Systems Biology Approaches to Immune Modulation and Inflammation - Workshop Report
[ PDF (1.28 MB) | Help ]Table of Contents
Workshop Executive Summary
Background
Introduction
Workshop Goals and Objectives
Keynote Speakers
Breakout Session 1 - Theme Specific
Breakout Session 2 - Multidisciplinary
Summary
Next Steps
Appendix 1 - Participant List
Appendix 2 - Workshop Agenda
Appendix 3 - Breakout Session Groups
Appendix 4 - Breakout Group Questions
Workshop Executive Summary
On January 22nd and 23rd, 2008 the Canadian Institutes of Health Research (CIHR) Institute of Infection and Immunity (III) hosted a one and a half day invitational workshop in Montreal to explore the possibility of applying a systems biology approach to the study of immunotherapy, inflammation and immune-based diseases. Recent advances in the application of molecular technologies in biological research have generated vast amounts of data and created extensive databases containing information vital to our understanding of both normal systems and disease processes. However, in order to successfully mine these databases and apply the information they contain to improve the prevention, diagnosis, management and treatment of immunological diseases it is imperative to find ways to facilitate the integration of mathematical, engineering and computational skills into traditional biological research. It is increasingly recognised that a systems approach to research, in which whole systems can be observed and modified, offers advantages over the historical, reductionist approach of examining individual components of systems in isolation from each other. To date, there are few centres in Canada with a robust systems biology focus and even less that are focusing on immune-modulated diseases or therapies.
The workshop brought together systems biologists, immunologists and clinical immunologists to asses the current status of systems biology research in Canada and abroad, and to advise III on the best course of action to encourage the application of systems biology approaches to research on immune modulation and inflammation. It is hoped that the application of these new technologies will improve our understanding of why many traditional immunostimulatory or immunosuppressive therapies are either only partially effective or have adverse side effects.
Following a series of plenary talks by keynote speakers, workshop participants considered the existing 'state of the art' in systems biology and immunotherapy and potential mechanisms for combining multiple fields of expertise. Both immunologists and systems biologists expressed enthusiasm for collaborations that would facilitate the integration of whole systems approaches to the study of immune-mediated diseases and immunotherapy and both groups recognised the advantages of such an approach in clinical research.
From the outset, it was apparent that one of the greatest challenges would be creating effective avenues of communication between the groups and establishing a common language to enable biologists and natural scientists (mathematicians, engineers, computational experts) to work together. It was noted that the regular operating grant system is not ideal for supporting these required cross-linkages and providing multidisciplinary training opportunities. It was also evident that a significant investment of new funds and multiple partnerships would be required to support large multidisciplinary centres capable of moving the field forward at a rapid pace. Although in favour of a bold new initiative with unique components, workshop participants also recognised that incremental, strategic investment would be key to building sustainable capacity and establishing long-term collaborations. Several existing CIHR programs offer promise in this regard, such as the Strategic Training Program in Health Research (STIHR) and the Collaborative Health Research Projects (CHRP) partnership between CIHR and the Natural Science and Engineering Research Council (NSERC). Both these competitions have upcoming application deadlines. There is also a need to make links between relevant initiatives funded by III and other national and international opportunities in the area of systems biology. III staff, in consultation with Institute Advisory Board members, will explore potential partnership opportunities to enable the launch of a large-scale research initiative.
III is committed to making the integration of systems biology into health research a reality through the promotion of this approach in research on immune-mediated diseases and immunotherapy.
Background
The Canadian Institutes of Health Research (CIHR) Institute of Infection and Immunity (III), in its 2007-2012 Strategic Plan, identified five strategic research priorities, one of which was "Immunotherapy: New approaches through systems biology". As a first step towards developing a research agenda to address this priority, a workshop was convened to bring together researchers from the systems biology, basic immunology and clinical immunology communities to initiate a dialogue between these diverse groups. On January 22nd and 23rd, 2008 more than 50 invited participants, including representatives from several potential partner organizations and other CIHR Institutes, came together for a day and a half to explore research opportunities of mutual interest. The supporting documentation, including the participant list, workshop agenda, and breakout session questions is provided in Appendices 1-4.
