Rune Hartmann

Rune Hartmann says: Balancing pro-inflammatory and antiviral responses during a viral infection is a key challenge for our immune system and a major determinant of our ability to survive an infection. The pro-inflammatory responses are largely driven by the NFκB signaling pathway but determining the molecular mechanism whereby viral infections induce NFκB signaling and thereby inflammation has proven difficult in mammals. We recently discovered that the STING – NFκB axis represents an evolutionarily conserved antiviral pathway present in all metazoans. In mammals, the NFκB pathway has a dual function and is also required in developmental processes, which makes it difficult to study. In contrast to mammals, flies contain a NFκB transcription factor called Relish, which is required for the immune response, but apparently no function outside immunity. This opens a unique opportunity to use the power of the Drosophila model organism for characterizing the role of the STING – NFκB signaling axis in antiviral immunity and then translate those findings back in the mammalian system. We aim to use the powerful biochemical and genetic tools as well as unbiased screening approaches available in Drosophila to identify key components of the STING – NFκB axis. Our proposed work will allow us to understand how NFκB drives a pro-inflammatory signal and how the resulting inflammation creates significant pathology during viral infection in humans. Knowledge, which may prove critical to develop novel therapeutic strategies for specific targeting of the STING – NFκB signaling axis to lower inflammation in patients.

Rune Hartmann is Professor and Group Leader at the Department of Molecular Biology and Genetics, Aarhus University.

Jakob Nilsson

Jakob Nilsson says: Human health depends on our cells’ ability to respond to changes in the environment and the ability of cells to communicate within and with each other. Such cell signaling and communication depend on a chemical process whereby enzymes add or remove a so-called phosphate group from a protein. Thus, addition and removal of phosphate groups from proteins are fundamental signaling mechanisms that are often deregulated in human disease.  Understanding how the enzymes that add or remove phosphates are regulated will reveal fundamental insight into cell function and will provide a new perspective on human diseases. In this project, we will use new methods we have developed to identify and characterize how the enzymes that remove phosphates are regulated. We will use sophisticated cell biological and biochemical methods to understand how these new regulatory mechanisms impact on cellular function to potentially uncover novel disease-causing mechanisms.

Jakob Nilsson is Professor and Group leader at the Novo Nordisk Foundation Center for Protein Research, University of Copenhagen.

Mette Burmølle

Mette Burmølle says: Like humans, bacteria can be infected by virus. Bacterial viruses are called bacteriophages (phages) and they infect specific bacteria, often resulting in cell death. Bacteria cause many human diseases, which, with the rapidly expanding antibiotic resistance crisis, we are losing the ability to cure. This has severe consequences and calls for alternatives to antibiotics. Phages represent such alternatives, and their therapeutic potential is currently tested and evaluated. However, these tests are commonly conducted in simple model systems with little relevance to the bacterial life in nature and infections. In this project, I will study phage-bacteria interactions in settings resembling the bacterial natural lifestyle, in biofilms. Here, mixed bacterial communities are encased in a protective matrix, which influences phage susceptibility. The results will be foundational for development of efficient strategies using phage therapy as alternatives or supplements to antibiotics.

Mette Burmølle is Associate Professor at the Section of Microbiology, University of Copenhagen

Rune Berg

Rune Berg says: Every day, we elegantly and effortlessly move our bodies. The brain generates the commands to contract muscles and, in this way, orchestrates the motion. But how do our brains do it? It is a fundamental part of our lives, yet we do not understand the roots and the mechanisms of how even seemingly simple movements, like walking and reaching for a cup, are produced. In this research proposal, we will investigate how different brain regions communicate with the spinal cord to produce movement sequences using new techniques. This will provide unique and crucial information to understand the nervous system, and how signals propagate across regions. Understanding the foundation of these neural circuits will not only satisfy our curiosity on how we move, but it may also explain the impact of circuit disruption from stroke or spinal cord injuries. This could introduce a path forward for a new clinical therapy for conditions where the motor circuitry is affected, like spinal cord injury and stroke.

Rune Berg is Associate Professor at the Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen.

Nicholas Taylor

Nicholas Taylor says: Not only humans have viruses that can attack them but also bacteria are under constant attack by viruses, which are known as bacteriophages. In fact, bacteriophages are the most abundant biological units on the planet. Since bacteriophages can kill bacterial cells, they have been used as an alternative to antibiotic therapies to treat bacterial diseases in humans.

It has quite recently been discovered that, like humans, bacteria also have immune systems that protect them against their viruses. How this occurs is however much more poorly understood. I plan to investigate this by looking with very advanced microscopes at these systems and trying to unravel how they work at the molecular level. Furthermore, we will take the first steps to try to make novel applications based on the fundamental mechanisms that we discover, which could ultimately lead to novel application in biomedicine or biotechnology.

Nicholas Taylor is Associate Professor and Group Leader at the Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Denmark.

