NWO

NWO Gravitation: Institute for Chemical Immunology

LUMC PI: Sjaak Neefjes, PhD (Dept. CCB)

Startdate: 2014 - End date: 2024

Our immune system protects us against external pathogens and internal threats such as impaired body cells. Immune system malfunction is a critical element to many conditions, including infectious diseases, but also cancer and autoimmune disorders such as rheumatism and arthritis. The immune system is very powerful, but must continually work to find the right balance between tolerance and response. The Institute for Chemical Immunology (ICI) develops chemical compounds that can activate or suppress the immune system precisely. By combining immunological knowledge with advances in chemistry, the ICI is working on a new generation of medicines for common diseases such as cancer and rheumatism. 

NWO Gravitation: Netherlands Organ-on-Chip Initiative

LUMC PI: Prof. Christine Mummery, PhD (Dept. Anatomy)
Start date: 01 October 2017 – End date: 30 September 2028

Cardiovascular, gastrointestinal and brain diseases are major health burdens in developed countries. Without new approaches for prevention and novel therapeutic solutions, these conditions are expected to increase to epidemic proportions in aging populations. The development of new treatments is however hampered by the inability of current model systems to capture features of human tissue and disease. Therefore, it is essential that our traditional methods for health research are redesigned. Human disease-specific stem cell and organoid technologies are increasingly recognized as cutting-edge research platforms for functional genomics, disease modeling and drug target discovery in both academic and commercial sectors. Combined with biophysical and biochemical assays, multicellular microfluidic structures, they are already accelerating drug repurposing and supporting drug target discovery. NOCI aims to develop these new approaches, designated as â??Organ-on-chipâ??, and achieve a paradigm shift from empirical treatment of symptoms of disease to cures based on correcting the underlying cause. The six main applicants are internationally leading scientists and physicians in the diverse fields of stem cell biology, microfluidics engineering, microbiota and systems genetics and pathophysiology of cardiovascular, neural and intestinal disease. They have already established collaborations through the Institute for Human Organ and Disease Model Technologies (hDMT), founded to co-develop Organs-on-chip. Our mission is (i)to make complex human tissue and organ systems in Organ-on-chip devices that model cardiovascular, brain and gastrointestinal diseases; (ii)provide readouts of disease pathology as diagnostic, disease-state and therapeutic response biomarkers; (iii)integrate the human (intestinal) microbiome and inflammatory component of disease into chips; (iv)use the models to identify/engineer disease mutations, genetic modifiers and variants predisposing to disease for prevention, personalized medicine and new therapeutics; (v)replace/reduce animal experiments. NOCI involves three Scientific Challenges: (S1) mastering human stem cell and organoid biology in complex multicellular structures for Organ-on-chip formats; (S2) mastering biomarker resolution in monitoring disease; (S3) mastering non-invasive methods to monitor signal transduction, gene expression and epigenetic regulation. Each challenge focuses on fundamental questions regarding cells, disease pathology, its confounders, and materials and formats of microfluidic devices that capture the biomechanics, biochemistry and molecular biology of the tissue niche. This multidisciplinary approach will result in better understanding of human tissue biology and disease, communication between tissue cells, blood vessels, (body) fluids and component cytokines and hormones, biomaterials and the microbiome, and the effects of genetic variants and mutations. The resulting knowledge, experimental tools and disease models will be integrated into three Technological Challenges covering the Organ-on-chip process, specifically: (T1) chip design and production, including controlled biomechanics, biochemistry and fluid flow; (T2) integration of stem cells and organoids; (T3) relevant biomarkers as readout of the disease. Through our existing links with the pharmaceutical sector (in part through hDMT), we will showcase the usability of complex human tissue models for screening new treatments and repurposing existing drugs. This is at the heart of human stem cell-, organoid- and Organs-on-chip research in the Netherlands. We expect our program to impact Dutch biomedical research beyond the diseases used as exemplars and the decade for which the work is planned.

