Introduction

The spectacular successes of the Human genome project and ensuing technological advancements have caused a radical transformation of the biological and medical sciences. This transformation manifests as a shift toward a more holistic approach to biology and the emergence of Systems Biology as a formal scientific discipline. Systems Biology strives to achieve a quantitative and predictive understanding of biological systems by integrating techniques and methods from traditionally disconnected fields. This enables novel research strategies that offer concrete chances for the advancement of science and technology. National and international industrial and academic stakeholders have recognized Systems Biology internationally as a key theme in 21st century bioscience. As such, the development of the field in Canada will benefit researchers, industries and the general public by advancing science and technology areas important for the Canadian economy and the health and well being of Canadians.

In this report , we provide an overview of Systems Biology, its potential socio-economic impact and the existing strengths that give Canada a unique opportunity to become a key contributor to innovation and development in this field. We also discuss the challenges facing Systems Biology in Canada and make recommendations on how address them. These recommendations are compatible with measures implemented in most other industrialized nations.

In brief, past investments in genomics, proteomics and bioinformatics have provided the technological capacity needed for Systems Biology to flourish in Canada. However, this capacity and opportunity is at risk of not being used optimally without investing in Systems Biology research and education. To ensure that Canadian industries remain competitive internationally and that Canadians continue to reap the socio-economic benefits of an internationally competitive biomedical research enterprise, Canada should make a dedicated and substantial long-term investment to nurture and develop a far-reaching and comprehensive Systems Biology research environment.

Systems Biolog: a working definition

Past investments in technology development have made it possible to systematically identify and characterize molecules and molecular interactions that define cellular pathways, tissues, organs and organisms. The combination of such systems-level experimentation and the use of quantitative and computational tools to integrate, visualize and analyse the resulting experimental data is termed Integrative or Systems Biology. The goal of this scientific approach is to obtain a quantitative and predictive understanding and solutions of fundamental biological problems based on dynamic relationships between genetic, molecular, cellular, physiological and environmental factors.

The need for integrative and systems-oriented approaches in science becomes clear when considering the Human Genome Project. The completion of this project was expected to rapidly accelerate the understanding of illnesses by identifying disease-causing gene variants. The problem is that simple gene variation cannot explain the basis of the most common serious illnesses, such as cancer, heart disease, diabetes, asthma, and neurodegenerative disease, which arise from accumulative effects on cellular and organismal physiology of multiple gene variations and environmental factors. Consequently, the systematic sequencing of the genome, or any other characterization at a singular biological level, is unlikely to uncover causes and cures of many complex diseases. To achieve these goals it will be necessary to obtain, integrate and analyze biological data spanning multiple biological levels. Combining these three steps into one scientific strategy is the essence of Systems Biology research.

A key component in Systems Biology is the use of modelling and computational tools for data analysis, system simulation and hypothesis generation . This use of quantitative methods has been successful employed in many biological and biomedical research areas, including epidemiology, pharmacology, physiology, neuroscience and ecology. An initial emphasis of Systems Biology is to implement analogous approaches in molecular and cellular biology where the capacity for generating genomics and proteomics data is well developed and the potential for short-term success is greatest. However, the progression of the field will ultimately enable more accurate simulations and descriptions of more complex biological systems, including human physiology and disease. With appropriate levels of abstraction, these models will span all levels of biological organisation, from genes and molecular pathways, to cells, organs, organisms and ecosystems.

Systems Biology and society

The emergence of a scientific discipline can have enormous and lasting societal impact. For example, the establishment of Molecular Biology in the late 1930’s led to the discovery of the structure of DNA in the 1950’s, Genetic Engineering in the 1970’s, and the introduction of Genomics and Bioinformatics in the 1990’s. In addition to radically changing our understanding of life and humanity, these scientific milestones dramatically transformed the biological, biomedical and health sciences and laid the foundation for the development of new industrial sectors that are generating global revenues measured in trillions of dollars. The development of Systems Biology, which represents a natural next step in this chain of scientific advancements, is similarly expected to have a significant and lasting impact on society. The field offers concrete changes for success in facilitating advancements in areas that are important to the Canadian economy and to the health and well being of Canadians. Below we provide a brief summation of key areas where Systems Biology is expected to have the greatest impact. Additional details can be found in market analysis reports issued on this topic.

Figure 1. Examples of industrial applications of Systems Biology. Source: The Future of Systems Biology: Emerging technologies and their impact on drug discovery, development and diagnostics.

Economy: Systems Biology has broad applicability in industry (Figure 1) and the potential of applying Systems Biology methods to advance economic growth is widely accepted in industry (see Appendix I). The projected biological information technology (Bio-IT) market is $38 billion , with revenues from Systems Biology products and services expected to grow at an annual compound rate of 66% to $785 million by 2008.

