Workshop on Protein - Protein Interaction Maps for the Mammalian Nervous System

Workshop on Protein-Protein Interaction Maps for the Mammalian Nervous System
November 17-18, 2004
Bethesda Marriott Hotel, Bethesda, Maryland

Organizing Committee: NINDS: Raul A. Saavedra, Ph.D.; Robert Baughman, Ph.D.; Danilo Tagle, Ph.D.; Randall Stewart; NIMH: Laurie Nadler, Ph.D.; Michael Huerta, Ph.D.; NIA: Bradley Wise, Ph.D.; NIAAA: Antonio Noronha, Ph.D.; NIDCD: Christopher Platt, Ph.D.; NIDA: Christine Colvis, Ph.D.; NCRR: Douglas Sheeley, Ph.D.

Sponsoring Institutes: NINDS; NIMH; NIA; NIAAA and NIDCD.

Summary: A group of twenty-five national and international investigators participated in this one-and-a-half day workshop (November 17-18, 2004). The group was comprised of scientists with diverse research backgrounds, including genomics/proteomics, investigators already constructing protein-protein interaction maps for model organisms (yeast, C. elegans and Drosophila), researchers developing relevant novel technologies, experts in bioinformatics, and basic and clinical neuroscientists. The workshop addressed the following issues: 1) Evaluate the need of protein-protein interaction map(s) for the mammalian nervous system to facilitate and enhance the research of the basic and clinical neuroscience communities, 2) evaluate the feasibility of constructing these maps for mammalian organisms and delineate strategies to accomplish these objectives, 3) identify available resources and a cadre of scientists to generate these maps and 4) identify the need for novel technologies and infrastructure required to achieve these objectives. The workshop consisted of three introductory presentations designed to provide all participants a common background and outline the major issues, four topic-specific discussion sections and a final general discussion session. The workshop participants reached conclusions about general aspects of protein interaction maps for the mammalian nervous system, the development of methodologies and informatics tools, as well as suggested ways on how to proceed with the project.

Workshop Purpose: The purpose of this workshop was to evaluate the usefulness and feasibility of mounting a coordinated effort to generate a protein-protein interaction map(s) for mammalian nervous system proteins. Such an effort would be a focused component of a broader neuroproteomics program. The workshop included the participation of experts in protein-protein maps for model organisms (yeast, C. elegans and Drosophila), neuroproteomics and bioinformatics, as well as independent commentators (i.e., basic and clinical neuroscientists who are knowledgeable in the field of general proteomics but do not conduct direct research on the subject). The workshop addressed specific needs and priorities of the neuroscience community that can be met by the generation of global maps of functional protein-protein interactions for the mammalian nervous system, assessed the feasibility of constructing these maps (including an assessment of scientific, technologic and infrastructure assets) and delineated potential strategies to accomplish this objective. Workshop participants: 1) considered protein classes that present specific challenges, such as membrane proteins, transiently-interacting proteins and proteins that exhibit mobility within and between cellular compartments, 2) examined the role of post-translational modifications in protein-protein interactions, 3) addressed general issues related to the interactions of proteins with other cellular components, 4) identified technologies that can meet these challenges, and 5) examined technologies that can efficiently validate the functional relevance of protein-protein interactions detected by the high throughput analytical methods. The participants reached conclusions on the significance of protein interaction maps in neuroscience, ways to transform these maps into effective tools for basic and clinical neuroscientists, as well as discussed the complexities associated with the archiving, management and maintenance of the massive amount of associated data.

Significance: The completion of the human genome (International Human Genome Consortium, Nature 409, 860-921, 2001; Venter et al., Science 291 1304-1351, 2001), the recent advances in the analysis of complex systems (Hood et al., Science 640-643, 2004), and the availability of improved biochemical, genetic and informatics tools, have facilitated major advances that make possible the integration of an increasing amount of biomedical information in the form of maps representing functional interactions of thousands of proteins. The maps provide valuable functional information on protein-coding genes and their products, can be readily integrated with gene expression data, protein structure/function and human disease-relevant information, and can represent an entire organism, an organ, a cell type, or even a cellular organelle. Furthermore, these maps are powerful tools in both basic and clinical research, since the identification of protein partners facilitates, in turn, the annotation of protein-coding genes/gene products, the discovery of new and the expansion of previously known cellular (metabolic and signaling) pathways, the elucidation of interactions among pathways and their integration into networks, the discovery of genes involved in human diseases and the identification of potentially beneficial/deleterious interactions for clinical applications. Therefore, these maps can serve as a basis for facilitating productive exchanges between basic and clinical neuroscientists.

