Bethesda (Pook's Hill) Marriott Hotel, Bethesda, MD
March 3-4, 2003

NIDA Organizer(s): The Workshop was organized by Karen Skinner, Ph.D. under the auspices of the NIDA Emerging Technologies   Workgroup. Christine Colvis, Ph.D. served as co-chair at the meeting.

Purpose & Intent

• To bring together scientists from a variety of disciplines (including neuroscience, computation, informatics, and systems biology) to discuss how the study of proteomes and proteins (alone and combined with other studies, such as gene expression, lipidomics, etc.) can aid in understanding the classification and function of neuronal cells based on the properties of their intracellular networks.
• To discuss and explore the relevance of systems biology at the cellular level for understanding the actions of drugs, and endogenous molecules stimulated by exogenous factors (such as behavior, stress, diet, time, the environment, etc) on different neuronal cell types.
• To identify possible model cells, tissues, sub-proteomes,   and metabolic, genetic, or signaling molecular networks which may form the basis of a research strategy for undertaking studies of neuronal systems at the cellular level, and which would benefit from studies of their proteomes.
• To discuss strategies and tools for acquiring, managing and integrating information from proteomic and other systems research relevant to understanding neuronal cellular networks, and the research paradigms necessary to implement these strategies.
• To identify research goals which may be accomplished over the next 10-15 years in terms of understanding protein and other networks comprising neuronal cells, and their potential relevance to biomedical translational applications.
• To identify research gaps and opportunities which, if addressed, may enhance and accelerate understanding of the properties and actions of networks constituting neuronal cell types.

To explore how applications of systems biology in other areas may relate to neuroscience and drug abuse research, and to foster new research collaborations.

Meeting Outcome

The following points were emphasized during the presentations and collective discussions during the workshop:

• Current efforts should work towards systems biology and think beyond current uses of data.   Good systems analyses may be five years in the future because of critical quantitative data needs, but standardization in terms of data gathering and storage is needed now to enable future analyses.
• Improved   technologies   which encourage quantitative approaches and provide better quantitative data are needed
• Standards are important in defining biological time constants and frequency of measures
• Rather than limiting systems studies to standards of particular cell or tissue types, flexibility should be exercised in terms of biological systems studied. . Simpler model systems may be particularly useful when developing   technologies.
• Many specific functional biological questions remain which are best addressed through the efforts of individual laboratories, rather than high-throughput means. .
• Modelers and technologists should work together to develop quantitative technologies and models.
• Biological "modules," rather than whole systems, should be studied initially. The study of cellular subcompartments and their function -- for example neuronal terminals, spines or growth cones, and subcellular proteomes, such as the mitochondria --appear particularly manageable and attractive. Modules could also include particular functions such as signal transduction or endocytosis.
• A need exists for cell maps which incorporate modular and subcompartment data
• Biological studies should be at various levels of organization to fill the need for layered descriptions of networks
• An enormous need exists for desktop and PC tools which capture experimental conditions. Most existing laboratory management systems capture clinical type data, not data for basic research.
• A vision is needed of how biologists will interact with the grid; to provide interfaces for them, and provide a means for informing basic scientists of tools which are available
• A need exists for molecular tools which enable correlations with phenotypes

Expected Follow-up

The workshop is expected to continue to provide important insights into the planning and programmatic directions for NIDA's future initiatives and efforts in the application of systems approaches to the study of substance abuse, and in proteomics, and in NIDA's coordination with other NIH programs and activities in these areas. (Note: On April 28, 2003, NIDA issued RFA DA-04-004, "NIDA NEUROPROTEOMICS RESEARCH CENTERS")

Brief Description of Resulting Publications:

A formal meeting report was not published; however, a summary of the workshop's discussions was provided to the NIH RoadMap working group on Networks and Pathways. The workshop also was included as among those whose discussions and outcomes were considered by the Interagency Modeling and Analysis Group (IMAG) in shaping a new initiative just released: NSF Program Solicitation 04-067, " Interagency Opportunities in Multi-Scale Modeling in Biomedical, Biological, and Behavioral Systems." The workshop also served as one of the sources of background information which aided the planning of the first NIH symposium on "Digital Biology," including the associated NSF satellite event: "Information Processing in the Biological Organism (A Systems Biology Approach)"

Participants