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Polyvalent Multifunctional Nanoparticles to Address Resistance Bacteria

PGR-P-104

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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 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.<br /> <br /> 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 VREs 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.

<h2 class="heading hide-accessible">Full description</h2>

<p>A major limitation of current antibacterial nanomaterial research has been too&nbsp;focused on pursuing&nbsp;antibacterial potency only without or little&nbsp;consideration&nbsp;of their stability and interactions with biological media and&nbsp;renal clearance. These are key requiremens&nbsp;for real world application and clinical approval. As a result,&nbsp;most&nbsp;current&nbsp;antibacterial nanomaterials&nbsp;have little proposet of being translated into useful drugs despite high antibacterial potency in vitro. Here we will address this problem by balancing these needs at the begining of our antibacterial nanomaterials design, greatly enhancing&nbsp;their chances for&nbsp;clinical impact.</p> <p>Specifically, this project will,</p> <p>1) synthesise and characterise lipoic acid-PEG or zwitterionic based multi-functional ligands to enhance&nbsp;nanoparticle stability and reduce non-specific interactions with serum proteins and other biological compotents;</p> <p>2) synthesise and characterise nanoparticles of different sizes&nbsp;to allow for renal clearance;</p> <p>3) investigate how particle size, shape and surface chemistry determine its anti-bacterial potency;</p> <p>4) prepare polyvalent Van-nanoparticles and evaluate the valency, shape and size-dependence on anti-bacterial potency;</p> <p>5) investigate the potency of combined multimodal treatment against resistant bacteria (e.g. VRE, with Prof.&nbsp;Alex O&rsquo;Neil, FBS).</p>

<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/research-applying/doc/applying-research-degrees">University&#39;s website</a>. Please state clearly in the Planned Course of Study that you are applying for <em><strong>PHD Chemistry FT</strong></em> in the research information section&nbsp;that the research degree you wish to be considered for is <em><strong>Polyvalent Multifunctional Nanoparticles to Address Resistance Bacteria</strong></em>&nbsp;as well as Prof.<a href="https://physicalsciences.leeds.ac.uk/staff/199/professor-dejian-zhou">&nbsp;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>&nbsp;</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 or externally sponsored students are welcome to apply.</strong></p> <p><strong>UK&nbsp;students</strong>&nbsp;&ndash;&nbsp;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/209-leeds-doctoral-scholarships-2022">Leeds Doctoral Scholarships</a>,&nbsp;<a href="https://phd.leeds.ac.uk/funding/118-lund-stephenson-clarke-scholarship-2022">Lund Stephenson Clarke</a>, <a href="https://phd.leeds.ac.uk/funding/198-akroyd-and-brown-scholarship-2022">Akroyd &amp; Brown</a>, <a href="https://phd.leeds.ac.uk/funding/199-frank-parkinson-scholarship-2022">Frank Parkinson</a>, <a href="https://phd.leeds.ac.uk/funding/205-henry-ellison-charles-brotherton-research-scholarship-2022">Henry Ellison-Charles Brotherton</a> and <a href="https://phd.leeds.ac.uk/funding/204-boothman-reynolds-and-smithells-scholarship-2022">Boothman, Reynolds &amp; Smithells</a> Scholarships are available to UK applicants. &nbsp;<a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p> <p><strong>Non-UK students</strong>&nbsp;&ndash;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/48-china-scholarship-council-university-of-leeds-scholarships-2021">China Scholarship Council - University of Leeds Scholarship</a>&nbsp;is available to nationals of China. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/73-leeds-marshall-scholarship">Leeds Marshall Scholarship</a>&nbsp;is available to support US citizens. &nbsp;<a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</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 Prof.&nbsp;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 research areas</h3>