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The role of collagen hierarchical structure and its degradation in periodontitis

PGR-P-1971

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 Neil Thomson
Additional supervisors
Dr Thuy Do, Dr Reem El-Gendy
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>Periodontitis is one of the most common chronic inflammatory diseases (50% of adults) and is characterized by the destruction of tooth-supporting tissues, including the periodontal ligament (PDL). Collagen, the main structural protein in PDL, plays a crucial role in maintaining connective tissue integrity. This study will investigate the influence of collagen&#39;s hierarchical organization on its degradation by matrix metalloproteases (MMPs), key enzymes implicated in periodontitis progression. &nbsp;</p> <p>Collagen is resistant to many protease enzymes but is broken down and re-modelled in the body in a controlled manner by specific matrix metalloproteases (MMPs). As well as direct bacterial protease action [1], inflammatory responses from infection [2] can induce upregulation of MMPs which alters the balance between collagen degradation and repair. It is only recently, that this potential dual effect of bacterial infection in periodontitis is beginning to be understood, where direct degradation by bacterial enzymes is augmented by inflammatory pathways. &nbsp;</p> <p>We will take a two-pronged approach by characterizing ex-vivo PDL from healthy and diseased patients alongside developing in vitro experimental models of molecular collagen assembly and degradation. In both work streams, the influence of MMP action will be investigated, mainly via high resolution microscopies, including SEM and confocal, but principally atomic force microscopy (AFM) which can both image collagen biomolecular assemblies as well as probing nanoscale mechanics [3, 4].&nbsp;</p> <p>This research will bridge the gap between molecular-scale collagen organization and its functional significance in the context of periodontitis. The findings will deepen our understanding of collagen degradation, potentially leading to the development of novel therapeutic strategies to mitigate soft tissue damage associated with oral infections.</p> <h5>Aims &amp; objectives:</h5> <p>To understand from the molecular level how the density and organization of collagen hierarchies influence the ability of MMPs to degrade PDL.&nbsp;</p> <ul> <li>Develop an in vitro model of collagen assembly and degradation to determine how density and organisation affects MMP action.&nbsp;</li> <li>Characterise PDL structure by a multi-modal microscopy approach (AFM, SEM, confocal).&nbsp;</li> <li>Compare the effects of controlled MMP exposure on PDL and model collagen assemblies.&nbsp;</li> <li>Determine the bulk and nanoscale mechanics of PDL and the collagen models before/after MMP treatment.&nbsp;</li> <li>To develop a new working hypothesis of how MMPs interact with and degrade dense and highly ordered collagen structures.&nbsp;</li> </ul> <h5>References:</h5> <ol> <li>N Dam&eacute;-Teixeira, CCF Parolo, M Maltz, AG Rup, DA Devine, T Do (2018) Gene expression of bacterial collagenolytic proteases in root caries. Journal of Oral Microbiology 10 (1), 1424475&nbsp;</li> <li>NMS Hussein, JL Meade, H Pandit, E Jones, R El-Gendy (2021) The effect of diabetes mellitus on IGF Axis and stem cell mediated regeneration of the periodontium. Bioengineering 8 (12), 202&nbsp;</li> <li>CA Grant, DJ Brockwell, SE Raford, NH Thomson (2008) Effects of hydration on the mechanical response of individual collagen fibrils. Applied Physics Letters 92, 233902.&nbsp;</li> <li>CA Grant, DJ Brockwell, SE Raford, NH Thomson (2009) Tuning the elastic modulus of hydrated collagen fibrils. Biophysical Journal 97 (11) 2985.</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. 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>