Introduction
Modern medicine has evolved to have a predominant emphasis on reductionist science, in which researchers focus on individual components in isolation from the system as a whole. For many diseases this separation of the whole into multiple parts ignores the interactions between these parts and their combined influence in disease pathogenesis. Rarely is an immune or infectious disease process caused by a single modality or failure, but rather by multiple factors acting on many components, either in sequence or simultaneously, to bring about changes in system-wide behaviour. This is particularly evident for most chronic diseases, including autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and Type 1 diabetes.
Systems biology approaches involve a coordinated study of biological systems (from molecules to whole organisms) by: investigating the components of cellular networks and their interactions; applying experimental high-throughput and whole genome techniques; and integrating computational methods with experimental efforts. Immunotherapy is a broad discipline that includes an array of strategies based on the modulation of the immune system to achieve a prophylactic and/or therapeutic goal. Examples of immunotherapy approaches include vaccines, immunosuppressive/stimulatory drugs, biological therapies (e.g. monoclonal antibodies, cytokines) and cell based therapies (e.g. stem cells, dendritic cells, T and B cells).
By applying a systems biology lens to immune modulation it is hoped that the treatment of immune-based diseases can be enhanced through the development of individualized and/or synergistic treatments, minimized interventions, multidimensional uses of medications, time and space sensitive treatments and predictive medicine. The application and integration of systems biology approaches to traditional medicine through a focus on immune modulation is likely to enhance our understanding of many normal biological functions and disease conditions.
Workshop Goals and Objectives
The primary goal of the workshop was to create effective communication channels between systems biology and immunology researchers with the objective of learning how to use systems biology techniques to enhance our understanding of the processes involved in immune modulation, immunotherapy and inflammation. The workshop provided an opportunity for participants to learn about the state of the art in systems biology and immunotherapy from the four keynote speakers and engage in theme specific discussions, in which participants were broadly grouped according to area of expertise. Finally, participants were divided into multidisciplinary groups and tasked with developing a 'mock' research proposal in a process that would encourage them to identify and address the challenges in applying systems biology techniques to solve immunological problems. The overarching workshop objective was to promote partnerships, create opportunities for the sharing of technology platforms around clinical immunology networks, and to provide III with advice on how to encourage the integration of systems biology into studies on immune modulation.
Keynote Speakers
Keynote Speakers were invited as experts in their respective fields and asked to provide workshop participants with a broad overview of their particular scientific discipline and also act as a valuable resource during the later breakout sessions. All four speakers identified some of the potential challenges that might be faced in integrating the two approaches, along with examples of situations or programs in which these challenges have been successfully overcome. What follows is a brief synopsis of the most salient points of the presentations. Many of the presentations are available in whole, or in part, through the speakers' host institution websites.
"Bioinformatics and Systems Biology: Partners for life" - Dr. Francis Ouellette, Associate Director of Informatics and Biocomputing,
Ontario Institute of Cancer Research, Toronto
This presentation focused on the interdependency between bioinformatics and systems biology; the challenges facing the research community in integrating different technologies and applying them to complex health issues; and the importance of open access to information and resources in moving the science forward. Emerging as new disciplines in the early 1990s, informatics and biocomputing are now central to all biomedical research, driven by the escalating data generation of modern biological technologies such as DNA microarrays and high-throughput genotyping. Bioinformatics serves to turn large-scale data generation into data analysis quickly and accurately, providing new insights into complex biological processes. Systems biology involves the integration of existing diverse and multivariate experimental data using computer tools and biological databases to generate new knowledge about whole systems. Whereas bioinformatics is effective in generating analyses of the parts of a system, systems biology focuses on stringing these parts together to build whole systems and gain an understanding of what happens when things malfunction, such as in disease. The continuum from bioinformatics to systems biology moves through small molecules, metabolites, proteins, DNA/RNA, genes, genotypes to whole organisms, populations and ecosystems. An appropriate analogy would be a do-it-yourself construction kits such as those popularised by IKEA. Bioinformatics and biocomputing would generate all the necessary knowledge to produce the parts and systems biology would provide the manual for putting the parts together to construct the item. Many of the necessary "parts" or resources are already available in the form of extensive biological clones/reagents/libraries, software applications, multiple databases and open access websites and journals. What is required now is adequate funding to maintain and link these resources and to bring biologists, bioinformaticians and system biologists together in integrated networks underpinned by strong training programs and supplemented by short-term workshops. The presentation was followed by a brief discussion during which the bioinformaticians and statisticians present expressed a willingness to participate in "biologically-orientated" research, particularly if they were engaged in projects from the first stages as an integral part of a multidisciplinary research team.
