Unravelling the structural and functional role of Base-J in kinetoplastids: an integrated chemical biological approach
Supervisors:
Glenn A. Burley, Department of Pure and Applied Chemistry, University of Strathclyde
James Cotton, School of Biodiversity, One Health and Veterinary Medicine, University of Glasgow
Richard McCulloch, School of Infection and Immunity, University of Glasgow
Summary:
Trypanosomatids are protozoan parasites, causing diseases with limited treatment options, highlighting the need to further understand their pathogenesis. Trypanosomatid genomes contain a range of features that are unique amongst eukaryotes. One such feature is the presence of a glycosylated nucleotide known as Base-J, which is found across all trypanosomatids and in a small number of related euglenozoans. Base-J distribution and abundance varies across species and during trypanosomatid development and, despite its prevalence in telomeres and transcription termination sites, we have a limited understanding of the range of functions provided by Base-J.
The objective of this project is to unravel the molecular basis of how Base-J acts in trypanosomatid genomes. The project will involve establishing efficient synthetic routes to prepare Base-J nucleotides and incorporate these modifications at specific sites within short (20-100 nt) and longer sequences (> 100 nt). We will establish a structure-activity profile of the molecular determinants of Base-J recognition and use this information to map how Base-J influences gene expression and other functions throughout trypanosomatid life cycles and in non-parasitic relatives. The student will gain unique inter-disciplinary training in nucleic acid chemistry, parasitology, molecular biology and genomics.