(BBSRC DTP) Characterisation of the pro-peptide region in regulating collagen homeostasis

Collagen-I (‘collagen’ from hereon) is the most abundant protein in the human body (circa 25% of total protein mass), providing structure to organs with very different functions (e.g. tendons vs lungs). Collagen deposition is a tightly controlled process; dysregulation underpins many pathologies and age-related conditions, including fibrosis, heart disease, and poor wound-healing. Genetic mutations in collagen leads to connective tissue disorders such as osteogenesis imperfecta and Ehlers Danlos syndrome. Despite collagen’s fundamental importance, therapeutics for diseases associated with collagen have been lacking, due to conceptual hurdles in understanding how collagen is assembled/removed. Closing these knowledge gaps forms the basis of this project. 

Previously we have found that 1) collagen homeostasis is controlled by the circadian rhythm1), 2) protomeric collagen secretion is separately controlled to fibrillogenesis, and 3) enhanced endosomal recycling may drive fibrotic progression2. Preliminary data in the lab also indicates a previously uncharacterised function for the propeptide region in regulating collagen-I homeostasis.  

Using a combination of CRISPR-Cas9 genome editing (e.g. endogenous protein tagging3,4), protein structural analyses (e.g. crystallography), protein biochemistry (e.g. nanobody screening), in vitro 2D/3D cell culture systems and in vivo mouse models, this PhD project aims to characterise the propeptide region of collagen-I, and further interrogate the molecular mechanisms to how collagen-I homeostasis is regulated by this peptide.

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]  

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