"Restoring Tolerance in Autoimmunity" - Dr. Michael Ehrenstein, Centre for Rheumatology, University College, London, UK
Autoimmune diseases are a consequence of perturbations in the normal immune response leading to a breakdown in immune tolerance, manifested as an immunological attack on the body's normal tissues. Examples of some of the more common autoimmune diseases include rheumatoid arthritis (RA), multiple sclerosis (MS), lupus erythematosus (SLE), inflammatory bowel disease (IBD), and Type 1 diabetes. Historically, treatment for these diseases has relied on non-specific immunosupression using a variety of drugs (e.g. Corticosteroids, Gold and Methotrexate) with partial effectiveness and often serious side effects. There are also cases where drugs developed for other clinical uses, such as statins for serum cholesterol reduction, have been shown to be effective in the treatment of certain autoimmune diseases, presumably through known immunomodulatory effects. In the last decade, however, new biological therapies have become available which appear to be far superior to previous treatment options. This presentation provided thought provoking information on how these new treatments might be working and the pitfalls in extrapolating data from animal models into clinical situations. New biologic agents offer improved specificity against the traditional therapeutic targets, which include depletion of cells from the inflammatory site, inhibition of abnormal cellular interactions and regulation of effector mechanisms such as cytokine neutralization. However, the use of different agents that target the same molecule can have very different therapeutic effects. For example, of two drugs (infliximab and etanercept) targeting the same cytokine, tumour necrosis factor (TNFa), only infliximab is effective in the treatment of Crohn's disease, whereas both drugs are effective treatments for RA patients. In the case of RA, it appears that infliximab acts by modulating the effector function of the defective regulatory T-cells (Tregs) found in RA patients, but it does so through a different mechanism than the drug etanercept. The evidence presented on the complex interactions between TNF, regulatory T cells and anti-TNF agents suggests that these new biological therapies are highly effective treatments and offer the hope of long term remission in autoimmune disease. From the experimental data presented, it is clear that we have a wealth of information on the mechanism of one drug, infliximab, on Treg populations both in vitro and in vivo. However, an even deeper understanding is needed to predict which patients will respond to which drugs, and what the potential side effects might be in different populations. This information will be needed if we are to advance to personalized medicine. Many valuable insights have been gained from the use of experimental models as predictors of human disease. However, there are also instances in which experimental data has not translated into clinical benefits. For example, the use of anti-TNF agents in MS provided encouraging data in a mouse model system but in fact worsened the disease in MS patients. Such cases highlight the importance of research in human systems and the value of clinical research. The integration of systems biology into clinical research might be one approach for advancing our understanding of disease pathogenesis resulting in improved prevention and treatment modalities.
