Wendy Harwood

Prof. Wendy Harwood is Head of the Crop Transformation Group at the John Innes Centre, Norwich where she also manages the BRACT Crop Transformation / Genome Editing Platform. She gained a BSc in Biological Sciences from King’s College, University of London and a PhD in Plant Biotechnology from the John Innes Institute / University of East Anglia. Wendy’s expertise includes genetic modification (GM) technologies in a range of crop species and more recently, the development and application of genome editing technologies in crops.

She lectures at both the Universities of East Anglia and Cambridge; holds an Honorary Readership at the University of East Anglia and a Visiting Professorship for Senior International Scientists from the Chinese Academy of Sciences.

Wendy is active in public engagement, communicating a complex area of science to different audiences through a range of media.

Dr Zhenhua Liu

It has been estimated that plants can produce over 1 million specialized metabolites, but we know less than 0.1 % of their biosynthetic pathways. Creative methods are eminently needed to look under the iceberg of largely untapped biosynthetic pathways. As a post-doc from Anne Osbourn group at John Innes Centre, I am employing multidisciplinary approaches across bioinformatics, genetics, and chemistry, to comprehensively understand how and why plants produce this hallmark of specialized metabolites.

I am currently focusing on plants from the Brassicaceae family and systematically studying the function, evolution and biosynthesis of triterpenes from this family. I am in particular interested in pathways encoded by gene clusters. It holds great potential to mine more and novel biosynthetic pathways efficiently. However, how and why plants have evolved BGCs is still a mystery. We are aiming to gain the first understanding of their assembly, patterns of evolution and common features in a systematic fashion. This knowledge can then be used as a template guiding the research of BGCs in other types of compounds and plant families.         

Figure legend: Multidisciplinary approaches to discover new pathways and novel natural compounds. We are using combination of bioinformatics, genetics and chemistry in attempt to decode and recode the largely untapped plant specialized metabolism

Dr Ingo Appelhagen

I am a molecular biologist, with a background in plant transcription factors, flavonoid biosynthesis, natural colours and metabolic engineering.

In Cathie Martin’s lab at the John Innes Centre, we have recently developed novel suspension cultures from engineered tobacco plants, to obtain stable sources of natural colourants. These cultures can produce exceptionally high levels of red to purple anthocyanin pigments, and allow a scalable constitutive year-around production under controlled conditions.

Intense blue colours are rare in nature and difficult to reproduce in pigment formulations, which is the main reason why almost all blue food colourants are synthetic dyes. Our project aims to investigate the structural properties of anthocyanin preparations that confer strong and stable blue colours and to select for anthocyanins with improved stability as reliable natural colourants. Our goal is to extend our plant cell culture approach to develop the first production platform for blue anthocyanin colourants, to replace synthetic food dyes.

Dr Noam Chayut

I am interested in the interface between applied plant breeding and plant metabolism. In my master’s thesis we used classical breeding of passionfruit with the goal of releasing new varieties, now used by farmers. In my PhD thesis we studied carotenoid metabolism in melons and established a molecular marker now used routinely by melon breeders. More importantly, we suggested a novel non-transgenic path toward pro-vitamin A carotenoid biofortification of food crops. The objective of the current OpenPlant project is to develop pre-breeding lines of beetroot for the production of L-DOPA.  

L-DOPA is used to treat Parkinson’s symptoms; however, the current costs of chemical synthesis make it unavailable for deprived populations worldwide. In addition, there is a growing demand for ‘natural’ or plant sourced pharmaceutical substances in the first world. L- DOPA, a product of tyrosine hydroxylation, is an intermediate metabolite in biosynthesis of violet and yellow betalain pigments, in Beta vulgaris (table beet). L-DOPA natural steady state levels are very low, usually undetectable. We intend to block the turnover of L-Dopa in beetroot to allow its accumulation to levels that could enable low-tech accessible production in a plant system.