Andrew Blackford

Andrew Blackford says: DNA is found in every cell in our bodies and encodes the blueprints that make us what we are. Although DNA is relatively stable, there are ways it can become damaged so that bits of it are lost or changed so that it no longer works the way it should. Common sources of DNA damage include ultra-violet rays from the sun and by-products that come from what we eat, drink, or breathe in, such as alcohol and tobacco smoke. In fact, DNA is damaged so often that our cells have evolved to produce proteins that are able to repair it. One set of proteins that helps do this is called the RecQ helicases. We know that RecQ helicases play an important role in our bodies because when they are mutated, this can lead to syndromes associated with increased cancer risk, premature ageing, and a faulty immune system. The aim of this proposal is to investigate how the RecQ family of helicases functions at the molecular level, which is still relatively poorly understood but is very important for human health.

Andrew Blackford is currently Associate Professor and group leader at the MRC Weatherall Institute of Molecular Medicine, University of Oxford, UK. With the grant, he will relocate to the Department of Cellular and Molecular Medicine, University of Copenhagen, where he will be associated with the DNRF Center for Chromosome Stability as Associate Professor and Group Leader.

Rasmus Kock Flygaard

Rasmus Kock Flygaard says: A characteristic feature of life is the need to separate the exterior world from the interior environment of a cell. This is achieved by the use of semi-permeable bilayer membranes. In bacteria and eukaryotic mitochondria, an important and special membrane building block, named cardiolipin, is used. Although mitochondria were once bacterial cells on their own, mitochondria and bacteria use different mechanisms to make cardiolipin. The details of this difference are unknown to us. In this project, I want to reveal this difference on a molecular level, and I will study why important human parasites have retained a bacterial-like system to synthesize cardiolipin. The results of my work will hopefully elucidate why some patients, who cannot make cardiolipin, become very sick. Ultimately, my results will also serve to determine if parasites can be battled by targeting their cardiolipin synthesis machinery.

Rasmus Kock Flygaard is currently employed as a Postdoc at Aarhus University and will establish his independent research group from 1 October 2023.

Gilles Vanwalleghem

Our gut is regulated by the enteric nervous system, and together with the gut microbiome, it constitutes the gut-brain axis. Imbalance in the gut-brain axis can lead to chronic inflammation, impact mental health and lead to a decreased quality of life.

Gilles Vanwalleghem says: This proposal will use a transparent fish to look at the enteric nervous system and inflammation in development. We will compare how the gut develops with or without microbiome in an inflammed state. We will look at how this inflammation could impact the gut and its function. On the other hand, the enteric nervous system can sense bacteria and guide inflammation, and we will develop mutants to better understand how this works. Finally, we will look at how all these factors can influence the social behavior of the fish, and if we can help the fish develop normal behaviors. The results will guide us in how and when we can best intervene on the gut to ensure good gut function and normal neurodevelopment.

Gilles Vanwalleghem moved from University of Queensland to Aarhus University in 2021. He is now employed as a team leader within Danish Research Institute of Translational Neuroscience (DANDRITE) and as Assistant Professor at the Department of Molecular Biology and Genetics, where he will establish his independent research group from September 2023.

Laurits Skov

Laurits Skov says: Our closest evolutionary relatives the Neanderthals and Denisovans are now extinct. However, part of them still lives on through us in our genomes. Most people of non-African descent trace 1-2% of their ancestry to Neanderthals and 0.01-5% to Denisovans, and we can therefore reconstruct the genomes of these extinct archaic humans from our own genomes. This will allow us to answer questions such as: How many archaic humans contributed to our genomes? How many times did we encounter them and how long did we coexist? When did they go extinct? How do their genes affect us today? Are there parts of our genomes that are uniquely human?

I will develop novel computational methods to answer these questions and apply these methods to data from 1.1 million human genomes. This will give us a unique glimpse into the past lives and history of extinct humans and characterize their impact on our genomes.

Laurits Skov is currently a postdoc at University of California (Berkeley). He will relocate to the Bioinformatic Research Center (BIRC) at Aarhus University on 1 April 2024 to establish his independent research group.

Signe Mathiasen

In Denmark, the burden of psychiatric and mental disorders has been predicted to constitute 25% of the public health problems and the consequences of mental illnesses is both highly afflictive to individuals and of great cost to society.

Signe Mathiasen explains: In this project, we study a new and novel receptor target in mental health, the adhesion G protein-coupled receptor latrophilin 3 (ADGRL3), which is implicated in attention-deficit/hyperactivity disorder (ADHD) and other psychiatric disorders that involve dopamine dysfunction, such as schizophrenia. Specifically, the goal is to map the dynamic localization of ADGRL3 receptors in the cell membrane and to correlate its movements to interaction partners out-side and in-side the cell. This will enable us to determine how, where and when ADGRL3 function as a signaling unit with its key synaptic interaction partners. Such basic understanding can help uncover the potential of ADGRL3 as a novel drug target for new and improved pharmacotherapies in e.g. ADHD.

Signe Mathiasen moved back to Denmark in 2020, after working as a scientist for six years at Columbia University. She is currently employed at the Department of Biomedical Sciences, University of Copenhagen, where she will establish her independent research group with the NNF Emerging Investigator grant starting 1 April 2024.