Rationale and Goals: A previous "Workshop on Proteomics in the Neurosciences" (December 9-10, 2002) organized by Dr. Danilo Tagle and Dr. Randall Stewart identified the increasing needs of the neuroscience community to have ready access to integrated, experimentally-validated, large-scale functional information on proteins of the nervous system. These needs included the systematic annotation of interacting partners (other proteins, lipids, carbohydrates and metabolites) in order to better understand protein functions in a cellular, tissue and organ context. One way to address these needs is to generate maps that represent functional interactions of thousands of proteins. These protein-protein interaction maps can serve as a suitable base to anchor structural, genomics/gene expression, small interfering and micro RNAs (siRNA/miRNA), protein function and post-translational modifications, metabolic/signaling pathways and genetics/clinically-relevant information, as has been already demonstrated by the maps generated for model organisms, such as yeast (Uetz et al. Nature 403, 623-627, 2000; Gavin et al. Nature 415, 141-147, 2002; Han et al. Nature 430, 88-93, 2004), C. elegans (Li et al. Science 540-543, 2004) and Drosophila (Giot et al., Science 302, 1727-1736, 2003). The maps can represent an entire organism (such as the examples cited above), a particular cell type (such as neurons or glia), a tissue or an organ (such as the mammalian brain; see Choudhary and Grant, Nature Neuroscience 7, 440-445, 2004). Furthermore, these maps can be powerful research tools at both the basic and clinical levels, since the identification of protein partners facilitates the characterization of cellular/metabolic pathways (Bouwmeester et al., Nature Cell Biology 6, 97-105, 2004), the elucidation of interactions among pathways, the discovery of genes involved in human diseases and the identification of potentially beneficial/deleterious interactions for clinical applications. The novel information contained in these maps could have a significant impact on neuroscience research and thereby facilitate the rapid flow of mechanistic knowledge between basic and clinical neuroscientists and its subsequent translation and application to alleviate the burden of disease.

The overall goals of this workshop were to: 1) critically assess whether the construction of protein-protein interaction map(s) for the mammalian nervous system meets specific needs of the basic and clinical neuroscience communities, and can promote significant advancement of the neurosciences, 2) determine the feasibility of constructing these maps for mammalian organisms, 3) delineate strategies to accomplish these objectives, 4) identify/attract a cadre of scientist capable of generating these maps and 5) identify the needs for developing new technologies and infrastructure required to achieve the objectives. Specific goals for workshop participants were to give special consideration to proteins that present unique challenges to experimental manipulation, such as membrane, transiently-interacting and highly mobile proteins, and to the role of post-translational modifications in the regulation/modulation of protein-protein interactions, as well as identify existing and novel technologies designed to meet these challenges. The participants also addressed issues related to the ways and means to facilitate the archiving, maintenance, rapid and easy access, and utilization of the large amount of information contained in these maps by the basic and clinical neuroscience communities.

Agenda: The workshop format consisted of three general presentations designed to introduce the overall subject of the workshop, followed by four discussion sessions planned to address specific issues and by a final session intended for a general discussion and summary of conclusions. Each section began with a brief presentation by a discussion leader(s) followed by an in-depth discussion of the specific topics by assigned discussants and other workshop participants. For each session, the discussion centered on a list of questions provided to participants prior to the workshop that served as an overall guide, but discussants were also encouraged to pose their own questions and approach the issues from distinct perspectives. Throughout the discussion, independent commentators provided their "outside" views, and thus actively contributed and enriched the discussion. The topics of the different sessions were intimately related to one another, which contributed to fruitful interactions among all of the participants. This format served very well the need to focus the discussion of a very diverse group of researchers representing many different scientific disciplines.

General Introductory Presentations:

1. What are protein interaction maps? Specific examples of maps currently available for model organisms. Presenter: Dr. Richard Morrison.
2. The challenges of constructing protein interaction maps of the nervous system. Presenter: Dr. Seth Grant.
3. Current developments in bioinformatics of proteomics. Presenter: Dr. Rolf Apweiler.

