Host cell membrane tethering during plant virus infection

Supervisors: Jens Tilsner, Huanting Liu

Project Description
Plant viruses are economically important crop pathogens and a threat to global food security. In order to successfully infect a host plant, they need to replicate their genome on cellular membranes, and then transport progeny viruses into naïve cells through membranous cell-to-cell communication channels (plasmodesmata). For both of these processes, viruses recruit and utilise cellular membrane tethering proteins which can bridge two membranes, to keep them in close proximity and facilitate lipid exchange and localised signalling [1,2]. However, it is not known exactly how viruses benefit from hijacking the cellular membrane tethering machinery [3].

This project will investigate the role of two types of tethering proteins, plant synaptotagmins and a recently identified plant-specific tether family, in viral replication and intercellular transport at a molecular level. The long-term aim is to facilitate targeted breeding for virus resistance, or the development of antiviral inhibitors.

The research will be highly interdisciplinary and provide extensive training in several state-of-the-art technologies:

Interactions of plant viruses with the host proteins and their effects on virus infection will be tested in vivo using confocal and super-resolution microscopy, FRET-FLIM and live-cell RNA imaging. Biochemical, biophysical and structural characterisation of the tethering proteins, including proteoliposome in vitro assays, electron microscopy and X-ray crystallography, will provide a detailed understanding of protein residues crucial for biological function, which will then be modified in the in vivo context to test the effect on virus infection. 

The University of St Andrews is the oldest university in Scotland and consistently ranked as amongst the United Kingdom's top ten universities. The Biomedical Sciences Research Complex is an interdisciplinary research centre where biological, chemical, physical and medical laboratories collaborate under one roof, focusing on host-pathogen interactions. It provides state-of-the-art laboratories and equipment, and a highly international work environment. The James Hutton Institute is one of the world’s leading centers for research of molecular plant-pathogen interactions, including viral, bacterial, oomycete, fungal and insect labs. It provides state-of-the-art containment glass houses and plant imaging facilities. Research at JHI covers the entire spectrum of plant science from basic level all the way to field trials and commercialisation. Both institutions provide international, highly stimulating and interactive environments, and free access to career planning and transferable skills programmes. Opportunities to engage in research translation or outreach are also likely to emerge during the project.

Prospective candidates are highly encouraged to contact Dr Tilsner or Dr Liu.

References:

[1] Barajas et al. (2014) PLoS Pathog 10: e1004388. doi:10.1371/journal.ppat.1004388

[2] Levy et al. (2015) Curr Biol 25: 1-8. doi:10.1016/j.cub.2015.06.015

[3] Perez-Sancho, Tilsner et al. (2016) Trends Cell Biol 26: 705-717

Other: