Dr Andrew Tuplin

Photo credit Andy Murray. Used under a Creative Commons license.

Introduction

Research in my group is focused on investigating molecular mechanisms by which structured RNA, encoded by mosquito transmitted arbovirus genomes, act as dynamic RNA-switches - controlling critical aspects of virus replication through switching conformation and interactions. Specifically, we are interested in how such mechanisms are mediated by alternative interactions with host/viral proteins and microRNA, within mosquito and human host cells.  As well as advancing our understanding of fundamental mechanisms by which RNA arboviruses control different aspects of their replication cycle, we are interested in the potential of such RNA interactions as therapeutic targets.

Current major projects

• Structure and function of dynamic RNA pseudoknots in RNA viruses
• Dynamics of viral RNA structure and host-cell factor interactions
• Intracellular mapping of dynamic RNA structures/interactions in real time virus infection
• RNA structure as a therapeutic drug target

Detailed research programme

Structural and mechanistic analysis of RNA replication elements in arbovirus genomes

We have an active program of research utilising a range of cutting-edge molecular virology, genomics, quantitative proteomics, structural and cell biology approaches to investigate mechanisms by which viruses utilise structured RNA to control replication and translation of their genomes. Specifically, our research is focused on emerging RNA arboviruses - including Chikungunya, Dengue and Zika viruses – investigating how interactions between viral RNA structures, host-cell proteins and non-coding RNA provide temporal control to different stages of the virus life cycle. The goal of our research is to provide greater understanding of the virus replication cycle, in order to develop attenuated vaccines and novel antiviral targets.

SHAPE constrained thermodynamic model of functional RNA elements within
the Chikungunya virus genome. Kendall et al. Nucleic Acids Research (2019)