Session 1: Protein-protein interaction maps for the mammalian nervous system in basic and clinical neurosciences. The assigned discussants for this session were Drs. Allan Butterfield, Christine Gall (Commentator), Gwenn Garden, Howard Gendelman, Seth Grant, Richard Morrison and Gabriele Ronnett. The discussion co-leaders were Drs. Seth Grant and Richard Morrison. The participants addressed the following questions:

1. What specific research needs in the basic neuroscience community can be fulfilled by protein-protein interaction maps of the mammalian nervous system?
2. What are the specific needs in the clinical neuroscience community for these maps?
3. Are there novel ways to organize these maps that could expedite the flow of information and ideas between the two communities?
4. Can we design new ways to use this information and thus accelerate the progress of translational neuroscience research?

Session 2: Feasibility of generating protein-protein interaction maps for the mammalian nervous system. The assigned discussants for this session were Drs. Joel Bader, Marc Flajolet, David Hill, John Kusiak (Commentator) and Edward Marcotte. The discussion leaders were Drs. David Hill and Edward Marcotte. The participants addressed the following questions:

1. Should a single protein-protein interaction map for the entire nervous system be generated, or should separate maps be made of specific regions of the nervous system (such as forebrain, cerebellum, spinal cord and peripheral system)?
2. Should a single map of a "nervous system cell" be generated, or should distinct maps for specific cell types (such as neurons and glia) be made?
3. Should we consider a targeted protein-protein interaction map(s) that would facilitate translational neuroscience research?
4. Should the map be anatomically-driven or biochemical/signaling pathway-driven?
5. How can we better accommodate information relevant to different stages of development in these protein interaction maps?
6. Should the focus be on the human nervous system or on a model organism such as the mouse? Or both?
7. What methods and analytical tools are already available for the construction of protein interaction maps?
8. Are these methods and analytical tools adequate for studying the nervous system? For example, specific questions might include:
9. What are the most likely obstacles? How can these obstacles be overcome? What infrastructure is required to facilitate the construction of the map(s)? What resources are already available? What are the financial costs of the major aspects of such a project?

Session 3: Application/development of novel technologies to study protein-protein interactions in the nervous system. The assigned discussants for this session were Drs. Susan Amara (Commentator), Michael Browning, Erica Golemis, Tom Kerppola, Andrew Link, Alexander Sorkin and David Teplow. The discussion leader was Dr. David Teplow. The participants addressed the following questions:

1. What new methods and analytical tools need to be developed, if any, to approach membrane, transiently-interacting and mobile proteins?
2. What tools should be developed to approach the effects of post-translational modifications on protein-protein interactions?
3. Are there other specialized proteins of the nervous system that would require ad-hoc analytical tools?
4. Can we expedite the functional validation of protein-protein interactions detected by high throughput systems, such as the yeast two-hybrid or tandem affinity purification? For example, can be developed ancillary high throughput systems designed to validate the functional significance of protein-protein interactions?

Session 4: Informatics, management and maintenance of the data. The assigned discussants for this session were Drs. Rolf Apweiler, David Fenyo, Maryann Martone (Commentator), Lukasz Salwinski and David Wheeler. The discussion leaders were Drs. Rolf Apweiler and David Wheeler. The participants addressed the following questions:

1. How to best archive and manage the large amount of data generated?
2. Where to store the data?
3. How to organize these maps in a way that optimize, clarify and facilitate their use?
4. How to archive and manage data on nervous system proteins derived from studies using models other than the nervous system?
5. How to link other biomedical relevant information, including protein structure, RNA and gene expression data, gene annotation, siRNA and human disease information to these maps?

Session 5: General discussion and summary of conclusions. The overall discussion leaders were Drs. Seth Grant and Richard Morrison. The purpose of this session was to revisit major issues and summarize the conclusions of the workshop:

1. Are nervous system protein interaction maps needed to achieve significant progress in basic and clinical neurosciences?
2. Is the construction of brain protein interaction maps feasible and in what format?
3. Are the required expertise, technologies and infrastructure already available or should we also develop novel methods and tools to approach the interactions of specialized nervous system proteins?
4. What is the best way to archive, manage and maintain the large amounts of data that will be produced?
5. What are the overall cost-benefit considerations in carrying out such a project?