In the pharmaceutical industry, Systems Biology is used among others to improve decision making during development and to identify targets during drug discovery . For example, F. Hoffmann-La Roche uses in silico technologies in approximately 50% of its projects, mostly drugs in Phase II and Phase III clinical trials . Companies in the pharmaceutical sector are also investing directly in the development of academic Systems Biology research. For example, Novartis and AstraZeneca sponsor Systems Biology professorships at Harvard University and the University of Cambridge, respectively. In Canada, Merck-Frosst is funding Systems Biology-related research on Alzheimer’s disease and Invitrogen is, among others, a scientific partner of the Canada-led International Regulome Consortium (IRC) focussing on the Systems Biology of transcriptional regulatory networks. Additionally, recent years have seen the emergence of numerous small and mid-sized Bio-IT companies commercializing Systems Biology. These companies offer technology solutions for data integration and visualization, as well as in silico simulations of pathways, cells, organs and whole-body systems. An example of a mid-sized Canadian company operating in this market is Victoria-based GenoLogics , which provides computational tools that help life science and pharmaceutical labs to manage, integrate and analyze scientific data.

While the Bio-IT and pharmaceutical sectors are expected to dominate the Systems Biology market, the applications of Systems Biology extend further. Among others, the integration and incorporation of multi-scale biological data into bioprocess design, development, operation and optimization will benefit Canadian industries through reduced production cost. For example, the global ethanol production capacity was 24 billion litres in 2005. Increasing this capacity by merely one percent will result in tens of millions of dollars in profit. In the context of the fuel alcohol industry, researchers in Canada and abroad are turning to Systems Biology to alleviate the adverse effects resulting form inhibition of ethanol synthesis under industrial conditions. Moreover, the future competitiveness in the global economy of the Canadian agri-food industry, which is the country’s third largest employer and generates roughly $100 billion in sales and retail activity annually, depends heavily on improving the yield and performance of major crops as well as developing new traits in crops . Similar to the trends in the fuel alcohol industry, agri-food researchers are increasingly relying on Systems Biology when developing metabolic and process-engineering strategies.

Health: The development of Systems Biology technology platforms capable of accurately predicting biological activities at the molecular, cellular and organ levels will have a direct impact on the development of new drugs as well as diagnostic and prognostic tools for the benefit of all Canadians. Additionally, by promoting a more comprehensive perspective on disease, Systems Biology will facilitate the development of new opportunities in medicine with respect to more dynamic and personalized treatment and prevention of disease . This can be realized by adapting Systems Biology tools in the analysis of complex health data to improve public health decisions . For example, many otherwise effective drugs are currently unavailable because of a few cases of adverse side effects that, in theory, could be predicted using Systems Biology tools. In other words, Systems Biology-based personalized medicine could assist in identifying individuals with predisposition for adverse side effects and thus increase the number of available drugs and treatment options for patient groups without these predispositions.

Another research area important to human health is environmental science. The environmental problems facing our society are so complex that it will require an integrated and interdisciplinary approach to address them. Consequently, many environmental scientists are now applying Systems Biology approaches in their research. This includes the development of tools to predict damage to organisms and ecosystems caused by exposure to environmental contaminants; to recognize early warning signs of ecosystem stress and damage; and the development of strategies for waste-site cleanup and bioremediation. Additionally, Systems Biology is being used to study the impact of man-made pollutants in the atmosphere on respiratory health, and to develop methods for the detection and mitigation of outbreaks caused by naturally or intentionally released biological agents such as anthrax, bird flu, and bovine spongiform encephalopathy (mad-cow disease).

Canadian strengths and challenges

Canada is in a uniquely favourable position to be a major international player in Systems Biology due to investments in building cutting-edge research capacity by the Federal Government (i.e., Genome Canada, the Canada Research Chairs program and the Canadian Foundation for Innovation), as well as the Provincial Governments and most medical, academic and governmental research institutions. Because of these investments, Canada excels in some of the key experimental technologies fuelling Systems Biology. Canada also has significant capacity in relevant areas of computer science and engineering and has recently significantly bolstered its capacity in bioinformatics, computational, theoretical and mathematical biology by aggressive hiring of international experts in these fields. Nevertheless, despite availability of core technological and intellectual capacity, Systems Biology is underdeveloped in Canada.

There are several factors that impede the development of Systems Biology in Canada. Three specific challenges should be addressed for Systems Biology research in Canada to achieve its full potential and to ensure optimal use of capacity generated by past investments:

• Systems Biology projects often require a combination of funding-intensive high-throughput experimentation across multiple technology platforms and substantial expertise in data management, integration and analysis. Such projects are difficult to establish and maintain in the current funding environment. Specifically, the operational funding dedicated to interdisciplinary and integrative biological research is limited and existing grant panels are not designed to evaluate Systems Biology applications. Moreover, Genome Canada, which presently funds several Systems Biology and Systems Biology-related projects, only supports large-scale projects and is funded by a mechanism that is not clearly sustainable.
• Communication across the boundaries of scientific disciplines represents a serious obstacle to the future success of Systems Biology in Canada. Particularly, mathematical, statistical and computational modelling and analysis is vitally important for Systems Biology. The absence of quantitative methodologies in biological and biomedical training curricula makes it a challenge to establish interdisciplinary interactions and collaborations, particularly across the interfaces between science and medicine and between experiments and theory.
• The training of highly qualified Systems Biology personnel is virtually non-existent. As discussed in a recent Special Feature in Science magazine devoted to careers in Systems Biology , traditional training programs are not ideal for the education and training of highly qualified personnel with expertise in Systems Biology. This is also true in Canada. The existing research environments are not able to train a sufficient number of highly qualified personnel with the broad skill base required to meet the present and anticipated future demand within Canada and for Canada to compete internationally in Systems Biology research.

