White Paper: The International Receptor Tyrosine Kinase Networks Consortium

VISION

The vision of the Consortium is to facilitate and coordinate international efforts to understand RTK signaling and its relationship to human pathologies. Experimental data derived from various diseases and tissue settings, as well as high-throughput experiments, will be combined into a shared database. The database will be used to build a constantly improving and expanding global model that will be supervised by the Consortium. Understanding mechanisms underlying RTK network function will provide breakthroughs in the diagnosis and treatment of major human diseases, lead to the design of new therapeutic drugs, and decrease the attrition rate of new drugs in development.

Because of the complexity of RTK networks, they can only be understood by rigorous and extensive experimental analyses of a limited number of well-defined experimental systems and equally rigorous and extensive mathematical analyses. The required mathematical and experimental expertise for understanding RTK networks cannot be found in any single laboratory or even country. Thus, the Consortium is dedicated to a strategy in which individual research groups can focus on their own area of excellence, and the data and models can be integrated at the community level. This requires a community infrastructure that can support distributed research. The Consortium will provide the standards that will allow multiple labs across the world to work together productively.

MISSION

The RTK Consortium is organized from a systems biology perspective to develop the framework necessary to understand RTK signaling networks central to major human pathologies and therapies. Systems biology is the study of living organisms in terms of their underlying network structure rather than simply their individual molecular components.

THE CONSORTIUM WILL

1. Produce and consolidate new and existing sets of unified experimental data relevant to building a systems-level model of RTK networks

2. Establish a universal computational framework for the collection, dissemination, and analysis of both data sets and models of RTK signaling networks.

The Consortium will foster cooperation between academia and industry to create predictive, systems-level models that can be used to develop therapies for human malignancies including cancer, immune-based disorders, inflammation, and diabetes. The Consortium will develop standards to 1) facilitate the comparison and integration of experimental data and modeling results between labs and industry groups worldwide, and 2) apply the most appropriate mathematical analyses to well-defined applications.

ORGANIZATION

The Consortium has been founded by premier modeling and experimental research groups from the USA, Japan, and Europe, and will operate globally. These groups have voluntarily committed to form a research consortium, share experimental data and emerging concepts in a timely way, and to make a substantive commitment to its success. Within the Consortium there will be an exchange of experimental data and mathematical models, as well as extensive sharing of human capital, protocols, reagents, and technologies. Large-scale experiments will be designed by both the computational and experimental groups. We expect that the mathematical analyses will be motivated by experimental and clinical groups with the aim of producing clinically relevant answers.

The Consortium will be managed by an executive committee and be assisted by an international advisory board. The ultimate control will be held by a council, which consists of the research leads of all participating groups.

FUNDING

Initial organizational efforts are being funded by the Riken Genomic Sciences Center (Japan) and Pacific Northwest National Laboratory (USA). Members will use existing funding, apply for grants together, and perform projects with industry and receive industry support. All these options, as well as more ambitious plans, are in place.

ACTIVITIES

The activities of the Consortium will include the following:

• Define a set of appropriate experimental model systems to be used by the Consortium to study various aspects of RTK signaling, including various disease contexts, dynamic properties, spatial regulation, and effect of drugs and therapeutic modalities

• Collect, integrate, and improve computational models and analytical methods necessary to study RTK signaling networks

• Create and maintain a distributed database that allows data- and model-sharing among Consortium members

• Produce and collect the large amounts of high-quality data necessary for modeling, and standardize technology and methods needed for data production

• Host a web site for disseminating Consortium results to the general scientific community and providing information on Consortium activities

• Hold workshops in which computational and experimental scientists work together to determine activities necessary to further improve RTK network models

• Hold workshops where scientists and clinicians design research programs that could improve therapies

• Provide cross-disciplinary training courses to improve communi cation between experimental and mathematical participants, and to facilitate their productive interactions

• Communicate with relevant research and advocacy groups such as pharmaceutical industry clinicians and patients to increase their involvement with the Consortium's research program

• Provide an integrated computational platform to the Consortium members for representation, simulation, and data handling

• Define the most critical technologies that need to be developed and data that need to be collected

• Promote and coordinate grant applications of members to enhance synergy and complementation, reduce duplication of effort, and increase accessibility to expensive core facilities

• Educate a new generation of researchers in the systems biology of RTK signaling and gene networks.

OUTREACH AND PUBLIC RELATIONS

The Consortium will have regular communication with the general public, in particular with relevant patient groups to educate and to increase their involvement with the Consortium's research program.

MEMBERSHIP

The Consortium will welcome the participation of outstanding research groups that will significantly contribute to its mission. Decisions on admission to the Consortium will be made by the executive committee with input from the international advisory committee.