The Novo Nordisk Foundation has awarded Investigator grants for DKK 118 million for research within bioscience and basic biomedicine as part of its Research Leader Programme. The Programme aims to support ambitious, original research projects and the continuing development of top researchers.
Understanding how viruses evolve and develop resistance to antiviral drugs to help combat future infections. Developing advanced algorithms and computational stimulation of the neural signals in the brain to help understand the perception of pain and ultimately help people living with common chronic pain conditions. And creating new knowledge about central messenger-RNA–regulating mechanisms in plants to not only help us understand how plants grow but maybe tell us something about these central mechanisms in humans as well.
These are the aims of 3 of 12 ambitious fundamental research projects that have just received grants of close to DKK 10 million each from the Novo Nordisk Foundation. The grants awarded are for basic research within biomedicine and bioscience, with the overall aim of understanding the human organism and/or basic mechanisms underlying health and disease.
The grants last 5 years and aim to give the researchers the opportunity to pursue ambitious and relevant projects through a targeted and long-term grant that will ensure focus, continuity and stability in their research.
Four of the 12 grant recipients will relocate to Denmark to set up their independent research groups at various universities across Denmark. All 12 will contribute to educating and inspiring the next generation of researchers.
The grants target research leaders at different stages of their careers, and four grants were awarded in each of the following categories:
- Hallas-Møller Emerging Investigators. Young promising research leaders wanting to establish or are in the process of establishing their own research group and research profile.
- Hallas-Møller Ascending Investigators. Talented, established research leaders at the associate professor level.
- Distinguished Investigators. Professors of high international standing and calibre.
The grants were awarded in open competition following a call for applications. The Foundation’s Committee on Bioscience and Basic Biomedicine assessed all 118 applications received.
The 12 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 just announced that it is has awarded a total of DKK 430 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 grants recipients within bioscience and basic biomedicine are:
Hallas-Møller Emerging Investigators
Joseph Rogers, 32, researcher
Joseph will relocate from Boston, United States, where he is currently working for Vertex Pharmaceuticals to set up his independent research group at the Department of Drug Design and Pharmacology, University of Copenhagen.
Grant amount: DKK 10,000,000
Project title: Massive searches of sequence space to probe diverse protein behaviours
Joseph Roger says: “Proteins are the main molecules in biology, and they are more complicated than we thought. Some will ‘fold’ to a specific three-dimensional structure, whereas others refuse to fold and stay ‘disordered’. Disordered proteins are important to human biology and can act by binding other biomolecules. Interestingly, some disordered proteins will acquire structure when they bind, whereas others do not. We do not understand how this diverse protein behaviour arises from the DNA encoded sequence of amino acids. I will unpack this relationship using a new technique, where thousands of mutants, small changes to amino acid sequence, can be examined in a single experiment. The diversity of protein activities presents another problem – how can we control these processes, understand their importance in the cell and develop novel therapeutics? I will show that a new breed of drug-like compounds – cyclic peptides – have great potential to influence these new-found protein behaviours.”
Ina Maria Schiessl, 32, postdoctoral fellow
Ina will relocate from Department of Physiology and Neuroscience at University of Southern California, United States to set up her independent research group at the Department of Biomedicine, Aarhus University.
Grant amount: DKK 9,970,800
Project title: Unraveling the pathophysiology of endothelial cell plasticity in diabetic nephropathy by intravital multiphoton microscopy
Ina Maria Schiessl says: “Diabetes mellitus involves major functional complications of the kidney, which render this disease to the number one cause of end-stage kidney failure. One reason for this, are strong structural changes of the cells which built up the kidney blood vessels. This includes their migration away from the vessels, which leads to scarring of the kidney and destabilizing vessels, both decreasing kidney function. However, this mechanism is incompletely understood, because of the lack of techniques to track such structural and functional changes. In this project, I will use a novel microscopy-based technique, which I have developed in my previous work that allows us to study kidney structure and function simultaneously and over time in the same living animal. Hence, now we can visualize how those cells move away from the vessels, better understand why they do this and what functional consequences this has. Finally, we will test if this can be blocked by a new and promising anti-diabetic drug, which is already used in patients.”
Rune Busk Damgaard, 33, postdoctoral fellow
Rune will relocate from the MRC Laboratory of Molecular Biology, Cambridge, United Kingdom, to set up his independent research group at the Department of Biotechnology and Biomedicine, Technical University of Denmark.