Facing the Systems Biology challenge

The development of Systems Biology in Canada will require adaptation to a new scientific reality at multiple levels. It is clear that the biosciences have entered an era where researchers with different expertises must work in close collaboration to address increasingly complex biological, technological and medical problems. Researchers, institutions and federal and provincial governments should take concrete steps to ensure that the Canadian public and economy benefit optimally from this new opportunity by facilitating and promoting the transition of Canadian research into the Systems Biology era.

Researchers should actively acquire the knowledge outside of their field of specialty required to efficiently exchange ideas with experts from other disciplines. To assist researchers in addressing this challenge, for example through workshops, site visits and exchange programs, the formative process for establishing a Canadian Society for Systems Biology was initiated by the scientific community in late 2005.

Institutions and provincial governments should actively promote and encourage interdisciplinary and collaborative research endeavours and educational programs. This integration and migration of scientific knowledge is a cornerstone in the formation of cohesive Systems Biology research groups, centres and institutes. A paradigmatic shift in education due to the new scientific reality will continue to affect virtually all biological and biomedical disciplines. There is a clear need for developing integrated cross-disciplinary educational programs. Substantial commitments should be made specifically for Systems Biology in terms of capital investments that can bring scientists from different disciplines together, and in the development of frameworks for resource management and interdisciplinary education. Additionally, research institutions should encourage and support Systems Biology research by developing clear career paths and opportunities in collaborative and integrative science.

The Government of Canada should implement appropriate measures to support Systems Biology research and education. To bring Canada to an internationally competitive level, the Canadian funding agencies and the Government of Canada should provide new funding in four key areas:

• The characterisation of the components, the interactions and the dynamics of complex biological systems through genome- and systems-scale analysis and experimentation.
• The development of accessible Systems Biology technology platforms, including technologies for automated high throughput and quantitative experimentation, cross-platform data integration and analysis, and systems-level simulations.
• The exploration and elucidation of the fundamental principles that govern information processing and dynamics at different levels of biological organization and across their boundaries.
• The education and training of highly qualified personnel to enhance the capacity for innovation in academia and industry, and provide the next generation of Systems Biology researchers.

Because faculty development and capital investments in these areas depend on institutional priorities, there is a clear need for institutional incentives to engage in long-term initiatives. A strong commitment in terms of operational funding from the Government of Canada could provide such an incentive and catalyse institutional and provisional prioritization in Systems Biology.

Recommendations

A determined and significant commitment to Systems Biology is required for Canada to maintain and improve its competitiveness in science and technology innovation and to build capacity that can attract industrial investments. For this purpose, it is recommended that the Canadian funding agencies and the Government of Canada in collaboration with scientists should develop a new mechanism and funding envelope for Systems Biology. This funding envelope is needed to support a broad range of interdisciplinary research topics and for new educational initiatives to train the next generation of academic, medical and industry researchers.

The establishment of a comprehensive and world-leading Systems Biology research environment in Canada will require an estimated $100 million in new annual operating funding with $20 million being awarded annually (Table 1). This funding should fuel the capacity generated by past investments, and ensure the sustainability of a core constituency of scientists. The estimated envelope is quite substantial; we note that this funding must not detract from increased and sustained funding for the Federal Granting Councils (CIHR, NSERC, SSHRC), since these agencies provide the essential foundation for all strategic research initiatives in Canada. The size of the program reflects the need for large-scale systematic experimentation (see below), which requires larger than normal operational funding. The benefit is that such data, when made publicly available, provides an invaluable and lasting research tool for the scientific community and an ongoing source of intellectual property and knowledge generation.

The proposed envelope should award funding on a peer-reviewed competitive basis in four categories:

• Team grants in the range of $2-10 million annually to support clearly integrated groups conducting collaborative systems-level and integrative research on a biological problem of particular importance to the economy or health. The research supported in this category would involve systematic high-throughput experimentation across multiple levels, the integration and analysis of the generated data as well as mathematical, statistical and computational modelling. The generated data should be accessible to the general scientific community.
• Operating grants up to $2 million annually to support research by individual and smaller groups of investigators. A portion of the research supported in this category would be similar to that supported in the Team grant category but at a smaller scale. Additionally, the Operating grant category would support interdisciplinary Systems Biology research by smaller interdisciplinary groups and individuals .
• Training grants to support graduate and post-graduate education and programs. To encourage collaboration between industry and academia, this category could also include funding for industry internships, temporary positions for industry-based researchers, as well as commercialization and technology transfer workshops.
• Short-term high-risk grants for new technology development or the launch new initiatives with the potential of being funded in the Team or the Operating grant category within two to three years.

