Protein modifications are important in many diseases including fibrosis and cancer. In protein glycosylation carbohydrate polymers, or glycans, are covalently attached to proteins forming glycoproteins. This project will investigate the importance of protein glycosylation in liver diseases including fibrosis and cancer of the bile duct, a form of cancer that is particularly deadly and for which there is no screening test that allows early detection and treatment. Protein glycosylation controls protein trafficking, stability and folding and the glycans themselves can mediate interactions with other molecules. This can alter/mediate ligand-receptor interactions, control oncogenic signal transduction, change immune recognition, and control cell migration, cell-cell contacts, and cell adhesion. The transcriptional reprograming that occurs in cancer cells has an enormous effect on the glycoproteome and this can produce new specific glycoepitopes (carbohydrate structures that can be recognized by an antibody or other probe) which can serve as biomarkers for disease progression. Bile duct diseases including bile duct cancer, cholangitis, and fibrosis are a result of bile duct wounding and chronic inflammation and this is often accompanied by the secretion of mucins, a family of large, heavily glycosylated proteins. The glycosylation of mucins and their secretion into blood and bile is regulated by transcription factors that reprogramme gene expression during disease progression. Our aim is to use RNA sequencing and chromatin immunoprecipitation sequencing to investigate the consequences of changes in transcription factor activity during cancer progression on the expression of genes involved in protein glycosylation and mucin secretion. We will also determine how this alters the proliferation and migration of primary human bile duct cells and assess changes in protein glycosylation on the cell surface and in blood and bile using a novel patented detection technology involving fluorescent nanoparticles. We hope that this work will increase our understanding of liver diseases and particularly bile duct cancer and lead to the development of new screening methods.
Applicants should be very enthusiastic and have interests in liver disease, or cancer biology, proteomics, transcriptomics or epigenetics. They should also be interested in novel chemical engineering technologies and biomarker discovery. They should hold or expect to obtain at least an Upper Second Class Honours degree in, Biological Sciences or related subjects. How to apply Applicants are encouraged to contact Dr PS Jayaraman directly ([email protected]) to discuss the project before applying. Additional projects are available in the lab.
The Midlands Integrative Biosciences Training Partnership (MIBTP) is a BBSRC-funded doctoral training partnership between the universities of Warwick, Birmingham and Leicester. Successful applicants will be funded by the BBSRC, including UK fees and stipend. Detailed instructions for applicants, academic requirements and eligibility criteria can be found in the University of Birmingham websites: https://www.birmingham.ac.uk/research/activity/mibtp/index.aspx