IMSEC The IMmune Systems ECology Center; the center for immune-ecology network solutions
Excerpt from the Gravitation proposal IMSEC, submitted 10 May 2016 to NOW.
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in a web nutshell: page 2 of 8
Submitting organisation: University of Amsterdam http://www.imsec-center.com/
Applicants Founder Founder Founder Founder Founder Founder Founder Founder Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant Co-Applicant
Jannie Corina Reina Gerard Frits Ellen Marieke Hans V. Rob Marieke Gijs Marjolijn Mette Jef Aniko Remco René Jacques Timothy Martine Jacky L. Bas Pernette Anna Carlijn Willem Katy Maria
Borst Brussaard Mebius Muijzer Koning Van Donk Van Ham Westerhoff de Boer Van den Brink van den Brink van Egmond Hazenberg Huisman Korosi Kort van Lier Neefjes Radstake Smit Snoep Teusink Verschure Vilanova Voermans de Vos Wolstencroft Yazdanbakhsh
SILS/UvA &Div. Immunology/NKI NIOZ, IBED, UvA Molecular Cell Biology and Immunology/ VUMC Dept. of Aquatic Microbiology/ IBED/FNWI/UvA Dept. of Immunohaematol & Blood Transfusion/LUMC NIOO-KNAW, UU Dept. of Immunopathology Sanquin, UvA (co-coordinator) SBA/SILS/FNWI/UvA&VU&UoM (prime applicant) Utrecht University Radboud University UvA/AMC/ Tytgat Institute for Liver and Intestinal Research VUMC, Dept. Surgery UvA/Dept. Hematology UvA/IBED SILS, Neuor VU/TNO Sanquin/ UvA/AMC, Dept Hematopoiesis NKI/LUMC/Dept. Chemical Immunology UMCU VU/ FEW/ AIMMS VU/Dept Mol CellBiology; U Stellenbosch; Manchester VU/Dept. Systems Informatics UvA, SILS TUD Sanquin, Head, Lab for cell therapy WUR LU LUMC, Department of Parasitology
Scientific summary IMmune Systems ECology center; the center for immune-ecology network solutions Human well-being depends both on individuals’ health and on the ‘health/wellness’ of their environments. Both are under strong pressure. Blooms of toxic algae, global warming, invasive species, Multiple Sclerosis, Crohn’s disease and Rheumatoid Arthritis burden society and economy. Definitive solutions are lacking; focus has been on individual symptoms or components, whereas both human health and ecological wellness are extremely complex, networked processes, requiring network approaches.
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Stability and adaptability of these complex processes are determined by nonlinear networking between cells or organisms. Immune-mediated inflammatory diseases result from imbalanced cell networks, in time and space. Many ecological disasters stem from imbalanced population dynamics. Intrusions are not compensated for, with explosive rather than sedate outcomes. The nonlinear networks in immunology and ecology share (‘nonlinear, adaptive, selflearning’) complexity that has eluded comprehension.
IMSEC aims to discover what they have in common, by
comparing networks inside the human with networks outside (the environment). Human well-being may be improved by combining and implementing discoveries by scientifically connecting the disparate research areas of immunology and ecology. We aim to establish the world’s leading centre for the corresponding cross-disciplinary R&D field of Immune Systems Ecology, IMSEC, designed to lead the quest for solutions for networked health and environment problems.
IMSEC will
exploit the resulting serendipity and also provide new research needed to identify unappreciated common principles that determine balance in complex systems –ecological and immunological.
IMSEC will link the ecology and
immunology fields by implementing ecological principles (such as that diversity brings stability) in immunology, and by symmetrically implementing immunological principles in ecology. IMSEC immunologists and ecologists engage Systems biology to help bridge the existing gap between their disciplines. By modelling experimental systems mathematically and by analyzing them vis-à-vis potential common system principles, systems biology will empower progression from single-component to network approaches. This will enable IMSEC to establish new subtle and effective interventions that restore system balance through the strategic and therapeutic activation of homeostatic networks. Driven equally by top scientists of both genders, IMSEC will propel a new echelon of junior scientists of both genders into crossing boundaries of classical scientific fields.
