Marco Donia

Marco Donia says: “Immunotherapy works by re-activating the body’s immune system to recognize and eliminate cancer. Some patients with advanced cancers, including melanoma, lung, and renal cancer, can be cured by current immunotherapies. However, most patients whose cancers initially regress after immunotherapy become resistant and grow back again. The determinants leading to this “acquired resistance to immunotherapy (ARI)” are unknown. Consequently, there is no curative treatment for patients who develop ARI. This project will pinpoint the genes and molecules responsible for ARI. Based on clinical data, we will generate complex high-throughput preclinical models to reproduce and study the molecular determinants behind immune evasion. These models will then be used to test therapeutic strategies against resistant cancers. These works will pave the way for new potential treatments for patients with ARI.”

Marco Donia is Staff Oncologist at the Department of Oncology, National Center for Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital (Herlev and Gentofte), and Associate Professor, Department of Clinical Medicine, University of Copenhagen, since 2017.

Anne Skakkebæk

Anne Skakkebæk says: “Sex chromosome aneuploidies (SCAs) are conditions where females or males have an abnormal number of sex chromosomes, like Turner syndrome (45,X) and Klinefelter syndrome (47,XXY). Patients with SCAs suffers from a range of diseases (congenital malformations, infertility, diabetes, cardiovascular diseases, psychiatric diseases). The fetal period and early childhood are critical periods with complex mechanisms regulating the activity of our genes being founded. These mechanisms have profound impact on health and disease. Our hypothesis is that altered dosage of sex chromosomes disrupt these mechanisms in the fetus and child with SCA, leading to the increased disease burden thorough out life. We will examine these mechanisms in tissues from aborted fetuses with SCAs, and in tissue samples from children with SCAs and control fetuses and control children. In addition, we will measure health outcome and other clinical measurements of the fetuses and children to answering the fundamental biological question how altered sex chromosome number leads to an increased diseases burden in SCAs.”

Anne Skakkebæk is medical geneticist at the Department of Clinical Genetics, Aarhus University Hospital, and Clinical Associate Professor at Department of Clinical Medicine, Aarhus University, since 2021.

Astrid Juhl Terkelsen

Astrid Juhl Terkelsen says: “Parkinson’s disease (PD) is common, disabling and caused by neuronal death due to neurotoxic deposition of a protein, α-synuclein in the central and peripheral nervous system. Accumulating evidence suggest early involvement and spread of α-synuclein via the peripheral to the central nervous system. We present a model of very early PD confined to the peripheral nerves thus preparing for disease-modifying treatments earlier than hitherto possible before damage to central neural structures. These early PD patients are found by screening neuropathy patients for abnormal blood pressure regulation and for damage to the nerves innervating the heart which is early signs of PD. We will describe the patients in detail by looking at α-synuclein in skin, measure the function of the peripheral nervous system with various sophisticated tests and follows the patients for five years to detect both PD and related diseases. Furthermore, we will build a biobank on blood, skin and spinal fluid to define risk factors for developing PD.”

Astrid Juhl Terkelsen is Consultant at the Department of Neurology, Aarhus University Hospital, neuromuscular division and head of the Autonomic laboratory evaluating, diagnosing and treating high specialized patients with autonomic neuropathies. Astrid Juhl Terkelsen has been Associate Professor at Department of Clinical Medicine at Aarhus University since 2016.

Bo Gregers Winkel

Bo Gregers Winkel says: “Each year in Denmark, 5,000 individuals suffer a cardiac arrest (CA). Presently up to 16% of the individuals survive. This project aims to identify causes and risk factors of ventricular arrhythmias, improve treatment, and strengthen rehabilitation of CA survivors. Three large randomized trials will be conducted: 1) the RIME-IVF trial will investigate the effect of adding medical treatment in unexplained cardiac arrest survivors, 2) the ATP trial will examine how implantable cardioverter defibrillators best treat ventricular arrhythmias, 3) the ROCK trial will investigate how to best rehabilitate CA survivors, to effectively return to their work and life after the CA. Additionally, the project collects data on all SCD cases and CA survivors to increase knowledge of the causes of SCD, to construct a risk prediction model to optimize treatment, and to offer preventive care to the families.”

Bo Gregers Winkel is consultant cardiologist in non-invasive electrophysiology at Department of Cardiology, Rigshospitalet – specialized in inherited cardiac diseases and cardiac arrest survivors.

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.

Petra Sipilä

Androgens are required for the male reproductive tissues. However, in many target tissues the regulation of cell type specific responses to androgen action remain poorly understood. Dramatically declined male fertility with low sperm counts and poor semen quality underlines the compelling need of understanding the process of fine-tuning the androgen response in the epididymis where sperm mature. Androgens signal in cells through androgen receptor. Our studies are aimed at revealing novel mechanisms regulating androgen receptor activity in the epididymis. We will focus on other transcription factors working with androgen receptor, epigenetic marks and post-translational modifications of androgen receptor. With this proposal, we will improve our understanding of the mechanisms of androgen signaling in the epididymis that are relevant for male fertility, in order to uncover targets for novel infertility biomarkers and non-hormonal contraceptive modalities.

Christian Benedict

Through advanced sleep-tracking technologies and continuous glucose monitoring applied under free-living conditions, my project will help decipher to which extent broken sleep, an umbrella term describing sleep patterns hallmarked by short sleep duration, low-quality sleep, late bedtime, and irregular sleep timing, impacts daily blood glucose profiles in 240 individuals with overweight or obesity. My project will also be the first to study whether day-to-day variations in the length and depth of the most restorative sleep stage, slow-wave sleep, matter for daytime blood glucose control in people with unhealthy weight, as previously demonstrated in small experiments involving metabolically healthy normal-weight adults. We also hypothesize that blood glucose surges occurring near sleep onset, indicative of late eating, alter the restorative power of subsequent nighttime sleep, with possible negative implications for brain health. Understanding the interaction between sleep, glucose control, and brain health in this population at risk for type 2 diabetes may inform the development of interventions to improve sleep and blood glucose management and potentially benefit brain health.