Plant Virus-Based Multi-Enzyme Catalytic Nanoparticles

Plant viruses are natural, self-assembling nanoparticles. Because they can be produced cheaply and safely in large quantities, they have become widely used as scaffolds for nanotechnology. Novel functionalities can be immobilized and displayed on viral particle surfaces. In most systems, this is done by chemical coupling ex-vivo, which requires both the virus particles and the desired functionality to be produced and purified separately first. By contrast, the filamentous virus, Potato virus X (PVX), can be engineered to display full proteins on its surface in vivo by genetically fusing them to the capsid protein (CP)(‘overcoat’ virus) - so far up to 46 kDa, but an upper limit has not been systematically tested. The important benefit of this approach is that the surface-presented proteins do not have to be purified separately, but are pre-coupled to the virus particles. This makes PVX ideally suited as a scaffold for the immobilization of enzymes, an important approach to improve their lifetime and retention in industrial biocatalysis. PVX ‘overcoat’ technology has been used to immobilize a commercially important lipase [1], but so far, a systematic development of this highly promising nanotechnology is lacking. In particular, due to the principle of superinfection exclusion, which prevents mixed infections with PVX derivatives with different CP fusions, only a single enzyme can be attached to PVX virions. This project will overcome this limitation and assemble multiple enzyme pathways on PVX nanoparticles.

In collaboration with Dr Rebecca Goss, a bio-organic chemist, the PhD student will assemble in the first instance a 2-enzyme pathway that is of immediate industrial interest, and test enzymatic activity of the nanoparticles. Building on this proof-of-principle, the student will then develop a “plug-and-play” vector system allowing the assembly of more complex biochemical pathways.

The project is highly interdisciplinary and will provide extensive training in molecular biology (including current restriction-free cloning systems), development of virus-based vectors and working in containment facilities, as well as in electron and confocal microscopy. The student will also be trained in bio-organic chemistry and enzyme assays relevant to the project, and have the opportunity for direct interactions with industry partners. Training in presenting data and writing of scientific manuscripts will be provided and the student will be encouraged to participate in the protection and exploitation of IP arising from the project.

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. PhD students have free access to career and transferable skills training.
Prospective candidates are highly encouraged to contact Dr Tilsner at [Email Address Removed] or Dr Goss at [Email Address Removed]