Workshop Conclusions: The following points summarize the major conclusions achieved by the workshop participants. These conclusions are presented in four categories: General aspects, Methodologies and experimental issues, Bioinformatics tools and How to proceed.

Conclusions on General Aspects of Protein Interaction Maps for the Mammalian Nervous System:

1. There is a strong need for neural protein-protein databases and for the adequate integration of these data with other biological information (i.e., gene expression, anatomy) in a manner that facilitates their utilization.
2. Biology should be the major driving force for selecting proteins for investigation, as opposed to random selection.
3. Both whole organism and neural-specific interaction maps are important, since many genes/proteins are expressed widely, but their mutated variants selectively affect the nervous system. For example, the retinoblastoma (Rb) gene/protein is involved in cell cycle regulation and is expressed in all cell types, but mutations of this gene lead selectively to tumors in the retina. Both static and dynamic (following a perturbation of the system) maps are important.
4. All databases must be readily up-datable and amenable to improvement. Some participants proposed the idea of developing, in parallel, a repository of "no-interactions", which would include proteins that are known not to interact with one another under well defined conditions; even though experimental "false negatives" are common and negative interactions are difficult to interpret.
5. Sets of proteins, such as complexes involved in human disease (Alzheimer's, Huntington, Parkinson, etc.), synaptosome/scaffolding proteins and signal transduction pathways are good initial targets. Some participants suggested to begin with a set of a few hundred "favorite" genes/proteins and then to scale up the process. A possible approach is to survey the neuroscience community to select the initial set of genes/proteins.
6. Interactions of membrane proteins in particular should be targeted because they are critical to neural function and are underrepresented in the existing techniques.
7. Interactions of mobile (within and between cellular compartments) proteins, transient protein interactions and post-translational modifications are also essential and underrepresented.
8. The information contained in available orthologous protein interaction maps for model organisms such as yeast, C. elegans and Drosophila can be used to refine mammalian nervous system maps. The available maps, however, exhibit limited overlap.

Conclusions on Methodological and Experimental Issues:

1. There is a need to enhance technology development to study neural membrane proteins and other underrepresented neural proteins. Any approach should be flexible and open to the incorporation of novel technologies.
2. The coordinate utilization of complementary methods (including mass spectrometry, yeast-two hybrids, affinity capture, fluorescence resonance energy transfer and sub-cellular/anatomical localization) is important to ensure maximum completeness of the maps.
3. Both single gene/protein and genome-wide tools need to be developed. Well characterized reagents, including ORF libraries, tagged proteins and antibodies should be shared to facilitate the completion of the maps.
4. Cell lines, such as stem or pluripotent cells are appropriate sources of biological material. Human nervous tissues, which are obtained from surgery or autopsy, are problematic, owing to practical difficulties associated with obtaining the tissue, variable post-surgical and post-mortem intervals and tissue heterogeneity, which collectively influence the reproducibility of results. Animal models, such as mice, are advantageous due to their well studied anatomy, physiology, behavior and molecular genetics, as well as their ready availability.

Informatics Tools:

1. The existing protein interaction databases are incomplete and not sufficiently "user-friendly". Research groups store proteomics data but do not use a standard nomenclature for genes/proteins, which makes data mining inefficient. There is a need to develop a "Thesaurus" approach and efforts are already underway to better coordinate existing maps. There is also a need to validate existing data and to incorporate all the information available including low confidence data with proper caveats and alerts.
2. A major problem in handling proteomics information is not the amount of data but its complexity (organization).
3. There is a need to generate/expand specific proteomics databases for the neuroscience community.
4. The protein interaction data must be linked to complementary biological information, such as protein/gene structure, protein/gene function, expression, regulation, siRNA, transgenic and null-mutant model information, cell type/anatomic localization, behavior, etc. It is essential to "clean-up" the data from the initial stages.
5. Neural protein interaction maps can be linked to existing protein/gene databases, such as BIND (Biomolecular Interaction Network Database; http://bind.ca), FlyBase (http://flybase.bio.indiana.edu), WormBase (http://www.wormbase.org), GRID (General Repository of Interaction Datasets; http://biodata.mshri.on.ca/grid/servlet/Index), the InterPro Consortium (http://www.ebi.ac.uk/interpro), etc.
6. There is a need to generate readily interpretable displays for summarizing protein interaction data.
7. Establish a group of researchers that can start mining available protein interaction data in an organized fashion. This is a cost-effective way to proceed with this project and some efforts are already underway.
8. Develop automated tools for uniformly entering data.
9. Work in coordination with journals to establish standards requiring that submitted data are stored and made accessible in public databases and not "locked-up" in supplementary data depositories.
10. Education and training in both the generation and use of protein interaction maps and in bioinformatics are critical.
11. Encourage the development of international collaborations. It is important to integrate new efforts with those already under way.