The new operational resources are envisioned to fund innovative research groups and projects that will promote and foster Canadian Systems Biology in areas that have the greatest potential (see Appendix III). Again, it must be emphasized that this funding is not at the exclusion of normal increases to existing funding programs. A strong base in the traditional disciplines is crucial for the sustainability of Systems Biology. However, the program should support both basic and applied research. While the promise of Systems Biology will be realized short-term by applying existing technology platforms, further developments in basic research and instrumentation is needed to foster scientific advancements with long-term impact.

Initiatives supported by the proposed program should be awarded solely on scientific merit. Requiring fund matching or industrial co-sponsorship would negatively impact the international competitiveness of Canadian Systems Biology as funding mechanisms have been implemented abroad without such restrictions. Moreover, future commercial innovation and success in the biotechnology and health sectors will require the development of a strong academic basis in Systems Biology. Investing in Systems Biology in an academic context will provide Canada with the know-how and intellectual property that will facilitate the emergence of new companies, as well foster regional clusters of expertise that can attract industrial investments. Industrial partnerships and the potential for commercialization should be considered when a scientific review panel evaluates the societal impact of a proposed project.

To foster a true integration of the physical and applied sciences with life and medical sciences, it is recommended that the new funding envelope be administered through collaboration between CIHR and NSERC. Dual-agency involvement is needed because the funding administration and the peer-review panels for Systems Biology should reflect and be able to evaluate the highly interdisciplinary research envisioned to be funded. Systems Biology is also a logical research area for future investment by Genome Canada, since initiatives are likely to evolve from capacities put in place by this agency.

Outlook

Systems Biology has been broadly accepted internationally as the next wave in the evolution of the biosciences. This emerging scientific field will be a key component of innovation and development in 21st century biotechnology and biomedicine. The novelty, strength and potential of Systems Biology comes from the integration of concepts and methodologies from traditionally disconnected fields. As such, Systems Biology can be viewed as an approach that expands on existing research capacity by providing researchers with new tools and strategies to address biological and medical questions of fundamental importance. The complexity of the important biological and medical problems facing our society requires interdisciplinary research and the coordinated expertise of multidisciplinary teams where biologists and clinicians are engaged in collaborative work with experts from other disciplines. The successful creation of such teams across Canada, together with the necessary support infrastructure and teaching facilities is one of the proposed program’s most important first goals and successful early outcomes.

Significant investments have already been made worldwide to develop Systems Biology in both academic and industrial contexts. The absence of support in Canada that can compare to that seen in other countries puts Canada and Canadian industries at serious risk in terms of international competitiveness. Moreover, without new operational funding for Systems Biology research, there is a real possibility that the full benefits of the substantial past investments in research capacity and technology will not be realized. These investments have placed Canada in a unique position to take advantage of the opportunities offered by Systems Biology - this is the right time, and Canada is the right place, for Systems Biology to flourish. Investments dedicated to interdisciplinary Systems Biology research and education will ensure that Canada maintains a leading role in science and technology innovation, and that Canadian bioscience and biotechnology sectors can improve and maintain competitiveness internationally.

Contributing Authors

This report is the outcome of the “Organisational Meeting for Systems Biology in Canada” held at University of Toronto’s Terrence Donnelly Centre for Cellular & Biomolecular Research in February 2006, and subsequent discussions with representative scientists. 

Workshop participants

• Brenda Andrews (co-organiser). University of Toronto
• Eldon Emberly. Simon Fraser University
• Daniel Figeys (co-organiser). University of Ottawa
• Michael Hallett. McGill University
• Philip Hieter. University of British Columbia
• Brian Ingalls. University of Waterloo
• Mads Kaern (co-organiser). University of Ottawa
• Stuart Kauffman (co-organiser). University of Calgary
• John Parkinson. University of Toronto
• Anthony Pawson. University of Toronto
• Michael Surette. University of Calgary
• Peter Swain. McGill University
• Shoshanna Wodak. University of Toronto

