Epigenetic regulation of collagen synthesis

Collagen is an important structural component of many tissues but collagen synthesis can become severely dysregulated in ageing and chronic disease. Organ fibrosis and age-related sclerosis of bones, joints and connective tissues, resulting from excessive collagen production cause huge clinical problems and effective treatments are limited. The epigenetic mechanisms contributing to over-production of collagen have not been well characterised but can include alterations to DNA methylation patterns and histone modifications as well as loss of microRNAs that negatively regulate collagen synthesis.

This project will focus on epigenetic regulation of the most abundant collagen (type I), which is the product of the COL1A1 and COL1A2 genes. TGF-beta is a key master-regulator of type I collagen synthesis in inflammation and fibrosis and we have observed an age-dependent effect of TGF-beta on COL1A1 and COL1A2 mRNA levels that is linked to the synthesis of abnormal non-degradable type I collagen. This project will investigate epigenetic changes that determine how cells produce type I collagen in response to TGF-beta in their environment. The work will involve analysis of cultured cells and fibrotic tissue samples (e.g. fibrotic liver). Training in quantitative RT-PCR, metabolic labelling and biochemical collagen assays will be provided. You will also learn how to implement cutting-edge techniques for epigenetic analysis of cells and tissues, such as pyrosequencing, chromatin immunoprecipitation and transfection of microRNA mimics and antagomirs. You will be guided to draft applications for ethical approval for analysis of human samples and will interact with clinicians and hospital staff during the project.

The Institute of Ageing and Chronic Disease is fully committed to promoting gender equality in all activities. In recruitment we emphasize the supportive nature of the working environment and the flexible family support that the University provides. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.

Candidates should hold or be expected to obtain a First or Upper Second class Honours degree or a Master’s degree in a relevant Biological subject, such as Biochemistry, Molecular Biology, Cell Biology or Biomedical Sciences. If English is not your first language you must have IELTS 6.5, or equivalent, with no component below 5.5.

Candidates with previous laboratory-based research experience, writing scientific reports in English and/or a Master’s degree are preferred.

Enquiries to: Dr Elizabeth Laird [Email Address Removed]

To apply please provide details of your funding and email your CV along with a covering letter to [Email Address Removed]. Please copy the application email to [Email Address Removed].