The general properties of nonlinear networking
discovered, may shed new light on other areas of science, perhaps sociology, economics, and linguistics, with which IMSEC will connect. IMSEC will also open up its new area of science in many other ways, making data available to the worldwide community, enticing that community’s contributions, and financing researchers still developing their careers. IMSEC will interact reciprocally with policy makers, medical practitioners, and the general public to help enhance societal resilience to medical and ecological disasters. Summary and samenvatting of the research proposal in layman’s terms
Both our body and our environment maintain balance through a complex network of interacting factors. If something goes wrong, we see the overall result, like an illness or an ecological problem. Where the problem arose, and whether there are more problems simultaneously we do not know. IMSEC identifies and uses the common principles of networks in the body and environment, to find new ways for solving problems in immunology and ecology and potentially in many other complex systems: new treatments, new cures. Ons lichaam en onze omgeving blijven beiden in balans door een ingewikkeld netwerk van interacties. Gaat er wat mis dan is het eindresultaat een ziekte of een ecologisch probleem. Waar het probleem is ontstaan en of er tegelijkertijd meerdere oorzaken zijn, dat weten we niet. IMSEC identificeert en gebruikt onderliggende gemeenschappelijke principes van netwerken in lichaam en omgeving, om nieuwe manieren te vinden voor het oplossen van problemen in immunologie, in ecologie en wellicht daarmee in andere complexe systemen: nieuwe behandelingen, nieuwe geneeswijzen.
Key words
Immunology; ecology; computational systems biology; balance/homeostasis; resilience, immunity.
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The consortium The
consortium
international
leaders
members in
cell
are
biology,
immunology, ecology, systems biology and cellular therapy. Many have already set up entire research centers in NL or abroad (e.g. MCISB, DTC-ISBML, IBED, SBA), research consortia (e.g. Celiac Disease Consortium), or international collaborative
networks
(A
FACTT,
ICSB/ISSB, ISBE) in their own area. The founders see IMSEC as a growth model, program
where, of
through intensive
a
long-term integrative
research, truly new discoveries will be made concerning the robust and semiintelligent organization of many natural complex systems. How come these living systems can be so stable? But also, how come that some of their diseases are so persistent? The founders reckon that although they themselves are eager to make breakthroughs, more breakthroughs will come from this still unexperienced young faculty: IMSEC prepares avenues for career development of these junior scientists. Indeed, the consortium includes co-applicants from all career stages, with outstanding promise of achieving world-class levels in new scientific areas. The result is and will thereby continue to be a team of excellent players. Through its synergistic approach the consortium will provide new insights into complex cellular and ecological networks, establish a new school of science leading to academic advance and high-visibility publications, and yield novel scientific approaches. IMSEC will create insight in the effects of changes in environment (nutrition), microflora (antibiotics/probiotics) or composition of surveyor/immune cells (cell-specific therapies) on ecological balance. Moreover, IMSEC will be able to identify network-targeting therapies to remedy situations of imbalance in humans (chronic immune-mediated diseases/obesity) and in the environment (reduced biodiversity, unstable ecosystems). These novel classes of therapy will render strong socio-economical benefits, increase quality of life and promote resilience of our society to environmental threats. The insights created by IMSEC will thus not only affect the scientific community, but also generate novel levels of awareness and attitudes in therapy designers, policy makers and society as a whole.
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The scientific research programme Introduction
Disturbance of immune homeostasis underlies many crippling diseases. Similarly, disturbance of
eco-systems is a constant threat to our natural surroundings. While the disturbance may be precipitated by a single catastrophic event, like serious trauma or large oil spills, it is more likely that multiple sequential events exhaust the buffering power of complex systems, culminating in a disbalance that can no longer be restored through natural regulation. Identifying early indicators of disbalance may allow timely interventions that prevent full blown disbalance or restore the balance. Our approach may thus have far-reaching implications as it may severely reduce the burden of immune mediated diseases and help to preserve the integrity of our natural surroundings that is suffering from over-population. Both immune- and ecosystems are underpinned by complex, nonlinear networks. The network’s behavior depends on many interactions taking place at the same time. Understanding network behaviour therefore requires precise knowledge of many interactive properties. Until recently, such information was not available for any complex system. However, we are about to overcome this critical barrier to scientific progress: functional genomics and imaging at high spatial resolution now allow measurement of millions of properties of living systems at the same time. Computing has improved so much that it is now possible to use the enormous amounts of data for simulation and prediction of the behavior of those complex systems. Network properties such as hubs (points that reside on many routes) and redundancy (parallel pathways) have been noted in biochemical networks and have been related to robustness, stability and homeostatic control. However, the more elusive and fascinating properties of complex networks have not been similarly addressed, such as immunity or adaptation to environmental challenges, in all its diversity. Lacking is the elucidation of the general principles underpinning the nonlinear behavior.
