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May 9, 2019

The Novo Nordisk Foundation awards DKK 99 million to excellent research leaders within biotechnology-based synthesis and production research

The Novo Nordisk Foundation has awarded grants of nearly DKK 10 million each to 10 individual scientists in the Nordic countries. The grants are for research within biotechnology-based synthesis and production and are part of the Foundation’s Research Leader Programme, which supports ambitious, original research projects and the continuing development of top researchers.

As part of a sustainable future, fuels and chemical building-blocks need to be produced from non-fossil resources. Can microbes be engineered to efficiently produce the clean fuel and feedstock ethane from unwanted CO2 and renewable hydrogen?

Plants dynamically interact with the environment through a remarkable diversity of chemical compounds. How do enzyme complexes assemble in plants to rapidly produce these chemicals, and can knowledge of these processes be used to optimize bioproduction in microorganisms?

Human population growth is driving a rise in cattle production for food, which increases the need for more sustainable practices. Can comprehensive understanding of how cattle digest their feed enable the development of feeds and processes that optimize nutrition and reduce the emission of greenhouse gases?

These are major questions for three of the 10 ambitious research projects that are receiving grants of close to DKK 10 million each from the Novo Nordisk Foundation. The grants fund excellent and ambitious biotechnology research projects aimed at generating products in improved and more sustainable ways.

The 5-year grants aim to give the researchers the opportunity to pursue substantial projects through a targeted and long-term grant that ensures focus and continuity in their research.

The grants target research leaders at different stages of their careers, and grants were awarded in each of the following categories:

  • Emerging Investigators. Beginning independent researchers to establish their own research groups or strengthen their recently started groups.
  • Ascending Investigators. Associate professor–level investigators capable of leading larger and more challenging studies.
  • Distinguished Investigators. Professor-level investigators with demonstrated ability to address major research questions.

The grants are awarded in open competition based on the applications submitted. The Foundation’s Committee on Biotechnology-based Synthesis and Production Research assessed all 52 applications received from applicants in the Nordic countries.

The 10 grants were awarded as part of the Foundation’s Research Leader Programme. The Programme supports talented research leaders at all stages of their careers and aims to support the continuing development of top researchers. The Foundation recently announced that it has awarded a total of DKK 413 million to 44 research leaders under the Programme. Read the news article here

Grants under the Programme are awarded within four scientific fields: endocrinology and metabolic research; biotechnology-based synthesis and production research; clinical and translational research; and bioscience and basic biomedical research.

The 2019 grant recipients within biotechnology-based synthesis and production research are:

Emerging Investigators

Silvan Scheller, PhD, Assistant Professor

Department of Bioproducts and Biosystems, Aalto University

Grant amount: DKK 9,994,366

Project title: Microbial generation of ethane from carbon dioxide and hydrogen (ETHANOGENESIS)

Project description: ETHANOGENESIS is a microbiological process to synthesize ethane sustainably from CO2 and hydrogen. Ethane can be liquefied at room temperature and utilized as a renewable ship fuel, for energy storage, or as a chemical feedstock. My lead research objective is to change the primary metabolism of methanogens to produce ethane instead of methane. Ethane is formed via acetyl-coenzyme A and ethyl-coenzyme M as the intermediates, in a way that allows the microbes sustain life. As a first step, ethane is produced as a secondary metabolite concomitant with methanogenesis. After modifying the way of ATP generation, methanogenesis will be stopped to obtain ethane as the sole product. Fundamental research is carried out to assess the potential of enzymes thought to be exclusive for C1 substrates towards catalyzing multi-carbon substrates. My research accesses the methanogen-specific pathway of CO2-fixation for the biocatalytic production of multi-carbon fuels and chemicals from unwanted CO2.

