RNAi workflows for crop protection by silencing virulence genes of fungi and oomycetes with antisense oligonucleotides (ASOs): Chemical modifications and conjugation to nanoparticles for enhancing ASOs silencing potential and delivery

Major losses in crop production are caused by fungi and oomycetes. Traditional disease control involves either fungicide applications or via breeding of new plant varieties introgressed with resistance genes, or insertion of these genes in transgenic plants. However, the downside of such techniques is the negative impact to the environment, disease control evasion due to fungicide resistance build-up, the overcoming of monogenic resistance and the prohibition to farm transgenic plants in the EU. To overcome these limitations, alternative approaches are emerging, exploiting RNA interference (RNAi) coupled to ectopic application of synthetic short dsRNA to silence pathogen virulence factors or host susceptibility genes. We have shown that short antisense oligodeoxynucleotides (ASOs) can be applied to silence Blumeria graminis genes or the barley susceptibility gene MLO to decrease barley powdery mildew infection by 50% in detached leaves. Although encouraging, ASOs’ silencing efficiency and application to whole plants for delivery into cells must be improved in order that this strategy can be effective in the field for disease control. Thus, this project aims to increase the ASOs silencing potential for crop protection to various pathogens by modifying the chemistry of the ASOs to improve their stability, as well as linking the ASOs to (biodegradable) nanoparticles (NPs) for facilitating translocation into host and pathogen cells.

During this 3 years fully funded PhD studentship you will:
- Interact with a multidisciplinary supervisor team composed of biologists and a chemist from Royal Holloway University of London and Imperial College.
- Gain knowledge and expertise in molecular biology microbiology, plant pathology and cell biology and microscopy techniques.
- Become familiar with next generation agricultural practices to protect crops against diseases.
- Develop skills in analytical and synthetic chemistry as you will design chemically modified ASOs to increase their resistance to nucleases, thus increasing their life span and enhancing their silencing potential.
- Get familiar with nanotechnology techniques as you will be synthesizing nanoparticles.

We expect the candidate to have a BSc (upper second class), but in addition with an MRes/ MSc in either biological sciences, biochemistry or chemistry, with good background/ exposure (a plus) or attitude (a must) for the other disciplines. The candidate should also demonstrate plenty of experience in working in a lab environment. Previous practical experience in lab environment set-up, in either plant biology, microbiology or synthetic chemistry will be a great advantage.

This PhD project will be supervised jointly by:
1. Dr Laurence V. Bindschedler, Department of Biological Sciences, Royal Holloway University of London
2. Prof. Alan C. Spivey, Chemistry, Molecular Sciences Research Hub (MSRH), Imperial College London

Applicants are invited to contact supervisor(s) by email ahead of submitting their application. Further information about applying for a postgraduate course at Royal Holloway can be found here:
https://www.royalholloway.ac.uk/studying-here/applying/postgraduate/how-to-apply/

Applications should be submitted online:
https://admissions.royalholloway.ac.uk/#/HEapplicationForm////////1