The role of collagen hierarchical structure and its degradation in periodontitis

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 £19,237, subject to satisfactory progress.

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.

Candidates whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study.

Project Summary:

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’s hierarchical organization on its degradation by matrix metalloproteases (MMPs), key enzymes implicated in periodontitis progression. 

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. 

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]. 

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.

Aims & Objectives:

To understand from the molecular level how the density and organization of collagen hierarchies influence the ability of MMPs to degrade PDL. 

• Develop an in vitro model of collagen assembly and degradation to determine how density and organisation affects MMP action.
• Characterise PDL structure by a multi-modal microscopy approach (AFM, SEM, confocal).
• Compare the effects of controlled MMP exposure on PDL and model collagen assemblies.
• Determine the bulk and nanoscale mechanics of PDL and the collagen models before/after MMP treatment.
• To develop a new working hypothesis of how MMPs interact with and degrade dense and highly ordered collagen structures.

Eligibility

Applicants to this scholarship should normally have an Undergraduate degree of 2:1 or above (or international equivalent) in a relevant subject area. A Masters degree is desirable but not essential.

If English is not your first language, you must provide evidence that you meet the University’s minimum English language requirements. The minimum English language entry requirement for the Faculty of Medicine & Health is an IELTS of 6.5 overall with at least 6.0 in each component or equivalent. The test must be dated within two years of the start date of the course in order to be valid.

How to Apply

To apply for this scholarship opportunity applicants should complete an online application form and attach the following documentation to support their application. 

• A full academic CV
• Degree certificate and transcripts of marks
• Evidence that you meet the University’s minimum English language requirements (if applicable)

To help us identify that you are applying for this scholarship project please ensure you provide the following information on your application form;

• Select PhD in Dentistry as your programme of study
• Give the full project title and name the supervisors listed in this advert
• For source of funding please state you are applying for a Frederick E Hopper Scholarship

For further information please contact the Faculty PGR Admissions Team at fmhpgradmissions@leeds.ac.uk