Representative Scientists

• Gabrielle Adams. National Research Council
• John Aitchison. Seattle Institute of Systems Biology
• Miguel Andrade. University of Ottawa
• Prabhat Arya. National Research Council
• Wolfgang Banzhaf. Memorial University of Newfoundland
• John Bate. University of Manitoba
• Kristin Baetz. University of Ottawa
• David Baillie. Simon Fraser University
• John Bergeron McGill University
• Joseph Bielawksi. Dalhousie University
• Mathieu Blanchette. McGill University
• Hamid Bolouri. Seattle Institute of Systems Biology
• Charlie Boone. University of Toronto
• Michel Bouvier. Université de Montréal
• Jean-Robert Brisson. National Research Council
• Eric Brown. McMaster University
• Gertraud Burger. Université de Montréal
• Trevor Charles. University of Waterloo
• Pierre Chartrand. Université de Montréal
• Eric Chevet. McGill University
• Michel Chrétien. University of Ottawa
• Benoit Coulombe. Inst. de recherches cliniques de Montréal
• Miroslava Cuperlovic-Culf. Beausejour Med. Research Inst.
• Eric Cytrynbaum. University of British Columbia
• Robert Davidson. Global Consortia, Invitrogen
• Michel Dumontier. Carleton University
• Bernard Duncker. University of Waterloo
• Roshni Dutton. BioProcess Assist Ltd.
• Leah Edelstein-Keshet. University of British Columbia
• Marc Ekker. University of Ottawa
• Andrew Emili. University of Toronto
• Abolfazl Famili. National Research Council.
• Marvin Fritzler. University of Calgary
• Leon Glass. McGill University
• Richard Gordon. University of Manitoba
• Abba Gumel. University of Manitoba
• Arvind Gupta. Simon Fraser University
• Manish Kumar Gupta. Queen’s University
• Robert Hache. University of Ottawa
• Christina K. Haston. McGill University
• Geoff Hicks. University of Manitoba
• Tim Hughes. University of Toronto
• Pablo Iglesias. John Hopkins University
• Sarah Jenna. McGill University
• Mario Jolicoeur. École Polytechnique de Montréal
• Igor Jurisica. Ontario Cancer Institute
• Steven Jones. BC Cancer Research Centre
• Rob Kearney. McGill University
• John Kelly. National Research Council
• Martin Latterich. McGill University
• Ming Li. University of Waterloo
• Yen-Han Lin. University of Saskatchewan
• Michael Mackey. McGill University
• Len Maler. University of Ottawa
• Francois Major. Université de Montréal
• Brendan McConkey. University of Waterloo
• Tarik Möröy. Institut de recherches cliniques de Montréal
• Francis Ouellette. University of British Columbia
• Rodney Ouellette. Beausejour Medical Research Institute
• Chris Overall. University of British Columbia
• Morag Park. McGill University
• Theodore Perkins. McGill University
• Michel Perrier. École Polytechnique de Montréal
• Guy Poirier. Université Laval
• Jim Richards. National Research Council
• François Robert. Inst. de recherches cliniques de Montréal
• Andrew Roger. Dalhousie University
• Michael Rudnicki. University of Ottawa
• Waheed Sangrar. Queen’s University
• Gordon Shore. McGill University
• Danica Stanimirovic. National Research Council
• Ed Susko. Dalhousie University
• Elisabeth Tillier. University of Toronto
• David Thomas. McGill University
• Pierre Thibault. Université de Montréal
• Michel Tremblay. McGill University
• Jack Tusynki. University of Alberta
• Mike Tyers. University of Toronto
• Roy Walker. National Research Council
• Edwin Wang. National Research Council
• John Wilkins. University of Manitoba
• Gerry Wright. McMaster University
• Xihua Xia. University of Ottawa

Appendix I: Systems Biology in industry

The potential of Systems Biology for advancing innovation in biomedical applications, medical instrumentation and bio-information technology have been recognized broadly in industry. For example, one of the world’s leading pharmaceutical companies, Eli Lilly and Company, has established Lilly Systems Biology in Singapore. Additionally, GlaxoSmithKline has invested directly in Systems Biology through its Scientific Computing and Mathematical Modelling Group. Merck has established an Applied Computer and Mathematics Department and is funding theoretical work on Alzheimer’s disease in Canada . Novartis is viewing Systems Biology as a necessary next step in drug discovery and sponsors a Professorship of Systems Biology at Harvard Medical School. AstraZeneca is employing Systems Biology methodologies in their Pathway Analysis Program and is supporting a Senior Research Associateship in Systems Biology at the University of Cambridge.

In addition to investments by larger international corporations, numerous emergent biotech and Bio-IT companies, including BG Medicine, BioSeek, CellZome AG, Entelos, Genomatica, Gene Network Sciences, GeneGo, Genstruct, Incora, InSilico Biosciences, Panomics and Optimata have been founded based on Systems Biology technology platforms that are used primarily in drug discovery and in the development of products for medical and industrial biotechnology. The industrial aspects of Systems Biology, current market trends, emergent companies and future potential is further described and discussed in Bio-IT World’s Briefing on Systems Biology (available from www.bio-itworld.com), and in two reports: Systems Biology - Key to unlocking the value within the omics revolution by Drug & Market Development Publications and The Future of Systems Biology: Emerging technologies and their impact on drug discovery, development and diagnostics by Business Insights (both are available to purchase at www.researchandmarkets.com).

