Design and Characterisations of Novel Antimicrobial Biomaterials

University of Manchester

Department of Physics and Astronomy

Project Description

Self-assembled nanobiomaterials are becoming an important research theme due to their potential in infection control and wound care, gene and cell delivery, biodevices and tissue regeneration. Nanostructures such as nanorods, nanobelts, nanofibers and nanotubes can be readily formed through self-assembly from designed short peptides. A particularly interesting group of these short peptides are those containing cationic charges as they can kill pathogenic microbes by binding to microbial membranes and causing structural disruptions. These antimicrobial peptides (AMPs) usually contain 10-14 natural amino acids and are typically amphiphilic, i.e., containing both hydrophobic and cationically charged portions. Whilst AMP molecules undertake self-assembly whilst binding to different cell membranes, a fundamental challenge lies in understanding how to balance their self-interaction against their membrane binding capacity through sequence design.

Various membrane models, e.g., spread lipid monolayers, supported lipid bilayers and small unilamellar vesicles, have been developed to facilitate measurements from atomic force microscopy, electron microscopy, neutron reflection and scattering to probe structural changes across different membranes before and after AMP attack. In an interdisciplinary environment, you will learn to design AMPs from natural amino acids, to improve their antimicrobial efficacy whilst retaining their biocompatibility to host cells and to combine neutron experiments with computer modelling to visualise in-membrane nanostructuring.

In this project, you will put soft matter and biological physics to the benefit of advancing antimicrobial biomaterials. Characterisations of AMP binding to microbial and mammalian cell membranes could help establish the relation between selective AMP attacks to different cell membranes and cytotoxicity. An upcoming challenge in developing these AMP nanobiomaterials is to assess their early immune responses, as any intended application should not elicit undesired effects or cause unnecessary damage to the host cells. These studies will help further develop AMPs to the next level of our joint biophysics and biomaterials research.

Suitable candidates would have a background in Physics, Chemistry, molecular biosciences or equivalent, and a keen interest in undertaking the challenges through interdisciplinary work. We welcome both home and overseas students to apply. Highly qualified home candidates will be selected to bid for BBSRC DTP studentship.

Funding Information

This is a self-funded project. The fees for this programme beginning in academic year 2022-23 are not yet available. Please check back for updates in the near future.

Eligibility Requirements

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.

Application Process

Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.

Supplementary Information

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.manchester.ac.uk/connect/jobs/equality-diversity-inclusion/

References

  1. Unexpected role of achiral glycine in determining the suprastructural handedness of peptide nanofibrils, Wang, M.H.; Zhao, Y.R.; Zhang, L.M.; Deng, J.; Qi, K.; Zhou, P.; Ma, X.Y.; Wang, D.; Li, Z.; Wang, J.Q.; Yang, J.; Lu, J.R.; Zhang, J.; Xu, H., ACS Nano 2021, 15, 10328-10341. DOI 10.1021/acsnano.1c02547
  2. Structural disruptions of the outer membranes of Gram-negative bacteria by rationally designed amphiphilic antimicrobial peptides, Gong, H.N.; Hu, X,Z,; Liao, M.R.; Fa, K.; Ciumac, D.; Clifton, L. A.; Sani, M-A.; King, S.M.; Maestro, A.; Separovic, F.; Waigh, T.A.; Xu, H.; McBain, A.J.; Lu, J. R., ACS Appl. Mater.Interface 2021, 13, 16062-16074. DOI: 10.1021/acsami.1c01643
  3. How do self-assembling antimicrobial lipopeptides kill bacteria? Gong, H. N.; Sani, M-A.; Hu, X.Z.; Fa, K.; Hart, J.W.; Liao, M.R.; Hollowell, P.; Carter, J.; Clifton, L.A.; Campana, M.; Li, P.X.; King, S. M.; Webster, J.R.P.; Maestro, A.; Zhu, S.Y.; Separovic, F.; Waigh, T. A.; Xu, H.; McBain, A. J.; Lu, J.R., ACS Appl. Mater. Interface 2020, 12, 55675-55687. DOI: 10.1021/acsami.0c17222
  4. Nanoribbons self-assembled from short peptides demonstrate the formation of polar zippers between β-sheets, Wang, M.; Wang, J.Q.; Zhou, P.; Deng, J.; Zhao, Y.R.; Sun, Y.W.; Yang, W.; Wang, D.; Li, Z.Y.; Hu, X.Z.; King, S.M.; Rogers, S.E.; Cox, H.; Waigh, T.A.; Yang, J.; Lu, J.R.; Xu, H., Nature Communications 2018, 9, Article number: 5118. DOI: 10.1038/s41467-018-07583-2
  5. Neurturin regulates the lung-resident macrophage inflammatory response to viral infection, Connolly, E.; Morgan, D.J.; Franklin, M.; Simpson, A.; Shah, R.; Brand, O.J.; Jagger, C.P.; Casulli, J.; Mohamed, K.; Grabiec, A.M.; Hussell, T., Life Sci. Alliance 2020, 3(12), e202000780 . DOI: 10.26508/lsa.202000780
  6. Membrane-Associated Auxiliary Factors AuxA and AuxB Modulate beta-lactam Resistance in MRSA by stabilizing Lipoteichoic Acids, Mikkelsen, K.; Sirisarn, W. Alharbi, O.; Alharbi, M.; Liu, H.Y.; Nohr-Meldgaard, K.; Mayer, K.; Vestergaard, M.; Gallagher, L.A.; Derrick, J.P.; McBain, A.J.; Biboy, J.; Vollmer, W.; O’Gara, J.P.; Grunert, T.; Ingmer, H.; Xia, G.Q., Int. J. Antimicrob. Agent 2021, 57(3), Article Number 106283, DOI:10.1016/j.ijantimicag.2021.106283

To apply for this PhD, please email J.Lu@manchester.ac.uk.

Before sending your email, please double check you have followed all guidelines in this listing and have included a reference number if asked to do so.

Overview
  • Supervisor Name
    Prof J Lu, Prof T Hussell, Prof Jeremy Derrick
  • Deadline
    Open all year round
  • Funding Type
  • Subject(s)
Location