Plant pathogens deliver effector proteins into plant host cells to increase infectivity by modifying or removing protective host proteins. Plants detect effector proteins via NLR immune receptors which monitor host effector targets. In response to effector target tampering, NLRs potentiate immunity. The guard hypothesis thus proposes that NLRs ‘guard’ host ‘guardees’. A corollary to this is that autoimmunity in plants may be due to inappropriate NLR activation and not caused by mutations in negative regulators of immunity as described in many highly cited research papers.
We therefore developed a novel, rapid suppressor screen based on specific Dominant Negative (DN-NLR) mutations in a conserved NLR domain. This screen confirmed that autoimmunity in many mutants require NLRs. Since we can now remove the effects of the triggered NLR guard(s), we can properly ask three important questions:
1 – What are the true functions of the guardee proteins?
2 – Why are they guarded?
3 – How can we exploit them to increase plant production?
We are currently moving rapidly into “The Plantroprocene Era” where fossil fuels must be replaced with bioproduction. Green photosynthetic organisms play a vital role in this transition as providers of both food, biomaterials and energy as well as essential medicines, nutraceuticals, condiments and colorants. These molecules are typically produced in very small amounts in the plants, making extraction difficult and harvest in nature unsustainable. However, some plant species like the vanilla orchid and sorghum possess an intriguing ability to produce and store some of these rare and sparingly soluble substances in liquid form at seemingly impossibly high concentrations in bio-condensates – “Black Holes”. This research initiative aims to elucidate the unknown mechanisms in the plant cell that orchestrate the establishment of such “Black Holes” and define new options for future plant-based production of high-value natural products. The knowledge gained will bring our understanding of molecular mechanisms determining plant plasticity to an entirely new level and guide development of crops with increased robustness to climate change.
One direction to mitigate the climate change is the transformation from a fossil-based economy towards a biobased economy. Here, biomass is employed as raw material and biochemical conversion plays a central role in the production of the key chemicals needed in society. A prerequisite is the availability of robust microorganisms to be used in the conversion. Microbial robustness refers to the cells ability to perform under challenging conditions that prevail in industrial processes. Here, using yeast as a the microbial platform, both natural yeast diversity and laboratory evolved strains that exhibit different fitness will be a starting point for identifying molecular traits behind microbial robustness. A molecular understanding of microbial robustness will be achieved in the research program and this insight will guide the design of the urgently needed biocatalysts. Molecular markers that can monitor the cellular status will also be identified – an important tool to follow fermentations.
Photo: Martina Butorac
Plant natural products are complex chemical compounds with important applications as pharmaceuticals, flavours, fragrances and colorants. Production of plant natural products in engineered microorganisms is an economic and sustainable alternative to inefficient chemical synthesis and limited natural resources. However, many valuable plant natural products, such as those used as pharmaceuticals, have very complex structures and their biosynthesis involves a large number of steps, hindering their biotechnological production. Our work aims to develop the tools and methods to efficiently produce complex plant natural products in the yeast Saccharomyces cerevisiae. Using the potent anticancer agent taxol as a prototype, we will develop continuous in vivo mutagenesis-based evolution, dedicated biosensors, optogenetically-controlled compartmentalization, and bioassay-coupled combinatorial biosynthesis to establish a blueprint for the successful biotechnological production of structurally complex plant natural products.
Human population growth is driving a rise in cattle production for food, which necessitates more efficient and sustainable practices. One promising route to achieve this, is to unravel the connection between the feed cows eat, their bodily function and the microbes in their gut, not only to optimize nutrition but also to reduce the emission of greenhouse gases (methane). Our new strategy to collectively study the animal, its diet and all its microbes as one unit (the holobiont), is known as holo-omics. This strategy, enabled by recent biotechnological developments, can improve our understanding of how animals digest their feed and sustain their growth. This project combines novel methane-inhibiting feed ingredients, animal experiments and holo-omics to jointly analyze cows, their feed and their microbes. The outcome will be optimization of feeding strategies tailored to specific types of cows, to ultimately improve their growth and production whilst reducing their carbon footprint.
Photo: Håkon Sparre/NMBU.
Chemistry is at the heart of modern biotechnology. Of particular relevance is the development of chemical processes or reagents which enable production of biological drugs – such as antibodies or peptide hormones – with enhanced or straight-out novel properties. Chemical reactivity can also be favorably embedded within small molecule drugs to improve both specificity and efficacy. In this project, we will focus broadly on the development and application of new types of chemically reactive groups that are compatible with use in biological systems and which can enable construction of novel types of bioconjugates. We will also integrate the efficient synthesis of high-complexity reactive compounds with detailed mapping of both direct proteomic targets and overall bioactivity profiles – the latter using an image-based approach. The goal is to identify precisely those special molecules with unprecedented modes-of-action which can be starting points for further development.
Plants are the supreme chemists that hold the key to ensure a future sustainable supply of medicine, food and energy. Plants sense and communicate with their environment using an elaborate “language” composed of a remarkable diversity of bioactive compounds. Specific production of such compounds involves on-demand assembly of enzyme complexes, metabolons, which facilitate the formation of metabolic highways. “The language of plant metabolic highways” focuses on elucidating how plants orchestrate the formation of metabolons. Our recently developed method for isolation of intact metabolons enables unprecedented snapshot analyses of their composition. This, in combination with single molecule microscopy will provide a unique insight into the dynamic metabolic machinery of plants. This has the potential to fundamentally change our view of how plants produce the remarkable diversity of bioactive compounds and bridges the knowledge-gap currently impeding optimized bio-production in microorganisms.
To efficiently produce their own proteins, cells have evolved a seamless interplay between the nucleic acid and protein components of the translation machinery. In translation, the demands posed by the messenger code need to be matched by the supply of adapter molecules (tRNAs), which carry the amino acid building blocks required for the nascent protein chain to be formed by the ribosome. This careful balance is often perturbed in bioproduction systems, as the proteins-of-interest commonly originate from other organisms with inherently different synthesis requirements. To overcome this challenge, ProteRNA will optimize the small chemical groups that are naturally present on tRNAs, changing their abundance and identity to improve the efficiency of synthesis and to increase the yield of functional proteins. ProteRNA will establish this proof-of-concept and generate a detailed and applied understanding of protein synthesis modulation by adjusting tRNA modification.