Grant amount: DKK 9,999,873
Project title: Ubiquitin-dependent regulation of mTOR: linking immune signalling, cell growth, and metabolism in inflammation and cancer
Rune Busk Damgaard says: ‘‘Inflammation is the immune system’s normal response to infection or tissue damage. However, defects in the immune system or diseases that causes chronic inflammation can lead to development of cancer. Cancer cells are characterised by their ability to grow uninhibited. Astonishingly, although 15-20 % of cancers are caused by persistent inflammation, we understand very little about the cellular processes during inflammation that fuel cell growth and cancer development. During my postdoctoral work, I discovered that certain molecular signals used by the immune system to initiate inflammation also have the ability to control cellular metabolism, which determines if cells grow and divide. The research that I will undertake aims at exploring and understanding how the cellular processes that regulate inflammation connect with and control the cellular metabolism and growth signals that cancer cells need to form tumours. This connection may be key to understanding how persistent inflammation causes cancer, and this research could help identify the mechanisms of inflammation-associated cancer development new strategies for treating these cancers.”
Diego Vidaurre, 38, postdoctoral fellow
Diego will relocate from the Department of Psychiatry at University of Oxford, United Kingdom to set up his independent research group at the Department of Clinical Medicine, Aarhus University.
Grant amount: DKK 9,544,551
Project title: Disambiguating the neural threads of perception and cognition to characterise individual behaviour
Diego Vidaurre says: “No two brains respond equally to stimuli. The key idea of this project is that having an individualised picture of how the brain reacts to and processes information will enable a better understanding of each person’s unique psychology or pathology. For example, if we see someone’s face, multiple processes are initiated in the brain to manage the stimulus’ different elements: facial features, person’s identity, expression, elicited emotions, etc. If a wasp then stings us, competing neural processes emerge as our attention is rapidly directed to the pain. I refer to these different processes as neural threads. I will develop new computational models to disambiguate these threads in order to (i) better understand the principles of information processing in the brain, and (ii) characterise how this processing is unique to each person and relates to specific traits. I will apply this to the study of pain-processing to identify abnormalities in various prevalent chronic pain conditions.”
Hallas-Møller Ascending Investigators
Heather A. Boyd, 44, senior researcher
Department of Epidemiology, Statens Serum Institut
Grant amount: DKK 9,436,380
Project title: Lifelong and transgenerational cardiovascular and renal consequences of preeclampsia
Heather Boyd says: “As a group, women who have had preeclampsia have increased risks of cardiovascular disease and kidney disease later in life. However, we remain unable to identify the individual women most likely to develop these diseases. This is because we do not understand how preeclampsia changes a woman’s biomarker profiles, what consequences these changes have for her heart and kidney function later in life, and how these changes can be used to predict her future risk of disease. We also know very little about how preeclampsia affects the offspring’s cardiac and kidney function. With this research project, we will investigate biomarkers of cardiovascular disease and kidney disease in women who have had preeclampsia and develop new tools for cardiovascular disease risk prediction in these women. We will also investigate whether children born after pregnancies complicated by preeclampsia have increased risks of cardiovascular disease and kidney disease later in life.”
Martin Tolstrup, 43, Associate Professor.
Department of Clinical Medicine, Aarhus University
Grant amount: DKK 9,858,087
Project title: Viral specific T cells: Licensing the perfect killer
Martin Tolstrup says: “Many new developments in treatment of diseases such as cancer focus on gene therapy manipulations of immune cells which are costly, inherent risky and require sophisticated laboratory procedures for handling of the patient’s own cells. With this project, I propose to develop a new treatment concept that will seek to generate very high numbers of immune killer cells by a safe and low-tech vaccine directly in patients. These immune killer cells will then be used to kill diseased cells in the body. As a proof-of-concept I will use this concept to remove HIV-infected cells or cancerous B cells by studies in test tube experiments, in cells from patients and in humanized mice models. A successful project will open many new options for treatment of diseases caused by insufficient immune responses.”
Peter Brodersen, 43, Associate Professor.
Department of Biology, University of Copenhagen
Grant amount: DKK 9,998,654
Project title: Mechanistic basis of post-transcriptional gene regulation via N6-methyladenosine-modified messenger RNA
Peter Brodersen, who is a plant molecular biologist says: “Cells in plants and animals have very different functions. Nonetheless, all of the cells within the same organism contain the same genes. The cells acquire these different properties because distinct sets of genes are active in them. When a gene is active, it is first copied into so-called mRNA that is the direct template for subsequent protein synthesis. mRNA can be chemically modified, and such modifications have a crucial impact on mRNA function as templates for protein synthesis. This modification-system is deeply conserved: the same enzyme modifies mRNA in plants and animals, and the same factors read the modification code. In this project, we will find out how these deeply conserved readers of RNA modifications work: how they help cells grow, divide and mature, and how their regulatory functions relate to other systems of mRNA control.”
