Canadian-German Collaboration on Infectious Disease Research

Meeting Report

Montreal, Quebec
Canada
November 6-7, 2006

Executive Summary
Background
Meeting Overview
Meeting Summary
- The German Research Environment
- The Canadian Research Environment
Strategic Research Priorities
- Emerging and Neglected Infectious Diseases and Zoonoses Strategic Research Priority
- Genetics of Susceptibility to Infection Strategic Research Priority
- Vaccine Development and Evaluation Strategic Research Priority
- Microbial Virulence and Antibiotic Resistance Strategic Research Priority
- Infections of "Abnormal" Hosts Strategic Research Priority
Organizations and Mechanisms to Facilitate Collaborations
Strategies for Moving Forward
Next Steps
Appendix 1: Organizing Committee
Appendix 2: Meeting Participants

Executive Summary

In 1971, the Canadian and German governments signed an agreement on scientific and technical cooperation with goals to both strengthen ties and broaden the scope of cooperation between the two countries. On November 6 and 7, 2006, the Canadian Institutes of Health Research (CIHR), the Helmholtz Centre for Infection Research and the Federal Ministry of Education and Research (BMBF) held a one-and-a-half day meeting in Montreal, Canada to facilitate collaborations in infectious disease research. The meeting brought together leading researchers along with representatives from both federal governments, as well as sponsoring agencies, and the working group on Canadian and German Scientific and Technical Cooperation. Participants shared information about infectious disease research in both countries, developed priorities in five strategic areas, and built a foundation for future collaboration.

Drs. Rudi Balling and Emil Skamene, co-chairs of the organizing committee, began the meeting with a review of the German and Canadian research environments in infectious disease. In both countries, a critical mass of individuals, laboratories and institutions focus on infectious disease research. This provides strength in bacteriology, virology, immunology, vaccine development, animal models and human and animal genetics in both countries.

Following the presentations by the meeting co-chairs, participants gathered together into small groups to develop strategic priorities for collaboration in five theme areas: emerging and neglected infectious diseases and zoonoses; genetics of susceptibility to infection; vaccine development and evaluation; microbial virulence and antibiotic resistance; and infections of 'abnormal' hosts. Priority was given to research that would have a major impact on human health and is feasible because research expertise and facilities exist in both countries. The strategic research priorities identified at the meeting were:

respiratory infectious diseases
genetics of susceptibility to respiratory infections
new strategies to safely vaccinate against mucosal pathogens
systems biology approaches to bacterial respiratory infections
definition of an immune phenotyping platform with standard procedures

Participants also identified organizations and mechanisms in order to support and foster collaboration. These included personnel and trainee exchanges, joint meetings and visits between researchers from both countries, sharing of reagents and expertise, and the formation of a centre of excellence. In addition, discussions amongst participants at the meeting held in Montreal are likely to be the basis of formal collaborations in the future.

The organizers and participants were very pleased with the constructive nature of the meeting and the degree of interest and cooperation that was evident. The identified research priorities and suggestions for organizations and mechanisms to support collaborations will foster in depth strategic discussions that will take place at the stage two meeting in Germany, which is scheduled for March 2007. The goal of the stage two meeting is to both discuss recommendations made at the Montreal meeting and plan specific actions.

Background

In 1971, the Canadian and German governments signed an agreement on scientific and technical cooperation. The goal of the agreement was to both strengthen ties and broaden the scope of scientific and technological cooperation between the two countries while recognizing the beneficial effects that such cooperation can have on the quality of life and economic well-being of their respective peoples.

Under this agreement, the Canadian Institutes of Health Research (CIHR), the Helmholtz Centre for Infection Research and Germany's Federal Ministry of Education and Research (or BMBF) hosted a meeting in Montreal on November 6 and 7, 2006 to facilitate collaborations in infectious disease. Participants included leading infectious disease researchers from both countries, representatives from sponsoring agencies, both federal governments and the working group on Canadian and German Scientific and Technical Cooperation. See Appendix 1 for the organizing committee members and Appendix 2 for a list of meeting participants.