"How to Develop a Systems Biology Program useful to Biologists (including immunologists)" - Dr. Ron Germain, Laboratory of Immunology and Program in Systems Immunology and Infectious Disease Modeling, NIAD, NIH, US
The goal of this presentation was to provide linkages between systems biology and immunology and to set the stage for later discussions on potential systems biology approaches to immune modulation. Biological systems are extremely complex and although a great deal of information is already known about the multiple components of the inflammatory response there is still a gap in our understanding of how these components actually interact or may be used in a predictive capacity to simulate biological behaviours. A systems biology approach builds on genome sequence data, expression profiling, proteomic analysis, imaging datasets, nanostate analysis, global RNAi and chemical library screening to produce network organization of cell components, engineering diagrams of differentiation pathways and models for simulation and prediction. Through a series of multi-media simulations, the presentation demonstrated the remarkable capabilities of a systems biology approach that integrates computer, mathematical and biological technologies. The capabilities of such an approach far exceed the traditional "cartoon style" custom model building when applied, for example, to TCR recognition and the early signalling events in T cell activation. For biologists to take advantage of these cutting edge modelling tools, however, the gap must be bridged between computer science, mathematics and biology. The program in Systems Biology and Infectious Disease Modelling (PSIIM) at NIAID has succeeded in doing this through a computer program called Simmune that allows a biologist to construct and run complex models with all the necessary mathematics handled "in the background". Simmune supports computational models from molecular interactions to multi-cellular systems, as demonstrated in an impressive series of simulations. Using systems such as Simmune, a permanent detailed repository of a biologist's knowledge is created that others can access and use through linkages to public and private databases and search engines. Systems biology requires a multi-component integrated program that brings all the necessary areas of expertise together, as exists at PSIIM, and encourages cross-discipline collaboration. Through this mechanism, hypotheses can be tested, refined and retested, creating new pathways for biomedical discovery. The presentation was followed by a discussion on the pros and cons of a centralized model in which systems biology capacity is incorporated within individual institutions vs. a "distributed" model across multiple institutions. Many of the systems biology researchers expressed a reluctance to be seen as an external resource to be tapped into "as needed" and would prefer a more integrated model in which research teams included systems biology expertise as part of the core group.
"The Ottawa Institute of Systems Biology: Bridging systems biology and diseases" - Dr Daniel Figey, Ottawa Institute of Systems Biology, Ottawa
The final presentation described one example of a Canadian group currently engaged in systems biology research. The Ottawa Institute of Systems Biology, located within the Department of Medicine at the University of Ottawa, has a mandate to create a systems biology group focused on human disease that includes training and education. The Institute takes the technological view of systems biology, as defined by Leroy Hood, as integrating technology, biology and computation. The institute intends to:
i) develop a systems biology program aimed at the understanding of human diseases
ii) develop robust platform technologies for high-throughput experiments for systems biology studies and for other projects
iii) develop innovative high-throughput technologies to probe increasing numbers of biomolecules from cells to tissues and develop novel bioinformatics tools and mathematical modeling approaches for systems biology
The Institute is actively recruiting faculty (several of whom were workshop participants) with a variety of research interests such as biology, biochemistry, biostatistics, biomathematics, x-ray crystallography, neurosciences, and computational modelling. However the long term goal is to collaborate as much as possible across the different disciplines rather than try and recruit from each one. For example, links have already been established with researchers working on Alzheimer disease and stroke, two areas where initial projects will focus. Projects will integrate genomics, proteomics and lipidomics with imaging to provide a novel view of the brain in cerebrovascular, Parkinsons and Alzheimer disease. It is unlikely that success will come overnight as there are many different solutions to apparently simple problems (e.g. ways to boil water) requiring a combination approach and an acceptance that there may be early failures. There are also challenges in recruiting multidisciplinary teams and forging productive and long term collaborations across fields and between institutions. In terms of the application of systems biology approaches to immune modulation, the need to determine the "low hanging fruit" was identified, preferably in an area where a good animal model exists and tissue samples are available.
Breakout Session 1 - Theme specific
Workshop participants were divided into three groups, broadly based on area of expertise, to discuss the state of the art in their respective research areas and to consider approaches to integrating systems biology into the study of immunotherapy/inflammation research. Each group was provided with a series of questions (Appendix 4) to help guide the discussions. The main points discussed and the conclusions reached are described briefly below.