How to Proceed:

Workshop participants defined two major phases that can proceed in parallel:

Phase I:

Data mining, informatics, training and data sharing.
A. Establish a group of researchers to identify and collate existing data into a neural protein interaction database and coordinate this effort with existing orthologous maps.
B. Promote training in the generation and use of interaction maps and in protein bioinformatics.
C. Coordinate with journals to ensure that submitted data are properly stored and made fully accessible.
D. Encourage collaborative international efforts in data analysis and sharing.

Phase II:

Experimental analysis.
A. Let biology direct the mapping studies. Develop a consensus on several hundred neural proteins as the initial focus for mapping.
B. Develop technology to improve the mapping of interactions for membrane and other underrepresented neural proteins.
C. Generate protein-interaction reagents and tools, including cDNA libraries, tagged proteins (GST-TAP, GTP-TAP), siRNAs, etc., and make them freely available to the research community.

Workshop Participants:

Susan G. Amara, Ph.D.
Thomas Detre Professor and Chair
Department of Neurobiology
University of Pittsburgh School of Medicine
Co-Director
Center for Neuroscience
3500 Terrace Street
BSTWR, E1440
Pittsburgh, PA 15261
Phone: 412-383-8910
Fax: 412-648-1441
E-mail: amaras@pitt.edu

Rolf Apweiler, Ph.D.
Head of Sequence Database Group
European Bioinformatics Institute
Wellcome Trust Genome Campus
Hinxton, Cambridge CB10 1SD
United Kingdom
Phone: 44 1223 49 4435
Fax: 44 1223 49 4486
E-mail: apweiler@ebi.ac.uk

Joel S. Bader, Ph.D.
Assistant Professor
Department of Biomedical Engineering
Johns Hopkins University
Clark Hall, Room 201C
3400 North Charles Street
Baltimore, MD 21218
Phone: 410-516-7417
Fax: 410-516-5294
E-mail: joel.bader@jhu.edu

Robert W. Baughman, Ph.D.
Associate Director for Technology Development
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Neuroscience Center Building, Room 2137
6001 Executive Boulevard
Bethesda, MD 20892
Phone: 301-496-1779
Fax: 301-402-1501
E-mail: rb175y@nih.gov

Michael Browning, Ph.D.
Professor
Program in Neuroscience
Department of Pharmacology
University of Colorado Health Sciences Center
P.O. Box 6511, Mail Stop 8303
Aurora, CO 80045-0508
Phone: 303-724-3638
Fax: 303-724-3640
E-mail: michael.browning@uchsc.edu

D. Allan Butterfield, Ph.D.
Alumni Professor of Biological Chemistry
Director
Center of Membrane Sciences
Department of Chemistry
University of Kentucky
121 Chem-Phys Building
Lexington, KY 40506-0055
Phone: 859-257-3184
Fax: 859-257-5876
E-mail: dabcns@uky.edu

David Fenyo, Ph.D.
Staff Scientist
GE Healthcare
800 Centennial Avenue
Piscataway, NJ 08855
Phone: 917-754-6066
Fax: 928-244-5862
E-mail: david.fenyo@amersham.com

Marc Flajolet, Ph.D.
Research Associate
Department of Molecular and Cellular
Neuroscience
Rockefeller University
1230 York Avenue
New York, NY 10021
Phone: 212-327-8788
Fax: 212-327-7888
E-mail: flajolm@rockefeller.edu