Meeting Overview

The purpose of the meeting in Montreal was to identify key infectious disease issues of mutual interest, as well as recognize mechanisms and organizations that can enhance and build collaborations in these areas. The primary objectives were to:

build relationships and enhance linkages and interactions among leading German and Canadian researchers who are committed to innovation and excellence in addressing strategic issues in infectious disease research
share information and develop priorities in five strategic research theme areas:

emerging and neglected infectious diseases and zoonoses
genetics of susceptibility to infection
vaccine development and evaluation
microbial virulence and antibiotic resistance
infections of 'abnormal' hosts

develop the groundwork for future collaborations and a second meeting among leading German and Canadian infectious disease researchers.

Drs. Rudi Balling and Emil Skamene, co-chairs of the meeting organizing committee, set the stage for discussion with a review of the German and Canadian research environments in infectious disease. Participants then gathered in small groups based on the five theme areas, in order to identify strategic research priorities for collaboration between Germany and Canada in the assigned theme areas. The top research strategic priorities from each group were discussed in plenary and the priorities were refined. These priorities will form the basis of a stage two meeting, which is scheduled in Germany for March 2007.

Meeting Summary

The German Research Environment

Dr. Rudi Balling, Director
Helmholtz Centre for Infection Research
Many research organizations throughout Germany are engaged in infectious disease research. These include universities, the Max Planck Society (Max Planck Institute of Immunobiology and the Max Planck Institute for Infection Biology), the Leibniz Society (Bernhard Nocht Institute for Tropical Medicine, Research Center Borstel, Heinrich Pette Institute for Experimental Virology and Immunology and Hans Knöll Institute for Natural Compounds and Infection Biology), the Helmholtz Association (Helmholtz Centre for Infection Research) and the Fraunhofer Society. Germany also participates in several European research activities in infectious disease. Strengths in German infectious disease research include: basic research in infection and immunity, virology, immunology, immunotherapy and animal models, and the presence of several dedicated centres with a critical mass of researchers. Areas that require development include: clinical infectious disease, public health and infectious disease epidemiology research. The main research funding organizations in Germany are the German Research Foundation (DFG) and the Federal Ministry for Education and Research (BMBF), which both fund infectious disease research programs and initiatives. German researchers also receive funds from international organizations such as the Bill and Melinda Gates Foundation and, in a few cases, the National Institutes of Health (NIH).

The Canadian Research Environment

Dr. Emil Skamene, Professor of Medicine, Genetics and Immunology
McGill University
In Canada, research on infectious diseases is carried out at universities, research institutes, hospitals, and government organizations. Some examples are: Centre for Microbial Diseases and Immunology Research and the Vaccine Evaluation Centre at the University of British Columbia, the Vaccine and Infectious Disease Organization at the University of Saskatchewan, Centre for the Study of Host Resistance at McGill University and the National Microbiology Laboratory and the Canadian Science Centre for Human and Animal Health in Manitoba. Canada's strengths in infectious disease research include: antimicrobial resistance, molecular diagnostics, vaccine development, virulence mechanisms, emerging infectious diseases, HIV/AIDS, hepatitis C, influenza, tuberculosis, malaria and pathogenic E. coli. Canada also has strengths in research examining host responses including human and animal genetics, animal models, immunology, innate immunity and host-pathogen interaction. Areas in which gaps exist include clinical research, particularly clinical trials. The Canadian Institutes of Health Research (CIHR) is the main funding organization for health research at the federal level. Other federal funding organizations include the Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Foundation for Innovation (CFI), Genome Canada, Networks of Centres of Excellence, Canada Research Chairs (CRC), International Development Research Centre (IDRC) and Canadian International Development Agency (CIDA). Several provincial funding organizatons exist. Research is also funded by organizations dedicated to preventing and treating specific diseases and by international organizations.

Strategic Research Priorities

Participants were divided into small groups to discuss strategic priorities for collaboration in five research theme areas that are important for understanding, preventing and treating infectious diseases. Participants developed criteria for selection of research priorities:

there is research strength in both countries or complementary strengths in each country
the research will have an impact on human health
the research is feasible (i.e. the research is a 'realistic stretch', in that it pushes researchers in both countries to perform innovative and relevant research which can be accomplished)

As the meeting progressed, respiratory infectious diseases arose as a strategic priority for research collaboration between Germany and Canada. There were several reasons for this:

both countries have the research capacity and strength to study respiratory diseases at several levels. For example, Canada has developed research expertise in severe acute respiratory syndrome (SARS).
scientific and public concerns exist about a possible influenza pandemic that would affect both countries
both countries currently promote and support research to prepare for a potential influenza pandemic

Potential research collaborations between Canada and Germany could begin with research into influenza and expand to encompass other respiratory infectious diseases.

