Single-molecule study of RNA splicing reactions encapsulated in lipid vesicles

Single-molecule measurements have contributed much to our understanding of conformational transitions in proteins and nucleic acids, providing an insight into reaction dynamics, establishing the presence, or not, of multiple reaction pathways and identifying the existence of rare events.

Dr Andrew Hudson, a physical chemist/ biophysicist, and Prof Ian Eperon, a molecular biologist, have been collaborating for 5+ years on the application of single molecule methods in RNA splicing – a series of reactions in which the RNA molecules transcribed initially are processed to remove long sections (called introns), leaving the protein encoding sequence.

There are many different potential alternative pathways for splicing any given RNA (some are essential for life but others are detrimental), however, the mechanism of selection of the right splice sites remains obscure. Our hypothesis is that the selection of alternative pathways for splicing depends critically on the flexibility of RNA.

This project will develop a single molecule approach that will enable the role of conformational flexibility in splice-site selection to be elucidated.

The successful candidate will employ cutting-edge techniques in biophysics. In addition to single molecule fluorescence spectroscopy, it will be necessary to learn soft matter techniques to encapsulate splicing complexes in synthetic lipid vesicles and droplet-microfluidic techniques to partition aqueous biological samples into stabilised-emulsion droplets which will allow the splicing complexes to be isolated and studied individually.

The project is a collaboration between the research groups of Dr Andrew Hudson (Department of Chemistry) and Prof Ian Eperon (Molecular and Cell Biology). Applicants should possess, or be very close to obtaining, a 1st class or 2.1 degree in Chemistry or Biochemistry, or another related field.

The candidate will work with both groups in the Henry Wellcome Building which is the home of a brand new investment at university level into The Leicester Institute for Structural and Chemical Biology (LISCB). LISCB is a cross-disciplinary entity that brings together internationally renowned research in structural biology and chemical biology at the University of Leicester into a single world-leading unit. The new Institute aims to exploit synergies in research technologies to deliver major advances in both fundamental and translational research.