Christine M. Gall, Ph.D.
Professor
Department of Anatomy and Neurobiology
837 Health Science Drive
Gillespie Neuroscience Research Facility
University of California, Irvine
Irvine, CA 92697-4292
Phone: 949-824-8652
Fax: 949-824-1255
E-mail: cmgall@uci.edu

Gwenn A. Garden, M.D., Ph.D.
Assistant Professor
Department of Neurology
University of Washington
Box 356465
Seattle, WA 98195
Phone: 206-221-5118
Fax: 206-685-8100
E-mail: gagarden@u.washington.edu

Howard E. Gendelman, M.D.
Professor and Chair
Department of Pharmacology
Director
Center for Neurovirology and
Neurodegenerative Disorders
University of Nebraska Medical Center
985880 Nebraska Medical Center
Omaha, NE 68198-5880
Phone: 402-559-4035
Fax: 402-559-3744
E-mail: hegendel@unmc.edu

Erica A. Golemis, Ph.D.
Member
Division of Basic Science
Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia, PA 19111
Phone: 215-728-2860
Fax: 215-728-3616
E-mail: ea_golemis@fccc.edu

Seth G.N. Grant, BSc (Medicine), MB, BS
Professor
Team 32 - Genes to Cognition
Wellcome Trust Sanger Institute
Hinxton, Cambridge
Cambridgeshire CB10 1SA
United Kingdom
Phone: 44 1223 494 908
Fax: 44 1223 494 919
E-mail: sg3@sanger.ac.uk

Deborah B. Henken, Ph.D.
Developmental Biology, Genetics, and Teratology Branch
National Institute of Child Health and Human Development
National Institutes of Health
Executive Building, Room 4B01
9000 Rockville Pike, MSC 7510
Bethesda, MD 20892-7510
Phone: 301-496-5541
Fax: 301-480-0303
E-mail: dh50g@nih.gov

David E. Hill, Ph.D.
Senior Research Scientist
Associate Director
Center for Cancer Systems Biology
Department of Cancer Biology
Dana-Farber Cancer Institute
Harvard Medical School, SM858
44 Binney Street
Boston, MA 02115
Phone: 617-632-3802
Fax: 617-632-5739
E-mail: david_hill@dfci.harvard.edu

Michael F. Huerta, Ph.D.
Associate Director
National Institute of Mental Health
National Institutes of Health
Neuroscience Center Building, Room 7202
6001 Executive Boulevard, MSC 9645
Bethesda, MD 20892-9645
Phone: 301-443-3563
Fax: 301-443-1731
E-mail: mhuert1@mail.nih.gov

Tom K. Kerppola, Ph.D.
Associate Professor
Department of Biological Chemistry
Howard Hughes Medical Institute
University of Michigan
MSRB II, Room 4570
1150 West Medical Center Drive
Ann Arbor, MI 48109-0650
Phone: 734-615-1703
Fax: 734-615-3397
E-mail: kerppola@umich.edu

John W. Kusiak, Ph.D.
Program Director
Molecular and Cellular Neurobiology Program
Division of Basic and Translational Sciences
National Institute of Dental and Craniofacial Research
National Institutes of Health
Building 45, Room 4AN 18A
45 Center Drive
Bethesda, MD 20892
Phone: 301-594-7984
Fax: 301-480-8319
E-mail: john.kusiak@nih.gov

Story Landis, Ph.D.
Director
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Building 31, Room 8A52, MSC-2540
31 Center Drive
Bethesda, MD 20892
Phone: 301-496-9746
Fax: 301-496-0296
E-mail: landiss@ninds.nih.gov

Andrew J. Link, Ph.D.
Assistant Professor
Department of Microbiology and Immunology
Vanderbilt University School of Medicine
465 21st Avenue, South
Nashville, TN 37232
Phone: 615-343-6823
Fax: 615-343-7392
E-mail: andrew.link@vanderbilt.edu

Edward M. Marcotte, Ph.D.
Assistant Professor
Director
Center for Systems and Synthetic Biology
Department of Chemistry and Biochemistry
University of Texas
MBB 3.232
2500 Speedway
Austin, TX 78712
Phone: 512-471-5435
Fax: 512-232-3432
E-mail: marcotte@icmb.utexas.edu