The final strategic priorities in each theme area are summarized below. The priorities partly reflect the expertise and research areas of the participants but the discussions, strategies and conclusions may benefit other areas for infectious disease research collaboration between the two countries.

Emerging and Neglected Infectious Diseases and Zoonoses

Strategic Research Priority: Respiratory Infectious Diseases

Respiratory infectious diseases are a serious human health concern and are potential emerging threats in both Germany and Canada. Respiratory diseases identified by the group included influenza, tuberculosis, and diseases caused by coronaviruses such as SARS. Both countries have the expertise and capacity to conduct research in this area.

Expert leads
Germany: Georg Herrler, Otto Haller, Christian Drosten
Canada: David Speert, Marcel Behr, Mark Loeb, Alison McGeer, Yan Li, Dick Menzies

Other research areas
Other priority areas that were identified are vector-borne diseases (e.g. West Nile virus, Lyme disease, etc.) and food- and water-borne diseases. Travel-related diseases, rapid diagnosis and control of emerging diseases and national preparedness were also discussed as potential areas for collaboration.

Genetics of Susceptibility to Infection

Strategic Research Priority: Genetics of Susceptibility to Respiratory Infections
Not all individuals respond in the same way to infection, and it would be ideal if we could understand the causes of these differences in order to optimally prevent and treat infectious diseases. Collaboration on this research priority could bridge mouse, veterinary and human studies. Genetically-altered mice would be useful in the effort to understand the genetics of human susceptibility to infections. Both countries have expertise in mouse genetics and immune phenotyping. Given that Canada is currently a member of the Infection and Immunity Consortium, its access to a source of novel mouse ENU-generated mutants would prove useful for these studies. The collaboration could also take a comparative biology approach in which humans and other animal models would be studied. Researchers in both countries could use these approaches to initially study influenza and then expand research to include a variety of infectious respiratory diseases and pathogens.

Expert leads
Germany: Klaus Schughart, Eva Medina, Andreas Lengeling, Rudi Balling
Canada: Philippe Gros (linkage to the Infection and Immunity Consortium), Emil Skamene

Other research areas
Other research areas discussed included studies that would bridge mouse and human genetics, septic shock in mice and humans as a model to forge collaboration, analysis of immune response/immune monitoring in mice and humans, and standardization of immune phenotyping.

Vaccine Development and Evaluation

Strategic Research Priority: New Strategies to Safely Vaccinate against Mucosal Pathogens
The aim of the collaboration would be to develop the necessary tools in order to understand the mechanisms of vaccine efficacy and failure and the host response after natural infections. Ultimately, this would optimize rationale human and veterinary vaccine design. Influenza and streptococcal species could be targeted initially and serve as models for future collaborations. In both countries, there is considerable expertise with adjuvants and formulations, as well as with animal models beyond the mouse. Combined, this will help researchers establish preclinical models with predictive value for humans that would aid in vaccine development.

Expert leads
Germany: Gerald Gerlach, Carlos Guzman
Canada: Andy Potter, Brian Ward

Other research areas
Related to the strategic research priority is the examination of vaccines and immune responses in the changing populations found in both countries (e.g.> during aging, in immigrants or in refugees). Evaluative modeling epidemiology and immune response monitoring, such as differentiating infected from vaccinated individuals, are other potential research areas that were discussed.

Microbial Virulence and Antibiotic Resistance

Strategic Research Priority: Systems Biology Approaches to Bacterial Respiratory Infections
Researchers in both Germany and Canada could also join forces in an effort to understand the role of inherent genetic variability in both the pathogen and the host and their interactions. The research would focus on understanding metabolic networks (e.g. bacterial physiology) using genomic and proteomic approaches such as examining gene/gene, protein/protein and protein/chemical interaction. Chemicals would include antibiotics and new chemicals from sources such as the environment. The approach requires expertise in bioinformatics, which both countries have (e.g. Germany and the European Molecular Biology Organization). The criteria identified for the selection of a model organism are:

a major worldwide health problem
a professional pathogen
genetically tractable
an issue of antibiotic resistance

Expert leads
Germany: Jurgen Heesemann, Tobias Welte, Susanne Haubler
Canada: Gerry Wright, Eric Brown

Other research areas
A more specific research area related to this strategic research priority involves developing novel approaches to drug discovery that will address the problems of microbial virulence and antibiotic resistance.

