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Polymeric Micro- & Nano- Bubbles for Tackling Antimicrobial Resistance

PGR-P-1110

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Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
Project start date
Saturday 1 October 2022
Country eligibility
UK only
Funding
Competition funded
Source of funding
University of Leeds
Supervisors
Professor Stephen Evans and Dr Zhan Ong
Schools
School of Physics and Astronomy
<h2 class="heading hide-accessible">Summary</h2>

Staphylococcus aureus (S. aureus) is a bloodstream infection that has mortality rates of 17-46% and is a daily occurrence, with over 12,700 cases in England per year. It is a significant cause of hospital-acquired infection and leads to extended hospitalisation, at an estimated cost per patient of &pound;8k pa. S. aureus forms biofilms, a complex mixture of biopolymers and bacterial cells, on internal organ surfaces, implants, and vasculature. The biofilm structure shields most bacteria from any antibiotics leading to poor efficacy in the treatment of infection whilst having adverse effects on the microbiome. This poor localised delivery coupled with the emergence of antimicrobial resistance means that new approaches are needed to continue treating such infections. <br /> <br /> In Leeds, we have used ultrasound (US) waves to burst tiny bubbles coated with drugs, to treat tumours effectively.<br /> 1. We have also developed some novel drugs, antimicrobial peptides (AMPs), that are selective at killing bacteria whilst leaving human cells intact.<br /> 2. However, these drugs often get broken down by enzymes in the bloodstream before reaching the infection site reducing their efficacy. <br /> <br /> In the project outlined here, we propose to protect the AMPs by hiding them in a polymeric shell surrounding the bubbles. Ultrasound will then be used to trigger the release of the drug are the site of infection by bursting the bubbles. Further, in addition to the localised delivery of drugs, we will investigate the additional benefit of physically disrupting the biofilms using US to enhance drug delivery deeper into the biofilms and for the treatment of released &lsquo;planktonic&rsquo; bacterium. <br />

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

<p>Specifically, you will:&nbsp;</p> <ol> <li>Evaluate microfluidic and alternative approaches to create microbubbles consisting of a fluorocarbon or oxygen gas core with a shell made of alternate layers of a short antimicrobial peptide (IK8, or related) and polyelectrolyte (poly-L-lysine (PLL) or poly-L-glutamic acid (PGA)).&nbsp;</li> <li>Evaluate the structure and stability of the microbubble using particle sizing and optical techniques as a function of the number of (bi)layer coatings.</li> <li>Evaluate drug loading using spectroscopic methods</li> <li>Determine ultrasound MB characteristics and drug release profiles.</li> <li>Grow&nbsp;<em>S. aureus</em>&nbsp;biofilm infections in microfluidic devices</li> <li>Perform and evaluate ultrasound/MB treatments of&nbsp;<em>S. aureus</em>&nbsp;biofilms</li> </ol> <p>You will be part of a larger multidisciplinary team working between Physics, Medicine and Engineering.&nbsp;&shy;</p> <p><strong>&shy;&shy;&shy;References</strong></p> <ol> <li>Ingram N, et al.&nbsp;<em>Theranostics</em>&nbsp;2020;10(24):10973-92. DOI: 10.7150/thno.49670 [published Online First: 2020/10/13]&nbsp;</li> <li>Ong Z, et al.<em>&nbsp;Adv. Funct. Mater.</em>&nbsp;(2013), 23(29), 3682</li> </ol>

<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 Physics &amp; Astronomy FT</strong></em>&nbsp;in the research information section&nbsp;that the research degree you wish to be considered for is <em><strong>Polymeric Micro- &amp; Nano- Bubbles for Tackling Antimicrobial Resistance</strong></em> as well as&nbsp;<a href="https://eps.leeds.ac.uk/physics/staff/4107/professor-stephen-evans">Professor Stephen Evans</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 class="MsoNoSpacing">A highly competitive School of Physics &amp; Astronomy Studentship consisting of the award of full academic fees at the Home fee rate together with a maintenance grant of &pound;16,062 in session 2022/23 for 3 years.<br /> <br /> This opportunity is open to UK applicants only. All candidates will be placed into the School of Physics &amp; Astronomy Studentship Competition and selection is based on academic merit.<br /> <br /> The&nbsp;<a href="https://www.ukcisa.org.uk/">UKCISA</a>&nbsp;website will be updated in due course with information regarding Fee Status for Non-UK Nationals starting from September/October 2021.</p> <p>&nbsp;</p>

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

<p>For further information about your application, please contact Doctoral College Admissions<br /> e:&nbsp;<a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions@leeds.ac.uk</a>, t: +44 (0)113 343 5057.</p> <p>For further information about this project, please contact Professor Stephen Evans:&nbsp;&nbsp;<a href="mailto:S.D.Evans@leeds.ac.uk">S.D.Evans@leeds.ac.uk</a></p>