Exploring Cellular Biomechanics at Calvarial Suture: A Soft-Hard Tissue Interface - Engineering - EPSRC DTP funded PhD Studentship Ref: 2964

About the award

This project is one of a number funded by the Engineering and Physical Sciences Research Council (EPSRC) Doctoral Training Partnership to commence in September 2018. This project is in direct competition with others for funding; the projects which receive the best applicants will be awarded the funding.

The studentships will provide funding for a stipend which is currently £14,553 per annum for 2017-2018. It will provide research costs and UK/EU tuition fees at Research Council UK rates for 42 months (3.5 years) for full-time students, pro rata for part-time students.

Please note that of the total number of projects within the competition, up to 15 studentships will be filled.

Supervisors
Dr. Junning Chen
Professor C Peter Winlove
Professor Peter Fratzl

Location 
Streatham Campus, Exeter

Project Description
This project investigates the calvarial suture fusion at different ages of mice and its biomechanical and physiological implication for load transfer and neurocranial growth, by combining microCT, confocal microscopy and finite element analysis.

As the most abundant cells in bone, osteocytes are the control centre to process biomechanical stimulus and to regulate remodelling events through their extensive Lacuno-Canaliculi Network (LCN). While the key factors governing the arrangement of osteocyte LCN remain unclear, mechanical loading is found capable of alternating cellular and network topology. These characteristics of LCN are found closely associated with extracellular matrix (ECM) mineralisation, through which nanoscopic mineral particles are embedded in organic collagen matrix. The different amounts, sizes, and arrangements of mineral particles contribute to bone material properties through a hierarchical structure in bone. In return, these ECM mineral conditions affect consequential remodelling events. Continuous effectors have been dedicated to understanding the interaction among biomechanical loading, LCN characteristics, and ECM mineral conditions in long bone, and their interaction is believed as indicative for pathological conditions, such as osteoporosis, osteoarthritis, and osteoarthrosis.

Compared to the emerging findings of LCN characteristics and ECM mineral conditions in long bone, very little is yet known for other types of bone, such as in calvaria. The calvaria bones are joined by fibrous sutures (Sharpey’s fibres). Not only providing the cranial flexibility during birth, this soft-hard (suture-bone) tissue interface is also the primary site of intramembranous bone growth to accommodate the rapid expansion of neurocranium through embryonic development and early postnatal growth. These sutures transmit biomechanical signals and balance the proliferation of osteogenic cells and their differentiation to form new bone. Interestingly, sutures must keep their patency from ossification to maintain their functionalities in extending calvaria bone fronts. Premature closure of sutures (craniosynostosis) by ossification affects approximately 1 out of 2000 newborns, and can lead to abnormal facial and cranial appearances; in the worse scenarios, it will cause the increased intracranial pressure leading to visual damage, sleeping disorder, masticatory malfunction, impaired mental development, and even sudden death. Another major clinical challenge is bone flap resorption and cranioplastic failure following decompressive craniectomy, affecting both infants and adults. Investigating into the mechanical stimulation-cell-mineral interaction can provide some temporal and spatial insights in suture morphogenesis and bone formation, which potentially helps elucidating possible mechanisms involving these clinical conditions.

This project is structured to answer the following two closely related fundamental questions

1) How do fibrous tissues in sutures connect the calvaria bone in a 3D manner and how is the biomechanical stimulus distribution across this tissue interface?
2) As the primary growth site, what are the spatial and temporal effects of a suture on osteocyte LCN arrangement and ECM mineralisation, along and further away from a suture?

To answer these questions, the student will be required to perform
-microCT imaging, confocal microscopy, back-scattered imaging
-image segmentation and analysis
-reverse engineering modelling
-finite element analysis for mechanical status

The student will be encouraged to travel to Max Planck Institute of Colloids and Interfaces, McGill University, and top international conferences to present the research outcome.

A successful candidate should have
-First class or good upper second-class degree in mechanical or material engineering;
-Outstanding inter-personal and communication skills to work in an interdisciplinary team and international collaborators;
-Sufficient knowledge of various types of image analysis.

This studentship will be awarded based on a competitive basis for a minimum of 3.5 years.

Entry Requirements
You should have or expect to achieve at least a 2:1 Honours degree, or equivalent, in mechanical or material engineering. Experience in medical image segmentation and finite element analysis is desirable.

If English is not your first language you will need to meet the English language requirements and provide proof of proficiency. Click here for more information and a list of acceptable alternative tests.

The majority of the studentships are available for applicants who are ordinarily resident in the UK and are classed as UK/EU for tuition fee purposes.  If you have not resided in the UK for at least 3 years prior to the start of the studentship, you are not eligible for a maintenance allowance so you would need an alternative source of funding for living costs. To be eligible for fees-only funding you must be ordinarily resident in a member state of the EU.  For information on EPSRC residency criteria click here.

Applicants who are classed as International for tuition fee purposes are NOT eligible for funding. International students interested in studying at the University of Exeter should search our funding database for alternative options.

Summary

Application deadline:10th January 2018
Value:3.5 year studentship: UK/EU tuition fees and an annual maintenance allowance at current Research Council rate. Current rate of £14,553 per year.
Duration of award:per year
Contact: Doctoral Collegepgrenquiries@exeter.ac.uk

How to apply

You will be required to upload the following documents:
•       CV
•       Letter of application outlining your academic interests, prior research experience and reasons for wishing to
        undertake the project.
•       Transcript(s) giving full details of subjects studied and grades/marks obtained.  This should be an interim
        transcript if you are still studying.
•       If you are not a national of a majority English-speaking country you will need to submit evidence of your current
        proficiency in English.  For further details of the University’s English language requirements please see
        http://www.exeter.ac.uk/postgraduate/apply/english/.

The closing date for applications is midnight (GMT) on Wednesday 10 January 2018.  Interviews will be held at the University of Exeter in late February 2018.

If you have any general enquiries about the application process please email: pgrenquiries@exeter.ac.uk.
Project-specific queries should be directed to the supervisor.

During the application process, the University may need to make certain disclosures of your personal data to third parties to be able to administer your application, carry out interviews and select candidates.  These are not limited to, but may include disclosures to:

• the selection panel and/or management board or equivalent of the relevant programme, which is likely to include staff from one or more other HEIs;
• administrative staff at one or more other HEIs participating in the relevant programme.

Such disclosures will always be kept to the minimum amount of personal data required for the specific purpose. Your sensitive personal data (relating to disability and race/ethnicity) will not be disclosed without your explicit consent.