Objective
The aim of this project is to investigate the molecular architecture of retrotransposon virus-like particles (VLPs) and evaluate the influence of particle structure on transposition. This novel structure/function approach will extend our current understanding of retrotransposon and, by analogy, retrovirus biology. This study may also allow the development of effective therapies for pathogenic retroelement such as the human immunodeficiency virus (HIV) and the development of new gene delivery systems. I will use the yeast Tyl element as my experimental system. The first step of my work will consist in further determination of the key residues involved in Ty sub-units interactions by site directed mutagenesis. This strategy will lead to the production of a monomeric pl protein suitable for crystallography. Simultaneously the steps of VLP assembly will be investigated and the intermediate multimer will be defined. In order to complete the structural analysis of the VLPs, I will map the Ty RNA binding site within p 1 and analyse the kinetics of RNA packaging using surface plasmon resonance technology. Finally, TYA mutations preserving particle formation and RNA packaging will be introduced in a full length Ty element and assayed for transposition in vivo. These experiments will relate our studies to the biology of Ty.
Fields of science
- natural sciencesbiological sciencesmicrobiologyvirology
- natural sciencesearth and related environmental sciencesgeologymineralogycrystallography
- medical and health scienceshealth sciencesinfectious diseasesRNA virusesHIV
- natural sciencesbiological sciencesgeneticsmutation
- natural sciencesbiological sciencesgeneticsRNA
Call for proposal
Data not availableFunding Scheme
RGI - Research grants (individual fellowships)Coordinator
OX1 3QU Oxford
United Kingdom