A CRISPR approach to improving natural product synthesis with plant biotechnology

The production of medicinal proteins in tobacco plants is an established platform, but heterologous production of small chemical compounds known as secondary metabolites is an emerging field. Plant secondary metabolites have provided some of the most important medications in our arsenal against disease such as paclitaxel, opioids, and the frontline antimalarial treatment: artemisinin. However, plants which naturally produce these medicines are not amenable to large-scale agriculture. Hence the developing field of engineering tobacco, which is the second-highest biomass crop, grown globally, and can be easily genetically altered, to produce these important medicines. Due to its medical importance, both as an antimalarial and also as a potential cancer chemotherapy and COVID19 treatment, several attempts have been made to produce artemisinin in tobacco. However, while these attempts did produce artemisinin or the penultimate precursor, they were thwarted by poor yields. The main reason for this has been proposed to be glycosylation – the process by which secondary metabolites are fused with a sugar molecule through enzymatic processes.

The project proposed herein will take an iterative approach to investigate the artemisinin biosynthetic pathway as a model for heterologous secondary metabolite production. We will investigate where the rate-limiting step(s) is in the pathway, genetically engineer the plant to prevent glycosylation, and produce secondary metabolites. Techniques routinely performed will include:

Molecular biology including PCR, CRISPR, and cloning

Biochemical techniques such as HP-TLC

Cell biology, including cell culture and IC₅₀s

Entry requirements and how to apply

Candidates should have a minimum classification of 2.1 in their bachelor’s degree or equivalent and preferably a Masters degree. Applicants whose secondary level education has not been conducted in the medium of English should also demonstrate evidence of appropriate English language proficiency normally defined as IELTS: 6.5 (overall score with not less than 6.0 in any of the individual elements).

You can read more about what should be in a PhD research proposal here:

https://www.westminster.ac.uk/study/postgraduate/research-degrees/entry-requirements/how-to-write-your-research-proposal

You can read more about our entry requirements here:

http://westminster.ac.uk/study/postgraduate/research-degrees/entry-requirements

Applications should be submitted by Friday 16^th May 2025. Interviews will take place in June.

It is essential you include the code of the project you are applying for in your personal statement i.e. “SLS SF1”.