Appendix II: Systems Biology internationally

The United States, Japan, the United Kingdom, Switzerland and the countries of the European Union have all implemented mechanisms to fund Systems Biology research with United States and Japan being viewed as most progressive due to the early recognition of the field and substantial early investments. In fact, initiatives launched in the United States and in Japan are viewed as the main thrust behind the emergence of Systems Biology as a formal discipline. Central milestones include the founding in the US of the Molecular Sciences Institute in 1996 and the Institute of Systems Biology in 2000, and the launch in Japan of the E-Cell Project in 1996 and the Kitano Symbiotic Systems Project in 1998.

In order to recognize the context in which Canadian Systems Biology has to operate and compete, the sections below provide brief summaries of some of the major System Biology and Systems Biology-related initiatives in the United States and selected European countries. It is noted that the review is not exhaustive and only highlights a few of the most representative initiatives. Additional information is provided by Science magazine and the World Technology Evaluation Centre.

The United States of America

The US government has made massive investments to establish, develop and sustain systems-oriented and integrative research, and the major universities have made substantial commitments. For example, Harvard University has established a Department of Systems Biology , its first new academic unit in 40 years, with is own Ph.D. program and an expected size of 20-25 faculty members. Other noticeable interdisciplinary centres include the NIH-funded Institute of Systems Biology in Seattle, the Computational and Systems Biology Initiative at the Massachusetts Institute of Technology , the Bio-X program at Stanford University and the Center for Quantitative Biology at Princeton University . In addition, the Broad Institute, which is a research collaboration of the Massachusetts Institute of Technology, Harvard University and its affiliated hospitals and the Whitehead Institute, was founded to bridge the gap between genomics and medicine by hosting scientific programs in diverse areas such as Cancer, Medical and Population Genetics, Genome Biology and Cell Circuits, Chemical Biology, Metabolic Disease as well as Computational Biology and Bioinformatics. These and other initiatives are supported through programs launched by the National Institutes of Health, the National Science Foundation, the Department of Defence, the Army Research Office, and the Department of Energy.

The National Institutes of Health (NIH) has a Roadmap for Medical Research that contains several Systems Biology-related strategic areas of development, including the US$300 million Molecular Libraries Initiative, which includes the NIH Chemical Genomics Center, a national network of molecular screening centres, and the development and expansion of computational and predictive modelling. The NIH is in this context supporting seven Roadmap National Centers for Biomedical Computing . The National Institute of General Medical Sciences (NIGMS) has a dedicated Systems Biology Initiative that funds centres, research projects and education programs. The specific objective of the initiative is to attract investigators trained in the mathematically based disciplines to the study of biomedical problems. The NIGMS currently supports centres at Case Western Reserve University, Harvard University, Massachusetts Institute of Technology, Princeton University and the University of Washington. Additionally, the National Heart, Lung, and Blood Institute has currently an open Request for Applications to apply Systems Biology approaches to innovative, high-risk, high-impact research by multidisciplinary teams of investigators.

The National Science Foundation has an Integrative Organismal Biology program that supports research aimed at integrative understanding, through advanced computational techniques and interdisciplinary perspectives, from the molecular through the ecosystem levels.

The Defence Advanced Research Projects Agency (DARPA) under the Department of Defence (DOD) has supported Systems Biology research, including $5.3 million US for Stanford’s Bio-X program and two computational technology platforms, the Systems Biology Mark-up Language and the Bio-Spice software , for the simulation of complex biological systems.

The Army Research Office is funding Systems Biology-related biotechnology development through, for example, its five-year US$50 million award to the establishment of the Institute of Collaborative Biotechnology as a partnership between University of California, Santa Barbara, the Massachusetts Institute of Technology, the California Institute of Technology and six industrial partners that will develop the technologies created in the university laboratories.

The Department of Energy (DOE) launched a major Systems Biology initiative, the Genomics: GTL (Genomes to Life) program, in 2002 . The initial phase of the 25-year program seeks to facilitate and accelerate the transition from genomics to Systems Biology with an emphasis on microbiology. It sponsors seven major research initiatives, three Institutes for the Advancement of Computational Biology Research & Education as well as principal investigator-based projects. The DOE budget for 2007 includes roughly $160 million for the Genomics: GTL program . It is interesting to note this is significantly higher than that requested for the Human Genome project, highlighting the seriousness of the commitment to develop Systems Biology.

Europe

A recent European Science Foundation Policy Briefing outlined several national and trans-national Systems Biology funding programs recently launched in European Union member states. Most European countries have long traditions of Systems Biology-related research and have numerous local clusters of expertise that are gradually evolving into Systems Biology groups and centres. The sections below provide a brief description of some of the national Systems Biology initiatives in Germany, Switzerland and the United Kingdom as well as pan-European projects supported by the European Commission. Additional noteworthy initiatives include the $3.7 million Systems Biology initiative at the Hamilton Institute in Ireland , and the French Agence Nationale de la Recherche new funding program “Biologie Systémique (BIOSYS)”, which had its first call for applications in February 2006.

