Morten Petersen

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?

Birger Lindberg Møller

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.

Lisbeth Olsson

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

Lars Søndergaard

During the last decade, treatment of aortic valve stenosis using transcatheter aortic valve implantation (TAVI) has been established and is now proven to be at least as good as the traditional surgical treatment in elderly patients and in patients with other diseases besides their cardiac problem. This study, the NOTION-4 trial, is a Nordic collaboration to test the optimal blood thinning treatment strategy after patients have received a transcatheter heart valve. Two medical regimens will be tested in patients with stable heart rhythm (sinus rhythm). In patients with unstable rhythm (atrial fibrillation), who require stronger blood thinning, the effectiveness of implantation of a plug in the heart chamber where most blood clots origin, is tested, with the purpose of reducing the amount of blood thinning and thereby reduce the risk of bleedings and other important side effects. The trial uses the technique of randomization – the preferred scientific technique when testing different treatment strategies.

Anja Pinborg

More than 3000 children or 5–6% of the Danish birth cohort are born annually after in-vitro fertilization (IVF) techniques. Frozen embryo transfer (FET) has been increasingly used to avoid twin gestations as a single embryo can be transferred and the surplus embryos frozen. Vitrification, an ultra-fast freezing method, has improved the survival of frozen embryos from < 50% with the slow-freeze method to > 95%. However, singletons born after FET have a higher risk of being born larger than others at same age, which may increase their risk of diabetes and cardiovascular disease. In this project we will examine BMI, metabolism, endocrine and cardiovascular parameters and their genome control mechanisms (epigenetic modification) in 600 singletons aged 6 to 8-years born after A. FET; B. Fresh embryo transfer; and C. Natural conception. This study is the first of its kind worldwide and will have wide implications for the IVF treatment strategies in the future (www.HiCART.dk).

Anders Perner

The sickest patients in hospitals are cared for in the intensive care unit (ICU). In the ICU, most patients are treated with advanced life-support. Despite this, many patients die, and the survivors and relatives struggle with reduced quality of life for years. It is therefore a paradox, that many of the treatments we give to ICU patients, have not been tested in such patients. We give these treatments based on tradition and tests in less sick patients. Worryingly, we recently found that some treatments harmed the ICU patients. Therefore, we conduct clinical trials to directly improve the treatment of ICU patients. As a result, more patients survive and we give patients less medicine and less blood and the overall cost has been reduced. With the IMPROVE-ICU program, we will further improve the clinical trials we conduct. This will improve the treatment of blood poisoning, unstable heart rhythm, fluid and blood loss and the way we use blood sampling to the benefit of patients, relatives and society.

Marja Jäättelä

With this project, Marja Jäättelä and her group will map how different types of dietary fats are used as building blocks in cells and how they affect their functions. The ultimate aim of the project is to enable a better use of diets in the prevention and treatment of various diseases.

Marja Jäättelä says: “We know today that there are different types of fats in our food and that they have both good and harmful effects on our health. But we do not know so much about how these fats distribute in our body or how they affect different tissues. Therefore, we wish to investigate how different types of fats in food are used in the body. For this purpose, we will feed mice with excess of specific dietary fatty acids and then determine the fat composition of cellular membranes and other lipid-containing molecules in various tissues.”

Pål Njølstad

Pål Njølstad says: “Childhood diabetes infers a great burden on affected children and their parents due to complicated and painful treatment, and the development of diabetes-associated complications. In many clinics around the world, children with diabetes are generally thought to suffer from type 1 diabetes, not further investigated, and treated with insulin for life. Recent advances in genetics indicate that many children with apparent type 1 diabetes may suffer from a genetic subtype of diabetes which may mean oral drugs are better than insulin injections.
In this study we will use new genetic tools to identify rare genetic variants in childhood diabetes, to shed light on their functional role in cell models, and to use this information for improved treatment of children with diabetes. Children carrying mutations in genes involved in insulin secretion will be tested whether they can switch treatment from insulin to sulfonylurea tablets, thus providing safe, painless, and personalized treatment.”

Sara Linse

Sara Linse says: “Type-2 diabetes affects over 400 million people world-wide and is linked to aberrant behavior of the hormone IAPP. IAPP is produced, stored and released together with insulin, which is needed for our sugar metabolism. In most cases of type-2 diabetes, IAPP is found in aggregated form. This causes death of the insulin-producing cells. Current efforts to develop inhibitors against IAPP aggregation are spent without knowledge of the underlying mechanism. This is where this project comes in. We will first solve the mechanism in term of which steps happen and which of these steps cause death of insulin-producing cells. Inhibitor design will then target exactly these steps to limit cell death. This is important as targeting the wrong steps can even lead to increased cell death. We will optimize all parts of the experiments needed to find the mechanism in the relevant biological fluid, and the action of each potential inhibitor under conditions relevant to the situation in the human body.”

Claes Ohlsson

Claes Ohlsson says: “With increasing age of the population, we are facing a substantial increase in bone fragility fractures, which account for considerable disease burden and costs. Therefore we aim to improve the prevention, diagnosis and treatment of osteoporosis and related fractures. We will identify human genetic signals for a variety of specific fracture-related phenotypes and translate these to novel mechanisms regulating fracture risk. The clinical usefulness of the most promising genetic markers will be evaluated in the fracture risk prediction tool FRAX® that, according to national guidelines in Sweden and many other countries, should be used to aid in fracture risk prediction and thereby in the selection of individuals who would benefit most from osteoporosis treatment. Our vision is to develop fracture type-specific diagnostic tools and treatments facilitating a more personalized anti-fracture therapy.”