 

Elizabeth Jakobsen Neilson, PhD, Assistant Professor

Department of Plant and Environmental Sciences, University of Copenhagen

Grant amount: DKK 9,999,950

Project title: LiftOFF! Optimizing plant FMOs for Future production

Project description: “LiftOFF! Optimising Plant FMOs for Future Production” is an innovative and multi-disciplinary project aiming to characterize novel plant FMO enzymes for downstream use in industrial applications. FMOs (flavin-containing monooxygenases) constitute an important class of enzymes present in all kingdoms of life. FMOs modify bioactive molecules by incorporating molecular oxygen. In humans, this action facilitates the metabolism and detoxification of drugs and xenobiotics. By contrast, the role of plant FMOs is largely enigmatic, with only a handful of members characterized to date. This is highly surprising due to their expected involvement in fundamental processes such as hormone metabolism and plant immunity. LiftOFF! aims to characterize this highly valuable class of plant enzymes and identify novel bioactive molecules formed by the action of FMOs. Furthermore, this project will optimize FMOs as biocatalysts for biotechnology, improving enzyme reconstitution, stability and function.

 

Peter Sarin, PhD, Assistant Professor

Faculty of Biological and Environmental Sciences, University of Helsinki

Grant amount: DKK 9,809,463

Project title: Enhanced Production of Heterologous Proteins Following Translational Fine-Tuning by Optimized Post-Transcriptional RNA Modification (ProteRNA)

Project description: 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.

 

Tomas Laursen, PhD, Postdoctoral Fellow

Department of Plant and Environmental Sciences, University of Copenhagen

Grant amount: DKK 9,999,938

Project title: The language of plant metabolic highways

Project description: 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.

Ascending Investigators

Thomas Poulsen, PhD, Associate Professor

Department of Chemistry, Aarhus University

Grant amount: DKK 9,995,548

Project title: Unorthodox protein reactive electrophiles for biotechnology

Project description: 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.

 

Phillip Pope, PhD, Associate Professor

Photo: Håkon Sparre/NMBU

Faculty of Biosciences, Norwegian University of Life Sciences

Grant amount: DKK 9,992,000

Project title: SuPA[cow]: Sustainable production of animals by optimizing the feed-microbiome-host axis

Project description: 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.

 

Sotirios Kampranis, PhD, Associate Professor

Department of Plant and Environmental Sciences, University of Copenhagen

Grant amount: DKK 9,999,722

Project title: Biotechnological production of structurally complex plant high-value compounds

Project description: 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.

Distinguished Investigators

Lisbeth Olsson, PhD, Professor

Photo: Martina Butorac

Department of Biology and Biological Engineering, Chalmers University of Technology

Grant amount: DKK 9,997,540

Project title: Microbial robustness – a key for sustainable and efficient biotechnology-based production

Project description: 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.

 

Birger Lindberg Møller, DSc, Professor

Department of Plant and Environmental Sciences, University of Copenhagen

Grant amount: DKK 9,439,227

Project title: The Black Holes in the Plant Universe

Project description: 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.

 

Morten Petersen, PhD, Professor

Department of Biology, University of Copenhagen

Grant amount: DKK 9,683,189

Project title: Exploiting microbial effector targets to optimize plant protection and crop yield

Project description: 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?

 

About the Novo Nordisk Foundation

The Novo Nordisk Foundation is an independent Danish foundation with corporate interests. It has two objectives: 1) to provide a stable basis for the commercial and research activities of the companies in the Novo Group; and 2) to support scientific, humanitarian and social causes.

The vision of the Foundation is to contribute significantly to research and development that improves the lives of people and the sustainability of society. Since 2010, the Foundation has donated more than DKK 20 billion (€2.7 billion), primarily for research at public institutions and hospitals in Denmark and the other Nordic countries as well as research-based treatment and prevention of diabetes. Read more at www.novonordiskfonden.dk/en

Further Information

John Wittschieben, Senior Scientific Officer, phone +45 3527 6613, jpwi@novo.dk

Christian Mostrup Scheel, Senior Press Officer, phone: +45 3067 4805, cims@novo.dk

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