial agents despite their negative environmental impact. This project emerged from discussions between the PIs and scientists at Procter and Gamble (P&G) to address the need to develop alternative antibacterial strategies for household cleaning products. We will develop novel antibacterial enzymes (lysins) and evaluate whether they have the potential to replace quaternary ammonium salts in household cleaning products.

Lysins are ubiquitous in nature produced by virtually all organisms. Our own immune system produced several antibacterial enzymes (lysozyme and serum amidase), and lysins are secreted by animals, plants, fungi and bacteria themselves to fight bacterial competitors or invaders. Perhaps the best lysins (in terms of activity and stability) are produced by bacteriophages which have evolved to efficiently kill their target bacteria. However, phage-derived lysins are normally highly specific for the phage's host bacterium and are not normally active against a range of different bacteria, making them less suitable for disinfection products. In this project, we aim to engineer novel lysins that target a wide range of bacteria and are suitable for the use as environmentally friendly, biodegradable additives in household cleaning products. Hence, the project will not only generate key fundamental knowledge about the molecular architecture and activity of novel lysins, but combine this fundamental science with a real-life application.

The PhD project offers an outstanding, multidisciplinary training opportunity at the interface of microbiology, chemistry and biophysics. Training will be provided in handling bacteria, molecular gene cloning and protein production, biochemical analysis of protein interaction and enzyme activity assays, using state-of-the-art technologies. Training will be provided at the excellent research facilities of the Centre for Bacterial Cell Biology (Newcastle University), the Biophysical Sciences Institute and Chemistry Department (Durham University) and the P&G Newcastle Innovation Centre. The project will contribute to the commercial development of improved formulations for household cleaning products, and provides a unique training experience to acquire skills for a career in academic or industrial research. 

Informal enquiries may be made to

HOW TO APPLY 

Applications should be made by emailing 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 , 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.


Funding Notes

CASE studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

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5. Type VI secretion delivers bacteriolytic effectors to target cells. Nature 475, 343-347 (2011).
6. Fluorinated aromatic monomers as building blocks to control α-peptoid conformation and structure, Journal of the American Chemical Society 141 (8), 3430-3434 (2019)
7. Synthesis of Antibacterial Nisin–Peptoid Hybrids Using Click Methodology, Molecules 23 (7), 1566 (2018)
8. Peptoid Efficacy against Polymicrobial Biofilms Determined by Using Propidium Monoazide‐Modified Quantitative PCR, ChemBioChem 18 (1), 111-118 (2017)
9. Total chemical synthesis of lassomycin and lassomycin-amide. Organic & Biomolecular Chemistry 14 (19), 4534-4541 (2016)
10. The role of phosphoglycans in the susceptibility of Leishmania mexicana to the temporin family of anti-microbial peptides, Molecules 20 (2), 2775-2785 (2015)
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