Nanomedicines to enhance delivery of RNA therapeutics in cancer therapy

RNA therapeutics are exciting new innovations for cancer treatment due to their ability to alter gene expression and encode for exogenous proteins. The recent FDA approval of 15 oligonucleotides for treatment of eye degeneration, muscular dystrophy, and liver proteinopathy, and success of the Covid-19 mRNA vaccines demonstrate the promise of such therapeutics. In cancer therapy, however, significant biological barriers are present and need to be overcome with existing nanoparticle based gene carriers. We have recently reported the use of oppositely charged polymers and amino acids as templates for silane mineralization, yielding highly uniform and multifunctional porous silica nanoparticles (PSiNPs) [1,2]. This PhD aims to develop a broadly applicable RNA delivery system with improved ability to achieve tumour penetration and avoid premature degradation.<br /> <br /> You will:<br /> 1. Study the loading of different RNA cargoes such as antisense oligonucleotides (ASO), small interfering RNA (siRNA), and messenger RNA (mRNA) into the nanocarriers<br /> 2. Evaluate the physicochemical properties of the nanoparticles using TEM, dynamic light scattering, and x-ray photoelectron spectroscopy<br /> 3. Investigate the mechanisms of cellular uptake and release of the RNA therapeutics<br /> 4. Determine the gene transfection efficiency of the nanoparticles in 2D and 3D mammalian cancer cell cultures<br /> <br /> This project will suit a self-motivated and enthusiastic student with a keen interest in developing Nanomedicines to addressing real world medical problems. You will join a multidisciplinary team working in the School of Physics, Bragg Centre for Materials Research, and School of Medicine at the University of Leeds.<br /> <br /> References:<br /> 1. G. Newham, S.D. Evans, Z.Y. Ong, Journal of Colloid and Interface Science 617 (2022) 224&ndash;235.<br /> 2. G. Newham, R.K. Mathew, H. Wurdak, S.D. Evans, Z.Y. Ong, Journal of Colloid and Interface Science 584 (2021) 669-683. <br /> <br />

<p>RNA therapeutics are exciting new innovations for cancer treatment due to their ability to alter gene expression and encode for exogenous proteins. The recent FDA approval of 15 oligonucleotides for treatment of eye degeneration, muscular dystrophy, and liver proteinopathy, and success of the Covid-19 mRNA vaccines demonstrate the promise of such therapeutics. In cancer therapy, however, significant biological barriers are present and need to be overcome with existing nanoparticle based gene carriers. We have recently reported the use of oppositely charged polymers and amino acids as templates for silane mineralization, yielding highly uniform and multifunctional porous silica nanoparticles (PSiNPs) [1,2]. This PhD aims to develop a broadly applicable RNA delivery system with improved ability to achieve tumour penetration and avoid premature degradation.</p> <p>You will:<br /> 1.&nbsp;&nbsp; &nbsp;Study the loading of different RNA cargoes such as antisense oligonucleotides (ASO), small interfering RNA (siRNA), and messenger RNA (mRNA) into the nanocarriers<br /> 2.&nbsp;&nbsp; &nbsp;Evaluate the physicochemical properties of the nanoparticles using TEM, dynamic light scattering, and x-ray photoelectron spectroscopy<br /> 3.&nbsp;&nbsp; &nbsp;Investigate the mechanisms of cellular uptake and release of the RNA therapeutics<br /> 4.&nbsp;&nbsp; &nbsp;Determine the gene transfection efficiency of the nanoparticles in 2D and 3D mammalian cancer cell cultures</p> <p>This project will suit a self-motivated and enthusiastic student with a keen interest in developing Nanomedicines to addressing real world medical problems. You will join a multidisciplinary team working in the School of Physics, Bragg Centre for Materials Research, and School of Medicine at the University of Leeds.</p> <p>References:<br /> 1.&nbsp;&nbsp; &nbsp;G. Newham, S.D. Evans, Z.Y. Ong, Journal of Colloid and Interface Science 617 (2022) 224&ndash;235.<br /> 2.&nbsp;&nbsp; &nbsp;G. Newham, R.K. Mathew, H. Wurdak, S.D. Evans, Z.Y. Ong, Journal of Colloid and Interface Science 584 (2021) 669-683.&nbsp;</p>

<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 section that you are applying for <em><strong>PhD Physics &amp; Astronomy FT</strong></em> and in the research information section&nbsp;that the research degree you wish to be considered for is <em><strong>Nanomedicines to enhance delivery of RNA therapeutics in cancer therapy</strong></em>&nbsp;as well as&nbsp;<a href="https://eps.leeds.ac.uk/physics/staff/4120/dr-zhan-yuin-ong">Dr Zhan Ong</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>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p> <p class="MsoNoSpacing">Applications will be considered on an ongoing basis. &nbsp;Potential applicants are strongly encouraged to contact the supervisors for an informal discussion before making a formal application. &nbsp;We also advise that you apply at the earliest opportunity as the application and selection process may close early, should we receive a sufficient number of applications or that a suitable candidate is appointed.</p> <p>Please note that you must provide the following documents at the point you submit your application:</p> <ul> <li>Full Transcripts of all degree study or if in final year of study, full transcripts to date</li> <li>Personal Statement outlining your interest in the project</li> <li>CV</li> <li>Funding information including alternative sources of funding that you are applying for or if you are able to pay your own fees and maintenance</li> </ul>

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.

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.

<p style="margin-bottom:12px"><strong>Self-Funded or externally sponsored students are welcome to apply.</strong></p> <p><strong>UK</strong>&nbsp;&ndash;&nbsp;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/209-leeds-doctoral-scholarships-2022">Leeds Doctoral Scholarships</a> and <a href="https://phd.leeds.ac.uk/funding/234-leeds-opportunity-research-scholarship-2022">Leeds Opportunity Research Scholarship</a> are available to UK applicants. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/102-bell-burnell-scholarship-award-awarded-by-the-iop">Bell Burnell Scholarship Award</a>&nbsp;is available to support applicants who are from groups that are currently under-represented in physics (awarded by the IOP).&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</strong> &ndash; The&nbsp;<a href="https://phd.leeds.ac.uk/funding/102-bell-burnell-scholarship-award-awarded-by-the-iop">Bell Burnell Scholarship Award</a>&nbsp;is available to support applicants who are from groups that are currently under-represented in physics (awarded by the IOP).&nbsp; &nbsp;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. <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>Important:</strong>&nbsp; Any costs associated with your arrival at the University of Leeds to start your PhD including flights, immigration health surcharge/medical insurance and Visa costs are <strong>not</strong> covered under these studentships.</p> <p>Please refer to the <a href="https://www.ukcisa.org.uk/">UKCISA</a> website for information regarding Fee Status for Non-UK Nationals.</p>

<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></p> <p>For further information about this project, please contact Dr Zhan Ong<br /> e:&nbsp;<a href="mailto:z.y.ong@leeds.ac.uk">z.y.ong@leeds.ac.uk</a></p>