Germany is among the leading European Systems Biology nations and has made substantial investments and commitments. For example, the Federal German Government has a “Systems to Life – Systems Biology” funding priority program , and has committed $152 million to a Systems Biology project studying the liver.

Switzerland supports Systems Biology through initiatives such as the SystemsX program founded by ETH Zurich, University of Basel and University of Zurich. The initiative, which is funded by pharmaceutical giant F. Hoffmann-La Roche (Roche), receives support amounting to $8.7 million from the Swiss Federal Institute of Technology in 2006 and 2007. An additional $17.4 million is provided by the local government to construct a new Center of Biosystems and Engineering in Basel . Additionally, the Department of Biology at the ETH Zurich founded the Institute of Molecular Systems Biology in 2005.

The United Kingdom provides direct support for Centres for Integrative and Systems Biology through the Biotechnology and Biological Sciences Research Council. These centres are intended to possess the vision, breadth of intellectual leadership and research resources to integrate traditionally separate disciplines, such as biology, chemistry, computer science, engineering, mathematics and physics, into quantitative and predictive Systems Biology programs. Each centre may request up to $14 million with an additional $3 million dedicated to the building of multidisciplinary teams through the engagement of physical scientists and mathematicians.

The European Commission is providing strong support for Integrative and Systems Biology that augments the national initiatives. Examples of Systems Biology-oriented transnational funding and research programs supported by the European Commission are EUSYSBIO, focusing on the training of young scientists and international networking; ERASysBio, a long-term initiative to coordinate research activities and to create a European Research Area for Systems Biology ; the Yeast Systems Biology Network, which uses yeast as a model system to study the rules governing the dynamic operation of cellular systems ; BIOSIM, a Network of Excellence for the development and use of simulation techniques ; QUASI, a program employing multidisciplinary approaches to decipher basic mechanisms underlying signal transduction, intracellular communication and transcriptional activation ; COMBIO, aiming at bringing computational biology to the bench through an integrative approach to cellular signalling and control processes ; EMI-CD, a modelling initiative for the development of software platforms for combating complex diseases ; and the COSBICS program aiming to establish and apply a novel computational framework in which to investigate dynamic interactions of molecules within cells.

Appendix III: Assessment of Systems Biology potential in Canada

While a national Systems Biology funding strategy is yet to be developed, Canadian researchers have been active in launching Systems Biology-related initiatives both nationally and internationally. An example of international leadership in Systems Biology is the Canada-led International Regulome Consortium (IRC). Noticeably, the Canadian component of the IRC, in contrast to the international partners, the Welcome Trust Sanger Institute, the Erasmus Medical Center and Genomics Institute of Singapore and other research institutions in continental Europe and Australia, has yet to secure funding. In addition, investments made through the Genome Canada program have created significant Systems Biology-related research capacity, particularly in infrastructure supporting genomics and proteomics research. If utilized appropriately, this infrastructure provides Canada with the potential to become one of the world-leading Systems Biology nations. In the sections below, we provide further evidence for the potential of Systems Biology in Canada by highlighting exiting initiatives across the country.

Atlantic Canada has several initiatives under development to promote integrative and systems level understanding of biological phenomena and biomedical conditions. The North Atlantic Resource for Molecular, Cellular, Integrative and Network Sciences (NARIS) is expected to provide a major addition to high-throughput experimental and computational capacity in Newfoundland, and act as a hub for Systems Biology-related research in this region. Additionally, Dalhousie University recently started a graduate program in Bioinformatics and Computational Biology based on a tradition of strength in the area of evolutionary biology. Dalhousie researchers are spear-heading one of this countries oldest interdisciplinary Systems Biology-related initiatives, the Canadian Institute of Advanced Research’s program in Evolutionary Biology, which aims at providing new understanding of organisms and ecosystems by combining molecular biology, genetics, population biology, bacteriology, protozoology, botany, zoology, chemistry, biochemistry, mathematics, and computer science.

Quebec has a long tradition of integrative and quantitative research and has held a strong international position for many years through the interdisciplinary, multi-university Centre for Nonlinear Dynamics in Physiology and Disease (CND) hosted by McGill University. The CND runs a summer school entitled “Systems Biology: from Genes to Organisms”. In addition to this international flagship for Systems Biology and interdisciplinary education, McGill University’s Department of Anatomy and Cell Biology will soon introduce a graduate track in Human Systems Biology. Moreover, the University of Montreal’s Institute for Research in Immunology and Cancer (IRIC) is starting a new graduate course in Systems Biology as a first step in setting up a new graduate training program, and the Institut de recherches cliniques de Montréal (IRCM) have made significant effort towards the implementation of Systems Biology as a new research theme. École Polytechnique de Montréal has also numerous Systems Biology-related initiatives in the areas of functional genomics, metabolomics and biological pathway analysis and the opening of a new Genomics Centre in Québec City is expected to accelerate the formation of a virtual Systems Biology group with participation from Montreal, Québec City and Sherbrooke. Additionally, Genome Québec has made significant investments to improve genomics and proteomics infrastructure through the McGill University and Genome Québec Innovation Centre, and is sponsoring Systems Biology-related research programs, such as, for example, the multi-university project “Regulatory Networks in Gene Expression: From the Genome to the Organism” and the “Montreal Network for Pharmaco-Proteomics and Structural Genomics”.

