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Polyvalent Multifunctional Nanoparticles to Address Resistance Bacteria

PGR-P-104

Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
Country eligibility
International (open to all nationalities, including the UK)
Funding
Competition funded
Supervisors
Professor Dejian Zhou
Schools
School of Chemistry
<h2 class="heading hide-accessible">Summary</h2>

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&rsquo;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&rsquo;Neil, FBS). The earliest start date for this project will be 1 October 2020.

<h2 class="heading">How to apply</h2>

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://www.leeds.ac.uk/info/130206/applying/91/applying_for_research_degrees">University&#39;s website</a>. Please state clearly in the research information section&nbsp;that the research degree you wish to be considered for is &lsquo;Polyvalent Multifunctional Nanoparticles to Address Resistance Bacteria&rsquo; as well as&nbsp;<a href="https://physicalsciences.leeds.ac.uk/staff/199/professor-dejian-zhou">Dr Dejian Zhou</a> as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>We welcome 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.</em></p>

<h2 class="heading heading--sm">Entry requirements</h2>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

<h2 class="heading heading--sm">English language requirements</h2>

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

<h2 class="heading">Funding on offer</h2>

<p><strong>Self-Funding Students</strong></p> <p><strong>Funding Eligibility</strong></p> <p><strong>UK/EU</strong> &ndash;&nbsp;Leeds Doctoral Scholarship Award paying Academic Fees and Maintenance matching EPSRC rate of &pound;15,009 per year for 3 years, Lowson Research Scholarship&nbsp;paying Academic Fees and Maintenance at a fixed rate of &pound;14,000 per year for 3 years, School of Chemistry Scholarship award paying Academic Fees and Maintenance matching EPSRC rate of &pound;15,009 per year for 3 years.&nbsp; Alumni Bursary is available to previous University of Leeds graduates offering 10% discount on Academic Fees.</p> <p><strong>International Students</strong> &ndash;&nbsp;China Scholarship Council-University of Leeds Scholarship Award paying Academic Fees for 3 years,&nbsp;School of Chemistry Scholarship award paying Academic Fees for 3 years, Commonwealth Scholarship and Commonwealth Split Site Scholarships.&nbsp; Alumni Bursary is available to previous University of Leeds graduates offering 10% discount on Academic Fees.</p>

<h2 class="heading">Contact details</h2>

<p>For further information regarding your application,&nbsp;please contact Doctoral College Admissions by&nbsp;email: <a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions</a><a href="mailto:EMAIL@leeds.ac.uk">@leeds.ac.uk</a>, t: +44 (0)113 343 5057.</p> <p>For further information regarding the project, please contact Dr Dejian Zhou by email:&nbsp;&nbsp;<a href="mailto:D.Zhou@leeds.ac.uk">D.Zhou@leeds.ac.uk</a></p>


<h3 class="heading heading--sm">Linked funding opportunities</h3>