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Integration of localized electrically deciphered epigenetic profiles for enhanced stem cell therapy

PGR-P-1970

Key facts

Type of research degree
PhD
Application deadline
Wednesday 19 June 2024
Project start date
Tuesday 1 October 2024
Country eligibility
UK only
Funding
Funded
Source of funding
External organisation
Supervisors
Dr Xuebin Yang
Additional supervisors
Professor Giuseppe Tronci, Dr Thuy Do
Schools
School of Dentistry
<h2 class="heading hide-accessible">Summary</h2>

One fully funded Frederick E Hopper full-time PhD scholarship is available in the School of Dentistry for a start in October 2024. The scholarship will cover UK tuition fees and attract a stipend of &pound;19,237, subject to satisfactory progress.<br /> The award is open to full-time or part-time candidates (UK only) who meet the eligibility for a place on a PhD degree at the School of Dentistry. This project would suit a student with a microbiology or molecular biology background.<br /> Candidates whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study.

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

<h5>Project summary</h5> <p>The global regenerative medicine market size is projected to be US$197.08 billion by 2030. However, the effectiveness of these therapies are big challenge for clinical translation. Following the dawn of AI, real-time sensing and monitoring have played a crucial role in enhancing regenerative medicine technologies. This proposal seeks to combine the expertise in stem cells (Yang), biomaterials (Tronci), microbiology (Do) and bioelectrical engineering (Gao, RWTH, Germany) and aims to employ a novel cutting-edge approach in dynamic real-time sensing and monitoring with biohybrid electronics for advancing epigenetic control in stem cell differentiation, which improve the tissue engineering efficacy. This unique approach leverages our expertise in epigenetic modification [1,2] and biohybrid electronic sensors [3,4] to decipher the mechanism of human dental pulp stem cells (hDPSCs) functionality on 3D hydrogel scaffolds with photodynamic infection control capability [5]. This offers unprecedented insight into cellular dynamics, facilitates the identification of regulatory factors and critical time points, enables personalized treatment strategies, enhances drug screening, and promotes translation to clinical applications for improved bone regeneration and patient care. HDPSCs are pre-treated with histone deacetylase inhibitor (HDACi) to enhance stem cells&rsquo; cellular responses. The micro/nano-electronic &amp; fabrication technologies allow non-invasive multidimensional cell-sensor coupling and hybrid biosignal integration so that localized electric stimulation and signal recording will be delivered to guide stem cell differentiation on/in 3D hydrogel scaffolds in real-time, which will lead to a readable and programmable epigenetic control system, offering multidimensional tools to promote bespoke stem cell therapy, infection diagnosis and staining-free photodynamic infection control. &nbsp;&nbsp;</p> <h5>Aims &amp; objectives: &nbsp;</h5> <p>This project aims to combine epigenetic modification and a novel cutting-edge approach in dynamic real-time sensing and monitoring with biohybrid electronics to decipher the mechanism of stem cell functionality for enhancing the efficacy of bone tissue regeneration. &nbsp;</p> <ul> <li>Isolation and characterisation of human dental pulp stem cell from fresh sound human tooth.&nbsp;</li> <li>The effect of epigenetic modification on hDPSCs osteogenesis in monolayer and 3D culture (hydrogel).&nbsp;</li> <li>Integration of biohybrid electronic sensing system for hDPSCs study: validation and optimisation.&nbsp;</li> <li>The effect of photodynamic therapy on the infection control capability of 3D hydrogel scaffolds.&nbsp;</li> <li>Real-time monitoring of cellular/bacterial responses: sensing, stimulation, and differentiation guidance.&nbsp;</li> <li>Epigenetic analysis and epi-electric signal correlation.&nbsp;</li> <li>In In vivo testing uses animal models.&nbsp;</li> </ul> <h5>References:&nbsp;</h5> <ol> <li>Lu, W.; Ji, K.; Lawlor, L.; Saha, S.; Hempshall, A.; Jin, Y.; Yang, X.B. The effect of epigenetic reprogramming using mi192 HDAC inhibitor on enhancing the osteogenesis of human adipose-derived stem cells in vitro. Biosci Rep <strong>2023</strong>, 43.&nbsp;</li> <li>Man, K.; Mekhileri, N.V.; Lim, K.S.; Jiang, L.H.; Woodfield, T.B.F.; Yang, X.B. Mi192 induced epigenetic reprogramming enhances the therapeutic efficacy of human bone marrows stromal cells for bone regeneration. Bone <strong>2021</strong>, 153, 116138.&nbsp;</li> <li>Liang, Q.; Xia, X.; Sun, X.; Yu, D.; Huang, X.; Han, G.; Mugo, S.M.; Chen, W.; Zhang, Q. Highly stretchable hydrogels as wearable and implantable sensors for recording physiological and brain neural signals. Adv Sci (Weinh) <strong>2022</strong>, 9, e2201059.&nbsp;</li> <li>Clavaguera, S.; Raoul, N.; Carella, A.; Delalande, M.; Celle, C.; Simonato, J.P. Development of an autonomous detector for sensing of nerve agents based on functionalized silicon nanowire field-effect transistors. Talanta <strong>2011</strong>, 85, 2542-2545.&nbsp;</li> <li>Contreras, A.; Raxworthy, M.J.; Wood, S.; Schiffman, J.D.; Tronci, G. Photodynamically active electrospun fibers for antibiotic-free infection control. ACS Appl Bio Mater <strong>2019</strong>, 2, 4258-4270.</li> </ol> <h5>Other Conditions</h5> <ul> <li>Applicants must not have already been awarded or be currently studying for a doctoral degree.</li> <li>Awards must be taken up by 1st October 2024.</li> <li>Applicants must live within a reasonable distance of the University of Leeds whilst in receipt of this scholarship.</li> </ul>

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

<p>To apply for this scholarship opportunity applicants should complete an <a href="https://medicinehealth.leeds.ac.uk/faculty-graduate-school/doc/apply-2">online application form</a> and attach the following documentation to support their application.&nbsp;</p> <ul> <li>A full academic CV</li> <li>Degree certificate and transcripts of marks</li> <li>Evidence that you meet the University&#39;s minimum English language requirements (if applicable)</li> </ul> <p>To help us identify that you are applying for this scholarship project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Dentistry as your programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> <li>For source of funding please state you are applying for a&nbsp;Frederick E Hopper Scholarship</li> </ul> <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>

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

Applicants to this scholarship in the School of Dentistry should normally have an Undergraduate degree of 2:1 or above (or international equivalent) in a relevant subject area. A Master&rsquo;s degree is desirable, but not essential. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Admissions Team prior to making an application.

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

The minimum English language entry requirement for postgraduate research study in the School of Dentistry is an IELTS of 6.5 overall with at least 6.0 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.

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

<p>We are offering 1 full-time PhD scholarship in the School of Dentistry for one UK candidate, covering a maintenance grant of &pound;19,237 per year and UK tuition fees for three years, subject to satisfactory progress. The award will be made for one year in the first instance and renewable for a further period of up to two years, subject to satisfactory academic progress.&nbsp;This is one of four available projects being advertised for the one successful candidate for this scholarship.&nbsp;</p>

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

<p>For further information please contact the Faculty PGR Admissions Team</p> <p>e: <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p>