Infections of "Abnormal" Hosts

Strategic Research Priority: Definition of an Immune Phenotyping Platform with Standard Procedures
Both Germany and Canada have been developing and defining immune phenotyping platforms with standard procedures in their respective countries. The platforms extend beyond standard clinical immunology testing and involve systems biology approaches at the molecular and cellular level, including functional analysis, signalling and genetics. There is potential for both countries to collaborate in the transfer of complementary expertise, for example, through the exchange of personnel (both faculty and trainees). This collaborative platform could initially be used to study patients in both countries with primary immunodeficiencies in order to further understand the human immune system. This platform could also be adapted and used for many of the strategic research priorities identified at the meeting, such as understanding human susceptibility to infection or immune responses to vaccination.

Expert leads
Germany: Jan Buer, Bodo Grimbacher, Andreas Radbruch, Dirk Busch, Dolores Schendel, Stefan Meuer
Canada: David Speert, Chaim Roifman, Stuart Turvey

Other research areas
Another research priority for which there is considerable expertise is the determination of mechanisms that underline chronic persistent infection/inflammation in cystic fibrosis. This problem is very difficult to treat and severely complicates lung transplant operations. Another area for collaboration is human diseases using specific mouse models with mutations based upon genetic information from humans (e.g. single nucleotide changes rather than gene knock-outs).

Organizations and Mechanisms to Facilitate Collaborations

Organizations and mechanisms that could facilitate and support research collaborations between Germany and Canada were identified by participants when they formed small groups to discuss the five research themes. Many were applicable to all strategic priority areas, and there was some overlap, so all suggestions are grouped together below. A note is made when a suggestion applies to only one of the research priorities.

Funding organizations: Several organizations help support collaborative health research work between scientists. They include:
German
Canadian:
Others:
German and Canadian researchers could work together on joint requests for applications for seed money for projects in order to develop long-term funding opportunities.
Informal research collaborations formed by participants at the meeting in Montreal will likely lead to more formal collaborations in the future.
Further joint meetings amongst researchers in both countries should be encouraged. To this end, Dr. Rudi Balling invited Canadian participants to visit the Helmholtz Centre for Infection Research.
Collaborations could be set up to share knowledge, expertise, capacity and reagents. This could include maintaining valuable breeds/strains of animals in both countries to preserve valuable resources in the event of loss of the animals in one country.
Principal investigators and trainees should be involved in the collaborations. This could include co-supervision of trainees and trainee exchange.
Exchange of scientific expertise among Canadian and German health researchers could also include short- and long-term personnel exchanges. For example, European Union Special Support Actions (SSA) and Canadian Cystic Fibrosis Foundation (CCFF) could be approached for funding that would allow researchers to determine together the mechanisms underlying chronic persistent infection/inflammation in cystic fibrosis.
The possibility for an international alliance through the Helmholtz Association should be explored for all strategic research priorities.
Several groups suggested that a centre of excellence would be an ideal mechanism to foster German and Canadian research collaboration in a given research area. Canadian participants stated that the network could be modelled on the successful Canadian Bacterial Diseases Network Centres of Excellence (1988-2005). According to participants, this network was successful because of strong leadership and a willingness among members to work together and achieve common goals. If the focus on respiratory diseases were adopted, Dr. Rudi Balling suggested that the virtual network could be called the "Fire & Ice" Initiative. (Fighting Respiratory Infections-International Center of Excellence"). The vaccine development and evaluation theme group proposed a virtual Canadian-German Vaccine Institute engaged in the activities described in Figure 1.

Figure 1: Proposed structure and activities of the Canadian-German Vaccine Institute

Requirements for large research collaborations were identified. For example, these should have a management structure with shared and specific goals (vision and mission); advisory boards and independent oversight committees. Multidisciplinary or large teams would require project managers. Consortium agreements between institutions would also be required.

There should be clearly stated mechanisms of intellectual property management for all collaborations.