The IMSEC idea:
Take two complex, but experimentally accessible biological systems and examine whether
complex properties of the one system are also found in the other and vice versa. This will reveal novel principles operating in both systems that may be broadly applicable to other networks as well.
The IMSEC approach:
IMSEC chose two areas of biology that are far apart, yet both exhibit different highly
complex properties, i.e. immunology and ecology. IMSEC’s founders consists of 3 eminent ecologists, 4 excellent immunologists and a systems biologist expert. They devised a research program in which new junior staff will empower execution of the above ideas. This program aims to integrate the 3 research fields in multiple ways into virtually complete coherency, associating all the necessary ecological, immunological and systems biology perspectives: 1.
We will implement the integrative discipline systems biology
2.
We will use a common toolbox (WP5) for data integration, data analysis and experimental procedures
3.
We will examine in 4 teams of an ecologist, an immunologist and a systems biologist whether 2 ecological principles of complexity also apply to immunology and whether 2 such immunological properties also apply to ecology
IMSEC has been optimized to maximize the synergy between its immunology, ecology and systems biology constituents.
The IMSEC novelty and potential:
No such integration between immunology, ecology and systems biology
exists. Discovery of immune principles in ecology and ecology principles in immunology will move both fields. The discoveries made in the system where ecology and immunology integrate (the gut) will realize a next level of synergy, approaching truly integral understanding with corresponding therapeutic implications for the environment and human health.
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The four cross-fertilizing principles: IMSEC will examine whether:
The The The The
ecological principle that ecological principle that immunological principle immunological principle
diversity begets stability, also applies to immunology, WP1 resource variation affects stability also applies to immunology, WP2 that specificity begets stability, also applies to ecology, WP3 that memory begets stability, also applies to ecology, WP4
An integral IMSEC research crew: IMSEC will appoint a junior research crew, with ecology, immunology and systems biology backgrounds, that will carry out the day-to-day research. They range from tenure trackers to PhD students, and from technicians to theoreticians
IMSEC is an open but integrative research program, career-mindful: IMSEC is a proposal for a research program rather than a project. It therefore leaves much space for new developments. Many PhD studentships and postdoc projects can still be applied for (see yellow fields in the Tables) by consortium PIs in open competition managed by the SAB. Also equipment and technician positions are open for competitive bidding. In this way, the IMSEC Research Infrastructure (see WP5) will become an international research hub that will also serve the corresponding international communities.
IMSEC research structure: Themes in 4 work packages + 2 support WPs IMSEC will begin with examining the relevance of 2 ecology principles for immunology and 2 immunology principles for ecology. The 2 ecology principles are that (1) species diversity increases stability and (2) stability of ecological populations can depend strongly on resource availability. The 2 immunology principles are that (3) specificity of response is required so as not to destabilize the system (WP3) and (4) multi-layered memory can provide a sheer endless robustness. Each of these themes will be elaborated in a corresponding work package with identifier Diversity (WP1), Stoichiometry (WP2), Specificity (WP3) or Adaptation (WP4). The many H2020 research projects of the consortium members will all be approached for linking up. WP5 [provides data managmetn and interpretation support to WP1-4. A dedicated WP will service all WPs by providing management support.