Ontario has several emerging Systems Biology-specific initiatives that include the establishment of the Centre of Cellular and Biomolecular Research at the University of Toronto to stimulate unconventional interactions among disciplines; the founding, by the University of Ottawa and the National Research Council, of the Ottawa Institute of Systems Biology; and the launch of a program in Integrated Systems Biology and of the Sun Centre of Excellence in Systems Biology at Mount Sinai Hospital's Samuel Lunenfeld Research Institute in Toronto. Additionally, the Centre for Computational Biology at Toronto’s Hospital for Sick Children is dedicated to the advancement of Systems Biology research. Another example of a Systems Biology-related initiative is University of Ottawa’s recently established Centre for Advanced Research in Environmental Genomics (CAREG), which seeks to integrate the fields of eco-toxicology, genetics, physiology and bioinformatics to develop novel genomics-based solutions to environmental problems. Genome Canada, through the Ontario Genomics Institute, has made significant investments in genomics and proteomics infrastructure as well as Systems Biology-related research programs such as the Stem Cell Genomics Project, the Biomolecular Interaction Network Database project, the Proteomics and Functional Genomics: An Integrated Approach program, and the Dynactome Project seeking to map spatio-temporal dynamic systems in humans.

The Prairie Provinces interdisciplinary include the Manitoba Centre for Proteomics and Systems Biology, dedicated to the promotion and practice of Systems Biology and Proteomics, and the Institute for Biocomplexity and Informatics at the University of Calgary, which, in collaboration with the Alberta Ingenuity Centre for Machine Learning, focuses on the structure, dynamics and evolution of genetic regulatory networks and their behaviours. In addition, the Institute for Biomolecular Design at the University of Alberta, which is an interdisciplinary research and platform technology centre, is an international contributor to in silico technology innovation through its Project CyberCell. Genome Prairie is also supporting Systems Biology-related research programs, such as the development of an integrated and distributed bioinformatics platform, and the Sun Centre of Excellence for Visual Genomics at the University of Calgary. In addition, the University of Manitoba’s Mammalian Functional Genomics program is involved in Systems Biology-related research, for example, through the Genome Canada funded NorCOMM project and the International Knockout Mouse Project. Genome Canada also supports the Human Metabolome Project at the University of Alberta.

British Columbia has a strong presence in Systems Biology through a formal affiliation of the world-leading Institute of Systems Biology in Seattle with the University of British Columbia. Significant existing strengths, particularly in genomics, proteomics, bioinformatics and mathematical biology, provide a solid foundation for further developments. For example, in proteomics, the University of British Columbia recently launched a new life science institute, the Canadian Laboratories in Integrated Proteolysis. Moreover, the nationally and internationally renowned Bioinformatics Training Program for Health Research, offered through a partnership between Simon Fraser University, the University of British Columbia, and the BC Cancer Agency, and the Canadian Genetic Disease Network’s Canadian Bioinformatics Workshop series housed at the bioinformatics.ca resource, which is the portal to bioinformatics activities in Canada, are some of the examples of the strong capacity and expertise in Systems Biology-related research. Additionally, the University of British Columbia has a pan-Canada program in Biomedical Models of Cellular and Physiological Systems and Disease, which is a full project under the auspices of the Mathematics of Information Technology and Complex Systems Network of Centres of Excellence housed at Simon Fraser University.

The National Research Council is traditionally strong in integrative multi-disciplinary research and technology development and transfer. Its investments through the Genomics and Health Initiative (GHI) have lead to a significant genomic and proteomic infrastructure in several regions across the country. The GHI, established in 1999 in order to bring the benefits of genome and health sciences to all Canadians, funds focused inter-disciplinary programs combining elements of genomics, proteomics, bioinformatics and convergence technologies to address health-related issues in a Systems Biology-related manner. Examples of NRC-based Systems Biology-related programs include Cancer Genomics; Genomics for Enhanced Crop Performance; Human Pathogens and their Host Interactions; and Systems Biology of Brain Cell Interactions. The NRC also has considerable expertise and strength in Information Technology and has developed a number of tools for data mining of large datasets and the integration of diverse datasets. Additionally, the program in Genomics-Based Approach to Enhancing Bioremediation through Microbial Identification and Community Profiling could provide a cornerstone for the development of Environmental Systems Biology in Canada. Innovation and expertise in instrumentation is critical for Systems Biology and the NRC could become an important partner in Canadian Systems Biology by developing and providing cutting-edge technology platforms and facilitating interactions among scientific and industry communities.