Current data indicate two betalain metabolic genes that, if repressed, may boost L-Dopa accumulation. Therefore, we aim to inhibit the activity of L-DOPA-dioxygenase, and L-DOPA-cyclase in beetroot. Currently, as proof of concept, we silence both genes in hairy roots system. We adopted three complementary strategies to meet the overarching objective of L-DOPA production in beet: a) Classical genetics; b) targeted genetic mutagenesis; and c) random mutagenesis. Yellow beet, mutated in L-DOPA-cyclase exists and can be crossed with “blotchy” red beet, which probably has lower L-DOPA-dioxygenase activity. Impairing L-DOPA-dioxygenase activity in yellow beet is carried out by both the targeted mutagenesis technology CRISPR/Cas9 and the random, yet more assured, EMS mutagenesis approach.

Dr Aytug Tuncel

I am applying the genome editing tools to generate novel, commercially or nutritionally valuable glucans in model crop species. The primary objective of my OpenPlant project is to generate potatoes that contain digestion-resistant starches with two major nutritional benefits: reduced calorie intake from consumption of chips, crisps and other potato-based foods and increased supply of complex carbohydrates to the microbiota of the lower gut that reduces risk of several diseases including colorectal cancer and type II diabetes.

More specifically, the project involves knocking out the gene(s) of starch branching enzymes I and/or II using crispr-CAS9 method thereby increasing the ratio of amylose to amylopectin (linear to branched starch chains) in tubers without significantly compromising the starch yield. The engineered starch will be less accessible to starch degrading enzymes, thus more resistant to digestion.

Dr Benjamin Lichman

Plants are incredible chemical factories, capable of producing a host of complex molecules that synthetic chemists struggle to produce. These compounds are produced by plants to interact with their environment, but they also have great significance for humans, as we use them for fragrances, agrichemicals and medicines. My general research interests are understanding how plants produce these valuable compounds, and how these pathways have evolved. This knowledge can then be used to produce natural products and novel chemicals in microbial or plant based platforms.

I am currently working with catnip and catmint (Nepeta cataria and N. mussinii), plants famous for their intoxicating effect on cats. The origin of this activity is the nepetalactones, a group of volatile compounds from the iridoid family of natural products. Along with their role as feline attractants, nepetalactones have also been reported to have both insect pheromone and insect repellent properties, in some cases having activities superior to DEET. The biosynthetic origin of these compounds is currently unknown. We have been using transcriptomics and proteomics to discover enzymes in the Nepeta nepetalactone biosynthesis pathway.

This work is being performed in the context of a wider chemical and genetic investigation into the mint family (Lamiaceae), a large plant family of economic importance in which Nepeta resides. I am working closely with the Mint Genome Project (funded by the NSF) to understand the evolution and regulation of natural product biosynthesis across the entire plant family. By placing newly discovered Nepeta enzymes in a detailed phylogenetic context we hope to understand the evolutionary origin of nepetalactone biosynthesis in Nepeta, and ultimately use it as a case-study for natural product evolution.

I am currently undertaking training in molecular evolution and phylogenetics with the aim of taking the principles of evolution into synthetic biology. I hope that this will reveal new methods of optimising and editing synthetic biology systems and devices.

Figure 1. Nepetalactone biosynthesis pathway in Nepeta. We are attempting to discover the enzymes that catalyse the formation of all different nepetalactone isomers. We are also attempting to understand how these enzymes have evolved. In the background is Nepeta mussinii.

Dr Eva Thuenemann

Plants can be used as a production platform for high-value products such as vaccines, enzymes and metabolites, thereby providing a potentially fast and cost-effective alternative to other cell culture techniques. Developed within the Lomonossoff group, HyperTrans (HT) is a technology for rapid, high-level transient expression of proteins in plants. One key application of HT in the Lomonossoff group has been the production of virus-like particles for use as vaccines, scaffolds for nanotechnology and in fundamental research of virus assembly.