Strategies for Moving Forward

Recommendations were developed by participants to ensure that research collaborations between Germany and Canada in infectious disease are formed. Participants suggested that both Drs. Rudi Balling and Emil Skamene be re-appointed as organizing committee co-chairs to aid in the planning of the stage two meeting to be held in Germany. Drs. Balling and Skamene invited Canadian and German scientists to visit their respective countries in an effort to continue discussions. It was suggested that meeting participants and organizing committee members contact researchers who were not present at the meeting but named as expert leads to discuss the meeting outcomes and future collaborations. Communication among meeting participants was encouraged and a contact list was e-mailed to participants immediately after the meeting. Participants asked to be kept informed of future developments and plans for the stage two meeting in Germany. Germany will lead the planning of the stage two meeting. A schedule for the next stages in the collaboration should be developed as soon as possible.

Next Steps

The organizing committee was very pleased with the cooperative spirit of the participants and the constructive nature of the meeting. The identified research priorities and the suggestions for organizations and mechanisms to support research collaborations will form the basis of further strategic discussions that will take place at the stage two meeting in Germany. The goal of the stage two meeting, scheduled for March 2007, is to discuss specific actions and to implement recommendations made at the Montreal meeting. In the meantime, several activities are planned. With the goal of developing a collaborative research initiative, Drs. Bhagirath Singh and Peter Lange will discuss partnership opportunities that support influenza research in both Canada and Germany. Possible linkages to the CIHR Pandemic Preparedness Strategic Research Initiative will be explored. In addition, visits and discussions between German and Canadian researchers will take place before March to plan individual research collaborations.

Appendix 1: Organizing Committee

Co-chairs:

Rudi Balling, Helmholtz Centre for Infection Research
Emil Skamene, McGill University

Members:

Lorne Babiuk, University of Saskatchewan
John Carey, Canada-Germany Science and Technology Agreement
Abigail Forson, CIHR International Relations
Peter Lange, Canada-Germany Science and Technology Agreement
Carol Richardson, CIHR Institute of Infection and Immunity
Dolores Schendel, GSF - National Research Center for Environment and Health
Bhagirath Singh, CIHR Institute of Infection and Immunity

Appendix 2: Meeting Participants

Emerging and Neglected Infectious Diseases and Zoonoses
Facilitator	Bhagirath Singh, CIHR Institute of Infection and Immunity
Recorder	Carol Richardson, CIHR Institute of Infection and Immunity
Researchers	Harvey Artsob, Public Health Agency of Canada Marcel Behr, McGill University Health Centre Georg Herrler, University of Veterinary Medicine Hannover Achim Hoerauf, University Clinic Bonn
Genetics of Susceptibility to Infection
Facilitators	Rudi Balling, Helmholtz Centre for Infection Research Emil Skamene, McGill University
Recorder	Birgit Balster, Helmholtz Centre for Infection Research
Researchers	Keith Fowke, University of Manitoba Andreas Lengeling, Helmholtz Centre for Infection Research Erwin Schurr, McGill University Health Centre
Vaccine Development and Evaluation
Facilitator	Lorne Babiuk, University of Saskatchewan
Recorder	Michelle French, Scientific Communication
Researchers	Gerald Gerlach, University of Veterinary Medicine Hannover Carlos Guzman, Helmholtz Centre for Infection Research Andy Potter, University of Saskatchewan Brian Ward, McGill University Health Centre
Microbial Virulence and Antibiotic Resistance
Facilitator	John Carey, Canada-Germany Science and Technology Agreement
Recorder	Marianna Newkirk, McGill University Health Centre
Researchers	Eric Brown, McMaster University Julian Davies, University of British Columbia Regine Hakenbeck, University of Kaiserslautern, Department of Microbiology
Infections of "Abnormal" Hosts
Facilitator	Dolores Schendel, GSF - National Research Center for Environment and Health
Recorder	Abigail Forson, CIHR International Relations
Researchers	Jan Buer, Helmholtz Centre for Infection Research Susanne Haubler, Helmholtz Centre for Infection Research Joseph Lam, University of Guelph David Speert, University of British Columbia
Additional Attendees
Marcelo Gottschalk, Université de Montréal Peter Lange, Canada-Germany Science and Technology Agreement Henry Mantsch, Canadian Embassy in Berlin
Process Consultation and Facilitation
Strachan-Tomlinson, Ottawa, Canada
Report Writer
Michelle French, Scientific Communication

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