Group 1 - Systems Biology
Group 1 defined systems biology as a focus on molecular systems and cell-cell interactions and immunotherapy as a two pronged approach - using the immune system to treat disease (e.g. vaccines, cancer) and treating diseases of the immune system (e.g. autoimmune diseases). As described in the earlier presentations, the group agreed that the key to success rests on the ability to integrate genome-scale information (genomics, proteomics) in a biological context (pathways, networks) in a way that enables examination of system level properties like signal propagation, robustness and processes over time. Emergent behaviour is difficult to predict from an examination of the parts in isolation, rather it is necessary to gather all the required information to predict function and outcomes using an iterative approach. A good example of this system in action is the innateDB project in British Columbia, which aims to provide a knowledge base of the genes, interactions and signalling responses in the innate immune responses of humans and mice to microbial infections.
The challenges facing systems biologists and immunologists include finding both a common language with which to communicate effectively and better ways to sort through the huge amounts of existing data to select the few things that can be successfully studied in the laboratory. The existing funding mechanisms are not necessarily supportive of researchers moving between fields and grant applications that combine research disciplines are often difficult to review under the current, predominantly discipline-specific, peer review system. In addition there are scarce resources available to maintain and support existing databases and software. To address these challenges the group suggested that the CIHR resource support grants be re-introduced and that the integration of systems biology approaches to the study of immune modulation be a staged process that includes project support, catalyst grants and extensive cross-training opportunities. Specifically, the group recommended that even with scarce new funding, the communication process could be facilitated through student exchange between laboratories, catalyst/seed grants, co-supervisors from different fields for students, multidisciplinary workshops, short-term (2-3 days) training programs and dual supervision of students. If modest new funding became available the recommendation was for larger scale training programs, perhaps as part of the CIHR strategic training initiative and programs such as Emerging Team grants and specific Requests for Applications (RFAs). There was a broad consensus that if systems biology approaches are to succeed, a long term commitment must be made to support the integration required and that ideally a large sum of money, in the region of $500 million, would be necessary to establish and maintain this new approach to health research. Such a commitment would require multiple partnerships and considerable new financial investment.
Group 2 - Clinical Autoimmunity
Members of this breakout group included representatives from five of the six clinical autoimmunity teams recently funded by III and partners under the Clinical Autoimmunity Team Grant initiative. This initiative was launched to support collaborative, multidisciplinary teams engaged in autoimmune research in a clinical setting. Funded projects focused on several different autoimmune conditions including IBD, pediatric disease, psoriasis and psoriatic arthritis, inflammatory arthritis, SLE and multiple sclerosis.
The group agreed with earlier definitions of systems biology as integration of technology (large data sets), biology and the clinical information to model both normal and abnormal biologic processes and also for the need for valid substantive questions to which these technologies can be applied. Given the inherent bias of the group it was agreed that the focus should be disease specific rather than normal functions and focus on the integration of different components of a single disease, e.g. Crohn's disease, using a systems biology approach. Biomarker development was identified as one area that would benefit from an integrated approach and could also make use of existing resources such as the Manitoba prospective cohort study of patients with Crohn's disease.
It was agreed that all the clinical autoimmunity teams could benefit from systems biology expertise and if it were available from a core consultative resource they would definitely take advantage of it by recruiting experts/consultants for each team. This generated a debate on the dichotomy between a "user" and a "producer" approach. Rather than establish a central core of systems biology expertise, some researchers felt strongly that systems biology is an experimental science, still in need of development in most areas. An integrated team approach, therefore, would be most beneficial, where systems biologists and immunologists work together from the outset in tackling definedresearch questions.
In a situation of limited financial resources, the group felt that the development of a shared network of information from ongoing studies, (e.g. creation of a website) between teams and among other chronic disease groups would be valuable. With increased funding, the group favoured support of training programs and multidisciplinary team grants, and with substantial funding the group favoured the creation of a central bioinformatics core to address select projects through competition.
There was broad agreement that partnerships would be key, including industry partnerships with pharmaceutical companies and perhaps computer companies. It was also recommended that projects focus on one clinical problem initially, with a long term funding commitment to ensure growth and sustainability.
