About the Project
New antimicrobial agents are urgently needed in order to combat the threat of antibiotic resistance. Nisin, a complex polycyclic peptide, is a promising lead. It binds with high selectively to bacterial lipid II to rupture the cell membrane via nisin-lipid II pores [1]. However, to exploit this remarkable activity for developing new simple antimicrobial agents, a thorough understanding of nisin’s structure-function relationship is necessary. The key questions are: how does nisin’s structure influence the mechanism and kinetics of pore formation; and what is the detailed architecture of the pore?
In this project, the student will address these important challenges by synthesising simplified nisin-like peptides and studying their bactericidal activity and biophysical properties. The starting point are recently created simplified nisin-like peptides in which the lipid II-binding motif of nisin (residues 1-12) is conjugated to linear pore-forming peptides [2]. These hybrid peptides have good activity against Gram-positive bacteria. Input for the design of simple peptides also comes from a recent solid-state NMR study of the nisin-lipid II pore which suggests that structures such as one of nisin’s rings (C) may be critical for pore formation, whilst the C-terminal sequence may be unstructured [1]. Our aim is to create a platform of nisin variants with linear, circular or shortened peptides to identify those structural components essential for pore forming and bactericidal activity. To study lipid II-binding and pore-forming, fluorescence binding assays and nanopore recordings will be used [3].
The requirement for this studentship is a first class or upper second-class honours degree (MSci, MChem) or equivalent. Applications, including a cover letter and full and up-to-date CV, together with the names, addresses and email addresses of two academic referees should be sent as soon as possible to Prof Tabor ([Email Address Removed]) Informal enquiries may also be made with Prof Tabor or Prof Howorka ([Email Address Removed]). Suitable candidates will be required to complete an electronic application form at http://www.ucl.ac.uk/prospective-students/graduate/apply. Any admissions queries should be directed to Dr Jadranka Butorac ([Email Address Removed]).
More about research can be found at:
https://www.ucl.ac.uk/chemistry/people/professor-alethea-b-tabor
www.howorkalab.com
References:
[1] J. Medeiros-Silva et al., Nature Commun. 2018, 9, e3963
[2] S. A. Mitchell et al., Bioorg. Med. Chem. 2018, 26, 5691
[3] J. R. Burns et al., Nature Nanotechnol. 2016, 11, 152.
Continue with Facebook
