Peter Sarin

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.

Elizabeth Jakobsen Neilson

“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.

Silvan Scheller

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.

Morten Schmidt

Commonly used painkillers (NSAIDs) are used for the treatment of painful conditions, fever, and inflammation. They are among the most sold medicines in the world but have side effects such as ulcers and increased blood pressure. NSAIDs have now also been linked to heart problems such as heart attack, heart failure, and irregular heartbeat. It is therefore recommended to use NSAIDs with great care in patients with heart disease. This research project will use data from Danish registries to answer important questions on the safety of NSAIDs. It will examine types of NSAIDs not previously looked at and whether warnings from health authorities have influenced doctors’ prescribing of NSAIDs to heart patients. Scientists will also examine whether NSAIDs increase the risk of heart attack in persons with cardiovascular risk factors, such as diabetes, smoking, and obesity. Finally, the project will examine whether NSAID use results in larger heart attacks than in people not using these drugs.

Martin Sillesen

Project description:
Worldwide, an estimated 234 million surgical procedures are performed each year. While most patients proceed to an uneventful recovery, 15% of procedures are complicated by adverse events (AEs), including strokes, heart attacks, blood clots and wound infections. These directly result in an overall 4% risk of death following surgery worldwide. Aside from the impact on the patient, AEs increase health care costs by up to 172%. Accurate risk prediction is thus pivotal for both the patient and society. With this project, we seek to assess the role of genetics and epigenetics in surgical AEs. Furthermore, we will evaluate whether artificial intelligence can assist in both surgical risk prediction as well as the identification of genetic and epigenetic factors of relevance to surgical outcomes. To do this, we have established an international collaboration with Harvard University and the University of Michigan with the hope of collectively identifying novel factors that can reduce surgical AEs.

Karen Louise Thomsen

Non-alcoholic fatty liver disease (NAFLD) is a common form of chronic liver disease. Up to 70% of patients suffer from brain dysfunction with poor outcome and socio-economic impact. NAFLD animals show brain dysfunction and activation of body-wide inflammation and inflammatory cells in the brain. Fat in the liver impairs the normal conversion of nitrogen into urea, causing buildup of the toxin ammonia. A hormone, GLP-1, which is low in NAFLD patients, helps reduce liver fat and brain inflammation. Moreover, abnormal autonomic nervous system signals in NAFLD may add to brain inflammation. We aim to discover if brain dysfunction in NAFLD arises as a consequence of brain inflammation, and if so, what are the potential mechanisms. We will study this: (i) In NAFLD rats and in patients, to ascertain mechanisms using behavioral tests, examinations of liver and brain tissue, and brain imaging, (ii) Experiments targeting therapy to the putative mechanisms (e.g. GLP-1) in rats and as well as in patients.

Olof Idevall-Hagren

Olof Idevall-Hagren says: ”Most cells in the human body are equipped with a primary cilium. This small protrusion function as an antenna that senses changes in the environment and transmit this to the cell body. Defects in primary cilia is the underlying cause of ciliophaties, a group of diseases characterized by diabetes-like symptoms. If there are direct connections between cilia function and diabetes is not known. We have developed tools that enable visualization of activity within primary cilia of insulin-secreting cells and found that these structures are engaged under conditions that modulate insulin secretion. Olof Idevall Hagren will now use these techniques together with methods that suppress or amplify this activity and determine the importance of primary cilia for insulin production and secretion. Our hypothesis is that these antennae coordinate different responses, e.g. insulin secretion, between cells and that defects in cilia function will have a negative impact on these responses and contribute to diabetes.”

Nicolai Wewer Albrechtsen

In this project Nicolai Albrechtsen aim to understand how the human liver ‘works’ when we eat and which biochemical systems within the liver that are impaired in obese individuals and patients with liver diseases. By bridging an advanced clinical setup in humans to state-of-the-art biochemical techniques such as mass-spectrometry and machine learning the goal is to provide the first ‘postprandial human liver atlas’. Evaluating liver profiles of healthy compared to those with liver disease may guide us to a new understanding of how the human liver works and thereby also aid in the identification of new drug targets for liver diseases.

Nicolai Albrechtsen says: “Overload of nutrients and sedentary life predisposes to obesity and liver diseases. Every time we eat, thousands of biochemical processes are activated in order to help our body digest carbohydrates, proteins and fat. The liver is of particular importance for such as it filters and regulates the amount and type of nutrients that reaches our organs”.

Jakob G. Knudsen

Jakob G. Knudsen says: “Type 2 diabetes (T2D) affects more than 400 million people worldwide. Despite great efforts, we have so far been unable to curb the increasing prevalence. While insulin resistance and lack of insulin secretion seems to be the major cause of T2D, it has become clear that the hormone glucagon also plays a critical role. Glucagon is normally secreted to increase plasma glucose levels during fasting but in T2D, glucagon suddenly appears at higher plasma glucose levels and causes hyperglycemia. In this project, Jakob Knudsen will advance single cell resolution microscopy and genetically modify models to determine how α-cell metabolism and glucagon secretion changes in response to metabolic challenges. this way we can explore the mechanisms underlying glucagon secretion in T2D. The understanding of α­-cell metabolism and the basic mechanism of glucagon secretion will not only benefit diabetes research, but also lead to new possible treatments for T2D.”

Morten Frost Nielsen

Morten Frost Nielsen says: “Bone is an active tissue that is remodelled by resorption and formation of bone throughout life. Imbalanced bone remodelling may impair bone and increase fracture risk, e.g. osteoporosis and type 2 diabetes (T2D). Glucagon like peptide-1 (GLP1), a gut-secreted hormone, promotes insulin secretion when food is consumed and improves bone formation in animal studies. The hypothesis of Morten Frost and his group is that GLP1 acts as a nutrient sensor that signals availability of nutrients for bone remodelling. This project aims to determine the effects of GLP1 on bone formation, mass and strength by investigating the effects of treatment with GLP1 and GLP1-like drugs, currently used to treat T2D, on bone cells and bone in healthy individuals and T2D patients with low bone mass. If GLP1 and GLP1-like drugs are beneficial to bone in humans, this investigation will help repurposing GLP1-like drugs as a novel treatment of patients with conditions associated with increased fracture risk including osteoporosis and T2D.”