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(BBSRC DTP) Engineering heterotrimeric collagens with defined chain register for tissue regeneration applications


   Faculty of Biology, Medicine and Health

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  Dr J Bella, Prof C Baldock, Dr Steven Richardson  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Collagens are the main components of connective tissues and play a critical role in providing shape stability, mechanical strength and elasticity to animal organisms. Importantly, collagens interact with cell-surface receptors and other components of the extracellular matrix via specific binding sites. Collagen genetic defects have an impact on collagen function and result in connective tissue diseases of diverse severity. Collagens of both natural and synthetic origin offer interesting possibilities for the design of scaffolds for 2D and 3D cell culture in tissue regeneration applications. Collagens can be formed by identical (homotrimers) or different chains (heterotrimers). Type I collagen, the most abundant in connective tissues, is a heterotrimer. Collagen types IV and VI are also heterotrimers. The topological arrangements of the three chains in heterotrimeric collagens have implications for the correct alignment of their cell recognition sites, but there is limited or contradicting experimental evidence on the precise details of these arrangements. We have recently devised a system for the recombinant production of heterotrimer collagens. The first aim of this project is to use this system to generate engineered, chimeric collagen model proteins to investigate the impact of specific heterotrimer collagen arrangements in cell adhesion. We expect to resolve long-standing questions on the chain arrangements of natural heterotrimer collagens, and we also anticipate to discover new arrangements with improved cell adhesion characteristics. The second aim is to incorporate the best performing engineered collagens into hydrogels and to test their efficacy as scaffolds for 2D and 3D culture of multipotent mesenchymal stem cells (MSCs). 

The successful PhD candidate will join a multidisciplinary team with complementary expertise in multiple areas of biochemistry, molecular, cellular and structural biology, and biomaterial characterisation. All members of the supervisory team have an active interest in the molecular details of collagen function and in the development of new biomaterials for tissue regeneration applications. This project should be able to provide definite answers to some long-standing questions on collagen biology and, futhermore, it has the potential for generating new, better, more efficacious collagen-modified hydrogels for use as substrates for MSC culture.

Eligibility 

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.  

Before you Apply 

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.  

How To Apply 

To be considered for this project you MUST submit a formal online application form - full details on eligibility how to apply can be found on the BBSRC DTP website https://www.bmh.manchester.ac.uk/study/research/bbsrc-dtp/  

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team [Email Address Removed]  

Equality, Diversity and Inclusion  

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/  


Funding Notes

Studentship funding is for 4 years. This scheme is open to both the UK and international applicants. We are only able to offer a limited number of studentships to applicants outside the UK. Therefore, full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.
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