Group 3 - Immunology
Group 3 agreed with previous definitions of systems biology and identified vaccines, tolerance vs. non-tolerance, host pathogen interactions and chronic inflammatory/allergic disease as areas where a systems biology approach would be most beneficial. This group felt strongly that in addition to the challenges described by the other two groups, funding was perhaps the major challenge and that unless sufficient funds become available it might be better to do nothing at all rather than invest in small, insignificant projects. Emphasis was placed on the generation of meaningful partnerships between, for example, CIHR Institutes, Genome Canada, NRC, NSERC and industry. It was recommended that with sufficient funds (approximately $5 million per year) one or two major nodes could be established which would serve, to some extent at least, to overcome the geographical barriers Canadians experience in trying to create effective collaborations. It was also recognised that much could be learnt from the experiences of other countries, such as the US, Europe and Japan with respect to the kind of funding models best suited for a systems approach. Open access to datasets and other resources was also identified as a high priority.
Breakout Session 2 - Multidisciplinary
In this breakout session, participants were asked to put into practice what they had learnt during the presentations and discussions on the first day and design a research project that would integrate systems biology approaches with traditional immune modulation/inflammation research. Some key questions and suggested criteria were provided as a guide (Appendix 4). At the end of the breakout session, each group, presented their proposal to the entire group, which then voted (by show of hands) for the "best" proposal.
Group 1 - A Network Approach to Inflammatory Bowel Disease
Group 1 chose to focus on a single disease, IBD, because there is already an active research community, including teams funded under the III clinical autoimmunity initiative, there are existing cohorts (e.g. the Manitoba cohort), there is existing risk factor/genetic information, there are good animal models, and potential partners can easily be identified e.g. NGOs and industry.
The proposed project would aim to identify predictors of risk, onset, disease progression, patient subsets and outcome. The goal would be to identify new targets that could guide the use of existing therapies or lead to the development of new ones. The project would also study host-pathogen interactions in both normal individuals and patient sub sets (responders vs. non-responders).
The project would require the development of strong partnerships and a team environment that would bring together systems biologists, biologists and clinicians as equal partners to investigate a core problem. Training would by necessity be an integral part of the program and recruitment of a strong academic champion who could dedicate their time to leading and coordinating the project would be essential.
Experimentally, the project would require repeated cycles of proteomic, genetic and other analyses, development of models and testing relative to clinical data and mouse models in an iterative process. The project would build on existing national and international data and link appropriately. The project was envisaged as a large multi-centre team requiring in the range of $3-5 million per year for operation.
Group 2- Canadian Human Immunology and Systems Biology Initiative (CHISI)
Rather than an individual project, Group 2 designed an initiative to which research teams could apply though a competitive process based on either a centralized or distributed model. The initiative aligns with an NCE/Large Team grant model and requires a strong training component in which investigators could potentially have a 50% commitment to common shared projects and 50% to individual projects.
Successful applications would avoid redundancy and incorporate existing infrastructure and would have to include units in basic and clinical science, genomics, proteomics, computational biology, imaging, and technology development, etc. The end result would be one or more centralized or "virtual" institutes that would attract a new cadre of researchers and establish research teams able to generate and share new tools and resources in a systems biology approach to health research.
Again, partnership would be a key feature of the initiative with suggested partners including Genome Canada, CFI, the Provinces, charitable organizations, the NIH and the Canadian Microbiome Initiative. Funding in the region of $2-5 million would be required to establish and maintain each centre. Success would be measured by the generation of new knowledge, the forging of new alliances, an increase in the number of researchers taking a systems biology approach to health research, and knowledge transfer through technology development and commercialization.
Group 3 - A Systems Approach to Understanding the pathogenesis and developing treatment Options for Autoimmune Disease
Group 3's proposal followed an in depth discussion between the systems biologists and the immunologist/immunotherapists in the group and a comparison of the relative skills, expertise and approaches in both disciplines. The immunologists explained the complexity of disease pathogenesis and the fact that different autoimmune diseases don't necessarily share the same mechanisms, although it is hoped that commonalities can be found. From the biological perspective it is possible to collect data from blood and, in some cases, tissue samples, but it was not immediately clear how a systems biology approach could be integrated. From the systems biology perspective it is possible to obtain array studies in lymphocytes to get patterns of genes. If the assumption is made that it is the interaction networks in a cell that govern what happens and lead to genetic change, then by looking at gene expression data and hubs using algorithms, it is possible to make correlations to disease. Proteomic profiling is also possible and in animal models protein interactions can be mapped and localized. By working together it should be possible to match gene expression and protein interactions with disease processes and predict therapeutic outcomes. Outcomes in one autoimmune disease could then be studied in multiple diseases.