Rikke Nørregaard, 46, Associate Professor.
Department of Clinical Medicine, Aarhus University
Grant amount: DKK 9,423,750
Project title: Innovative Delivery Systems for Gene-Edited Stem Cell Therapy to Target Renal Fibrosis
Rikke Nørregaard says: “Chronic kidney disease (CKD) is a leading cause of mortality and the disease is currently affecting about 10% of the population. Current treatment strategies are ineffective at preventing disease progression. Our project will establish a targeted stem cell-based therapy to reduce renal fibrosis in CKD. We will genetically modify stem cells to enhance production and secretion of specific tissue-repair factors. The hypothesis is that gene-edited stem cells secreting tissue-repair factors can be utilized as a therapeutic modality to inhibit progression of renal fibrosis. Combining biochemical and integrative physiology which takes advantage of a broad variety of established models, including cell systems, animal models and human samples, we will study stem cell-based therapy for the treatment of renal fibrosis in CKD.”
Jens Bukh, 59, Professor.
Department of Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Hvidovre Hospital
Grant amount: DKK 10,000,000
Project title: Basic studies unravelling the nature of antiviral resistance using innovative experimental culture and animal systems of hepatitis C virus as models
Jens Bukh says: “A growing global health problem is antiviral resistance, which arises when viruses change (or evolve) to render drugs or vaccines ineffective. But how viruses develop antiviral resistance is poorly understood, and this limits our ability to combat infections and to develop compounds impervious to resistance development. We will use hepatitis C virus (HCV), which infects 71 million people and causes 400,000 annual deaths, as a model to study the mechanisms of antiviral resistance in unprecedented detail, as the inherent capacity of HCV to evolve and escape antiviral drug pressure remains a challenge. We will determine the key viral and cellular elements and molecules of resistance development, and how they interact to confer resistance. Thus, novel concepts pursued here will define how to prevent antiviral resistance in viral infections.”
Poul Nissen, 51, Professor.
Department of Molecular Biology and Genetics, Aarhus University
Grant amount: DKK 10,000,000
Project title: Structure and Mechanism of Key Pathways in Metabolic Control
Poul Nissen says: “The project is about solving structures of key receptors involved in nutrient uptake. A key system for control of our load of available sugar in blood stream versus deposition of energy resources is insulin and the insulin receptor. We will investigate how insulin activates the receptor to perform downstream control of other molecules and metabolic systems in the cell, and we will investigate its regulation in for example brain. Similarly, we will investigate a major amino acid (from protein in the diet) uptake system. Nutrient uptake is of key importance to all organisms and in humans it involves and controls numerous physiological processes and behaviour so that we seek food and eat properly without missing nutrients or overloading our system. Our studies will be highly enlightening for novel ideas and strategies in development of new medicine or procedures for treatment of metabolic disorders such as type 2 diabetes.”
Michael Lisby, 49, Professor.
Department of Biology, University of Copenhagen
Grant amount: DKK 9,995,405
Project title: Functional characterization of the ZGRF1 DNA repair helicase and its potential as a therapeutic target
Michael Lisby says: “Mutation of DNA helicases is responsible for a number of immunological disorders, infertility, neurodevelopmental defects, premature ageing syndromes and predisposition to cancer. We have discovered a new human helicase ZGRF1, which is important for repair of DNA lesions that block DNA replication. Replication-blocking DNA lesions are particularly toxic to cells, because they can lead to chromosome missegregation if not repaired before cell division. This is especially true for rapidly dividing cancer cells but also for cells undergoing rapid cell divisions during development and differentiation. With the proposed project, we will investigate the function and regulation of ZGRF1 and its implications for human health and disease to uncover its potential as a therapeutic target.”
Guillermo Montoya, 51, Professor.
Novo Nordisk Foundation Center for Protein Research, University of Copenhagen
Grant amount: DKK 10,000,000
Project title: GENED_2.0: From Molecular Mechanisms to the Next Generation of Genome Editing Tools
Guillermo Montoya says: “Genome editing is a technology that allows modification of the instructions contained in a genome and perhaps to “write” a new set of instructions to generate new genomes using the genetic code. This technology can be applied in therapeutics, especially in diseases where mutations produce illnesses and where a cell type is amenable for modification, such as for example bone marrow cells. Therefore, genome editing can be applied, to correct mutations causing rare diseases and certain types of cancer. To improve these applications, we need to get full mechanistic understanding of the “tools” that we use to initiate the modification. My proposal focuses in deciphering the working mechanisms of different CRISPR-Cas systems to provide better molecular scissors for various applications.”
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. Read more at www.novonordiskfonden.dk/en
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