NWA-ORC Bioclock Consortium BioClock: BioClock: The Circadian Clock in Modern Society

LUMC PI: Prof. Joke Meijer, PhD (Dept. CCB)
Start date: 01 June 2021 - End date: 31 May 2027

Since the start of life on Earth, virtually every species evolved under a 24-hour light-dark cycle, giving rise to an internal biological clock that is remarkably well-conserved throughout a wide range of plant and animal species. In most species, specialised photoreceptors respond to specific wavelengths and intensities of light, serving as the principal external signal to the internal clock. Importantly, biological rhythms are genetically encoded according to very similar principles among species. In general, a strong rhythm promotes health, while a disruption of rhythms can exacerbate or even cause a wide range of mental and physical diseases. Since the introduction of shift work in the 1850s, transatlantic flights in the 1960s, and by the pervasive use of artificial light at night, we have been increasingly ignoring our biological clock, and those of the organisms in the natural environment. Due to the high population density, extensive industrialisation, and the widespread presence of greenhouses, the Netherlands is one of the most light-polluted countries in the world. This has dire consequences for our clocks and for health. Preserving our clock has drawn growing interest in society, reflected by the many questions posed via the NWA with respect to: i) optimising our daily schedule in order to improve our health, mood, and sleep quality, particularly among adolescents and the elderly, ii) optimising the efficacy of medical treatments, improving clock function in patients, and developing clock-enhancing tools, and iii) protecting our fragile ecosystem and maintaining our planetâ??s rich biodiversity. In this project, a unique consortium of scientists, clinicians, local governments, and other societal partners will undertake an ambitious but attainable project designed to directly address these key issues, ultimately benefiting not only our own health and well-being, but also the world around us.

NWA-ORC CURE4LIFE: Development and societal impact of stem cell based genetic medicines

LUMC PI: Prof. Frank Staal, PhD (Dept. Immunology)
Start date: 15 September 2022 – End date: 14 September 2027

For a number of rare genetic diseases, lifelong cure can be obtained by correcting the genetic defect in the patientsâ?? own blood stem cells. Many curative gene therapies do not reach patients for reasons other than a lack of treatment quality. We propose to develop platform infrastructure that can be used for many diseases rather than every time focusing on one approach unique for each disease. Simultaneously we address challenges regarding the regulation, reimbursement and public acceptance of these therapies in a knowledge hub for dialogue with society.

NWA-ORC LymphChip: Developing immunocompetent human organ-on-a-chip models with integrated lymph drainage for drug discovery and testing

LUMC PI: Valéria Orlova, PhD (Dept. Anatomy)
Start date: 19 September 2021 – End date: 31 December 2026

Instead of using animals, the effects of drugs or therapies can be tested using miniature tissue models, mimicking organ responses. However, none of these models currently include the lymphatic and immune systems, despite their importance to our health. We will develop “organ-on-chip” models with integrated lymphatics, providing a precision tool in the battle against immune-related diseases.

NWA-ORC ECOTIP Identifying tipping points of the effects of living environments on the ecosyndemics of lifestyle-related illness

LUMC PI: Prof. Jessica Kiefte-de Jong, PhD (Dept. PHEG)
Start date: 01 February 2024 – End date: 31 January 2029

An ecosyndemic is characterized by adverse disease interactions that result from an adverse living environment. Our goal is to identify the tipping points where the population's resilience to adverse living environments deteriorates into an ecosyndemic, and to determine the optimal conditions and timing for effective interventions from the perspectives of policy makers, healthcare professionals, and citizens. To do so, we will conduct advanced data analysis of historical data on indicators of the living environment and population resilience. We will then translate our findings into actionable measures for policy makers, healthcare professionals, and citizens, in collaboration with a multi-actor learning community.

Roadmap: Innovative Stem Cell Technology Infrastructure for human organ and disease models

LUMC PI: Prof. Christine Mummery, PhD (Dept. Anatomy
Start date: 01 August 2023 – End date: 31 July 2033

Human stem cells can be used to create models that mimic the human body, allowing understanding of healthy tissue physiology and disease mechanisms. The two types of stem cells individually have strengths but also shortcomings that could be overcome by their combination to provide unprecedented human organ and disease models. To our knowledge, this has not been done before. We will establish a national infrastructure that provides supporting services to the research community to enable combination of these two stem cell types. We thereby facilitate and stimulate the development and use of human stem cell-based organ and disease models.