The group, therefore, proposed a partnership between systems biologists and immunologists that would build on research currently funded by CIHR (e.g. the clinical autoimmunity teams) and integrate expertise from other fields (e.g. economists, ethicists, epidemiologists). One of the outcomes would be the recruitment of patients into cohort studies to enable long term research projects. Suggested partners included industry, NGOs and the Immune Tolerance Network in the US. The project would be in the form of a large team grant, able to integrate different disciplines to enhance our understanding of disease pathogenesis. Funding levels and infrastructure requirements were not defined.
Summary
The workshop was successful in bringing immunologists, clinicians and systems biologists together, in an environment where they were encouraged to network and open the channels of communication that are essential to future collaboration. All groups reported having learnt from each other and there appeared to be a genuine interest in pursuing collaborative opportunities. By the end of the workshop there was little doubt that a systems biology approach to immune modulation could be highly beneficial to the fields of immunotherapy and inflammation and would likely lead to advances in our understanding of disease pathogenesis. All the representatives of the Clinical Autoimmunity teams showed a keen interest in working with systems biologists to advance their research. It was also clear, however, that integration of the two sciences would not happen overnight as the communication challenges are not insignificant.
Workshop participants proposed several mechanisms to facilitate the creation of effective collaborations, including a variety of potential training models, staged investment in capacity building e.g. through catalyst grants or career transition awards, and the creation of integrated teams which could be either centralized or dispersed (if dispersed frequent face-to-face meetings were highly recommended).
It was recommended that any systems biology initiative be long term and sustainable. As a result, any program created is likely to be resource intensive, e.g. $5 million per. year, as a minimum investment. Partnerships would be essential to support such an expensive initiative. One partnership model could be a multi-Institute approach in which several CIHR Institutes combine funds to launch an initiative to support the integration of systems biology with health research but with clearly identified research areas corresponding to the Institutes' mandates. Another approach could be to seek partnerships with ongoing initiatives in the US, such as the Immune Tolerance Network or the systems biology initiatives, described by Dr, Germain, that exist within the NIH, or with other organizations such as NGOs.
Next Steps
One of the consistent messages from the workshop was to be bold and innovative and to "think big". Participants were strongly in favour of a bold new initiative with unique features. However the structure of such an initiative was not clearly defined in the short time available at the meeting. As a first step, the workshop was successful in establishing constructive dialogue between diverse research groups and promoting the concept of collaborations. More discussion will be necessary to identify a specific research program or vehicle that will successfully integrate systems biology approaches into biologically-orientated research such as immunotherapy and inflammation.
There are already existing CIHR programs, described to participants during the workshop, which might be appropriate first steps for collaborative projects and that are open to applicants immediately. These include the CIHR Strategic Training in Health Research Program - LOI April 1, Operating Grants - Registration August 1 and March 15, and the Collaborative Health Research Program (a partnership between CIHR and NSERC) - LOI May 1. Workshop support is also available on a competitive basis, with intake of applications in February, June and October.
In terms of a specific Request for Applications launched by III or multiple CIHR Institutes, this will be the topic of discussion for the III Institute Advisory Board, and the Research and Knowledge Translation Committee at CIHR which brings together all 13 Institute Scientific Directors with senior management to discuss research planning and priorities. Certainly III remains committed to taking the lead in facilitating the integration of systems biology approaches into traditional health research and will actively pursue avenues likely to make this a reality.
III remains committed to taking the lead in facilitating the integration of systems biology approaches into traditional health research and will actively pursue avenues likely to make this a reality.