Virus-like particles (VLPs) consist of viral structural proteins which assemble into a particle resembling the virus but devoid of the viral genome and therefore unable to replicate. Different VLPs consisting of multiple copies of one, two or four different structural proteins have been successfully produced using the HT system and shown to be morphologically and immunologically representative of the virus. In recent years, a number of emerging diseases have been caused by enveloped viruses such as Zika virus and Chikungunya virus. Such complex virus structures can make the development of efficient vaccines and diagnostic reagents difficult and costly. In my OpenPlant project, we are working on developing strategies for the production of enveloped VLPs in plants. I am also working on modifying a large non-enveloped VLP to allow accommodation of cargo proteins on the inside of the particle.

In addition to my research project, I was involved in the planning stages for the new John Innes Centre spin-out, Leaf Systems International Ltd, which opened on the Norwich Research Park in January 2017 and will enable translation of research to indsutry through scale-up of plant-based production of proteins and metabolites.

I have also participated in various outreach activities, such as a TV interview for regional news, the Great British Bioscience Festival, JIC’s Speed Science event as well as a work experience day for school children, amongst others.

Dr Michael Stephenson

Twitter

I am a chemist, with a background in natural product total synthesis, medicinal chemistry, and pharmacy. In the Osbourn group we are interested in plant secondary metabolites, and this places us at the very interface between biology and chemistry. I bring expertise in small organic molecule extraction, purification, and structural characterisation. This strengthens the group’s ability to functionally characterise biosynthetic enzymes; something which is important for many areas of research within the Osbourn lab. As such, I am involved in a number of different projects.

My main focus is on the application of transient expression in Nicotiana benthamiana towards the preparative production of high value triterpenes. I have been heavily involved in platform and method development, improving both the efficiency and scalability of procedures used within the group. I have also demonstrated the preparative utility of this platform by producing triterpenes on the gram scale.

As a medicinal chemist I am interested in applying these techniques to engineer chemical diversity, and to explore the structure activity relationships of bioactive triterpenes. I have been involved in isolating and characterising several novel triterpenes structures arising from co-expression of ‘un-natural’ combinations of biosynthetic enzymes. In addition, I have solved the structure of a number of novel and usual triterpene scaffolds, produced by oxidosqualene cyclases under investigation within the group. It would seem that despite the huge number of unique triterpene scaffolds already reported from many decades of natural product isolation, there is still a wealth of novel chemistry to be discovered, and that its discovery can be accelerated by utilising synergy between bioinformatives, synthetic biology, and chemistry.

In addition to my research, I also take a keen interest in public engagement. I have been involved in several outreach events where we attempt to present concepts in synthetic biology and chemistry in an assessable and ‘hands on’ way.    

Dr Hans-Wilhelm Nützmann

Plants produce a wide variety of specialised metabolites. These molecules play key roles in the interaction of plants with their biotic and abiotic environment. In addition to their ecological functions, plant-derived specialised metabolites are major sources of pharmaceuticals and other high-value compounds.

Recently, it was discovered that the genes for the biosynthesis of several major classes of these compounds are physically co-localised in so called ‘gene clusters’ in plant genomes. Such clustering of non-homologous genes contrasts the expected arrangement of genes in eukaryotic genomes. The co-localisation of functionally-related genes enables the formation of fundamentally different mechanisms of gene regulation in comparison to the control of dispersed genes. The purpose of this project is to improve our understanding of the transcriptional control of plant metabolic gene clusters. The focus within OpenPlant will be on chromatin related regulatory processes that govern the expression of gene clusters. By chromatin immunoprecipitation, chromosome conformation analyses and genome engineering we aim to characterise the chromatin environment at gene clusters and its impact on cluster regulation. The findings of this project will open up new opportunities for the discovery and engineering of metabolic pathways using genetic and chemical approaches. They will also underpin synthetic biology-based approaches aimed at refactoring of plant metabolic gene clusters and the development of synthetic traits.