Connections to the Dutch National Science Agenda (NWA) The IMSEC initiative fits perfectly with several of the Exemplary Routes of the National Science Agenda, in particular 1. Personalized Medicine, 2. Regenerative Medicine, 3. Quality of the Natural Surroundings (Kwaliteit van de Omgeving), and 4. Professional Big Data Management (Big Data Verantwoord Gebruiken). Our initiative will facilitate the generation of crucial connections between these four exemplary routes where knowledge that is already developed in one area, will be applied in other areas and vice versa. A crucial element is the identification of common mechanisms through which ecological and immunological balance is maintained and disturbed, in order to define unifying strategies to restore balance. For this a systems biology approach will be applied that is fed by the utilization of existing big datasets and the generation of high-dimensional data sets that allow a 3-dimensional analysis of complex eco- and immune-systems. IMSEC will make use of recent technological innovations that allow the generation, integration, interrogation, interpretation and visualization of such high-dimensional datasets, all crucial steps towards the generation of innovative approaches to prevent and combat a multitude of crippling chronic diseases and ensure environmental stability in a rapidly changing world. As such IMSEC will specifically address issues relevant to 26 of the 140 cluster questions formulated in the National Science Agenda:
N003: Wat is het belang van biodiversiteit en hoe behouden we deze
N004: Hoe functioneren ecosystemen en hoe gevoelig zijn zij voor milieu-invloeden?
N005: Welke rol spelen micro-organismen in ecosystemen en hoe kunnen we deze inzetten voor gezondheid en milieu?
N008: Hoe verandert het klimaat, inclusief extreme weersomstandigheden, en wat zijn de gevolgen ervan?
N011: Hoe kunnen we in de toekomst het water zorgvuldig beheren?
N072: Hoe bevorderen we gezondheid en voorkomen we ziekte via een gezond(e) leefstijl en gedrag?
N077: Wat is de bijdrage van niet-genetische factoren aan persoonlijke eigenschappen en ziekteprocessen?
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N080: Kunnen we de factoren die een rol spelen bij het ontstaan en de instandhouding van onbegrepen langdurige lichamelijke klachten beter begrijpen en daardoor deze klachten beter behandelen?
N081: Hoe gaat kennis van genetica een rol spelen in begrijpen van, screenen op en behandelen van (zeldzame) ziekten?
N85: Elke tumor is anders: hoe kunnen we de ziekte kanker goed genoeg begrijpen om een behandeling voor elke vorm ervan te kunnen ontwikkelen?
N086: Darmziekten en in het bijzonder de relatie tussen onze darmflora en gezondheid: hoe kunnen we de darmflora effectief beïnvloeden?
N087: Hoe ontstaan diabetes type 1 en 2 en hoe kunnen deze eerder worden opgespoord en vervolgens op individuele basis te worden behandeld?
N094: Hoe maken we de gezondheidszorg kwalitatief zo goed mogelijk, maar houden we haar betaalbaar?
N095: Hoe kan de gezondheidszorg, onder andere door gebruik te maken van biomarkers, meer gericht worden op de uniciteit van een persoon?
N096: Hoe komen we aan een betere diagnostiek, betere behandelingen en betere vaccins voor afweerstoornissen en infectieziekten?
N097: Hoe blijven we micro-organismen de baas in gezondheidszorg, veehouderij en milieu?
N098: Hoe kunnen we doorbraken binnen het fundamenteel-biomedische onderzoek beter vertalen naar de ontwikkeling van nieuwe medicijnen?
N099: Hoe kunnen we met behulp van een groter begrip van het leven, nieuwe targets identificeren voor moleculaire therapieën, antibiotica en antivirale middelen?
N101: Kunnen we modellen van het menselijk lichaam ontwerpen en slimme technologie gebruiken voor gezondheidsvoedings- en toxiciteitsonderzoek en daarmee tegelijkertijd het proefdiergebruik drastisch verminderen?
N102: Hoe kunnen we nieuwe geneesmiddelen en -wijzen ontwikkelen om zo vitaal en gezond mogelijk te blijven?
N103: Hoe kunnen we de mogelijkheden en grenzen van de medische vooruitgang begrijpen en beoordelen?
N104: Hoe ontwikkelen we minimaal-invasieve technieken en interventies voor diagnose, prognose en behandeling van patiënten?
N105: Hoe kunnen big data en technologische innovatie (e-health) bijdragen in de zorg?
N112: Big data: kunnen we grote datasets en het verzamelen daarvan benutten voor het realiseren van waarden, het genereren van inzichten en het verkrijgen van antwoorden?
N124: Hoe slaan we de brug tussen verschillende schalen bij het modelleren van dynamische systemen, zoals stromingen van en in vloeistoffen en gassen?
N136: Cellen zijn de bouwstenen van het leven. Hoe werken ze en wat kunnen ze ons leren over levens¬processen?
N138: Hoe en waarom doen dieren wat ze doen?
Budget 10-year plan budget: 35 M€
