Polyvalent Multifunctional Nanoparticles to Address Resistance Bacteria

Type of project

Competition funded PhD projects

Supervisor(s)

Contact Dr Dejian Zhou to discuss this project further informally.

Project description

The emergence of antibiotic resistant bacteria, e.g. methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) has created a major global health problem, affecting millions of patients worldwide.[1] For example, vancomycin (Van) is a potent antibiotic widely used for treating Gram-positive bacterial infection. Van specifically binds to bacteria cell wall mucopeptide terminal D-Ala-D-Ala residues by forming five H-bonds which sterically prevents cell-wall cross-linking and inhibit microbial growth. Mutation of a single amino acid residue from D-Ala-D-Ala to D-Ala-D-Lac in VRE deletes a single H-bond, reducing its Van binding affinity by ~1000 fold and rendering Van therapeutically useless.[2] By linking two Vans together, Van dimers have shown enhanced potency against VRE,[3] although its potency still need to be further improved to meet the clinical need.

This project aims to develop a polyvalent multifunctional nanoparticle (PMN) strategy to address the bacterial antibiotic resistance problem. Using Van as a model antibiotic, we will create multivalent display of Van on the nanoparticle surface which can bind simultaneously to multiple D-Ala-D-Lac residues on the VRE surface, greatly enhance its binding affinity and overcome VRE’s resistance mechanism. Meanwhile, the unique chemico-/physical properties (e.g. photothermal for nanorod)[4] and intrinsic anti-bacterial property of nanoparticles (e.g. silver)[5] will be further combined to offer potent multi-modal anti-bacterial action.

Specifically, this project will,

1) synthesise and characterise lipoic acid-PEG-based multi-functional ligands;

2) synthesise and characterise nanoparticles of different size and shape;

3) investigate how particle size, shape and surface chemistry determine its anti-bacterial potency;

4) prepare polyvalent Van-nanoparticles and evaluate the valency, shape and size-dependence on anti-bacterial potency;

5) investigate the potency of combined multimodal treatment against resistant bacteria (e.g. VRE, with Dr Alex O’Neil, FBS).

Entry requirements

Applications are invited from candidates with or expecting a minimum of a UK upper second class honours degree (2:1), and/or a Master's degree in a relevant subject. If English is not your first language, you must provide evidence that you meet the University’s minimum English Language requirements: http://www.leeds.ac.uk/info/123100/admissions/143/entry_requirements

Additional staff contact

Dr Alex O'Neil (A.J.ONeill@leeds.ac.uk)

How to apply

Formal applications for research degree study should be made online through the university's website. Please state clearly in the research information section that the PhD you wish to be considered for is the ‘Polyvalent Multifunctional Nanoparticles to Address Resistance Bacteria’ as well as Dr Dejian Zhou as your proposed supervisor.

We welcome scholarship applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates.  All scholarships will be awarded on the basis of merit.