Maryann E. Martone, Ph.D.
Associate Adjunct Professor
Department of Neuroscience
University of California, San Diego
MC 0715
9500 Gilman Drive
San Diego, CA 92093-0715
Phone: 858-822-0745
Fax: 858-822-0828
E-mail: maryann@ncmir.ucsd.edu

Richard S. Morrison, Ph.D.
Professor
Department of Neurological Surgery
University of Washington
Box 356470
1959 N.E. Pacific Street
Seattle, WA 98195
Phone: 206-543-9654
Fax: 206-543-8315
E-mail: yael@u.washington.edu

Laurie S. Nadler, Ph.D.
Chief, Basic Neuroscience Centers Program
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
National Institutes of Health
Neuroscience Center Building, Room 7200
6001 Executive Boulevard, MSC 9645
Bethesda, MD 20892-9645
Phone: 301-443-3563
Fax: 301-443-1731
E-mail: lnadler@mail.nih.gov

Antonio Noronha, Ph.D.
Director
Division of Neuroscience and Behavior
National Institute of Alcohol Abuse and Alcoholism
National Institutes of Health
5635 Fishers Lane, Suite 2061,
Bethesda, MD 20892-9304
Phone: 301-443-7722
Fax: 301-443-1650
E-mail: anoronha@mail.nih.gov

Christopher Platt, Ph.D.
Program Director
Hearing and Balance/Vestibular Sciences
National Institute on Deafness and Other Communication Disorders
National Institutes of Health
6120 Executive Boulevard, Suite 400
Bethesda, MD 20892
Phone: 301-496-1804
Fax: 301-402-6251
E-mail: plattc@nidcd.nih.gov

Gabriele V. Ronnett, M.D., Ph.D.
Professor
Department of Neuroscience
Johns Hopkins University School of Medicine
PCTB, Room 1006
725 North Wolfe Street
Baltimore, MD 21205
Phone: 410-614-6482
Fax: 410-614-8033
E-mail: gronnett@jhmi.edu

Raul A. Saavedra, Ph.D.
Scientific Review Branch
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Neuroscience Center Building, Suite 3208
6001 Executive Boulevard
Bethesda, MD 20892-9529
Phone: 301-496-7355
Fax: 301-402-0182
E-mail: saavedrr@ninds.nih.gov

Lukasz Salwinski, Ph.D.
Assistant Researcher
DOE Institute for Genomics and Proteomics
University of California, Los Angeles
Boyer Hall, Room 205
611 Young Drive
Los Angeles, CA 90095
Phone: 310-825-1402
Fax: 310-206-3914
E-mail: lukasz@mbi.ucla.edu

Douglas M. Sheeley, Sc.D.
Division of Biomedical Technology
National Center for Research Resources
National Institutes of Health
6701 Democracy Boulevard, MSC 4874
Bethesda, MD 20892-4874
Phone: 301-594-9762
Fax: 301-480-3659
E-mail: sheeleyd@mail.nih.gov

Roger G. Sorensen, Ph.D., M.P.A.
Division of Neuroscience and Behavior
National Institute of Alcohol Abuse and Alcoholism
National Institutes of Health
5635 Fishers Lane, Room 2058, MSC 9304
Bethesda, MD 20892-9304
Phone: 301-443-2678
Fax: 301-443-1650
E-mail: rsorense@mail.nih.gov

Alexander Sorkin, Ph.D.
Associate Professor
Department of Pharmacology
University of Colorado Health Sciences Center
Fitzsimmons Campus
P.O. Box 6511, Mail Stop 8303
Aurora, CO 80045-0508
Phone: 303-724-3649
Fax: 303-724-3663
E-mail: alexander.sorkin@uchsc.edu

David Teplow, Ph.D.
Associate Professor
Department of Neurology
Brigham and Women's Hospital
HIM-756
77 Avenue Louis Pasteur
Boston, MA 02115
Phone: 617-525-5270
Fax: 617-525-5252
E-mail: teplow@cnd.bwh.harvard.edu

Brad Wise, Ph.D.
Program Director, Fundamental Neuroscience
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
National Institutes of Health
7201 Wisconsin Avenue, Suite 350
Bethesda, MD 20892-9205
Phone: 301-496-9350
Fax: 301-496-1494
E-mail: wiseb@nia.nih.gov