ILAR Journal Online, Volume 34(3) 1992: ILAR's Fortieth Anniversary

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ILAR Journal V34(3) 1992 [FORMERLY ILAR NEWS]
ILAR's Fortieth Anniversary

The Biological Models and Materials Research (BMMR) Program, National Center for Research Resources, National Institutes of Health
Louise E. Ramm and Elaine Young

Louise E. Ramm, Ph.D. is director of and Elaine Young, Ph.D. is Health Sciences Administrator for the Biological Models and Materials Research Program, National Center for Research Resources, National Institutes of Health, Bethesda, Maryland.

Background and Introduction

The goal of the Biological Models and Materials Research (BMMR) Program of the National Center for Research Resources (NCRR), National Institutes of Health (NIH) is to increase the variety and utility of nonmammalian models for biomedical research. The BMMR Program is accomplishing this mission in two ways: by establishing resource facilities that supply biomaterials and non-mammalian organisms to the research community and by supporting the development of model systems such as poikilothermic vertebrates, invertebrates, cell and tissue culture systems, and nonbiological (mathematical and computer) models.

The BMMR program originated in 1985 as an integral part of the Comparative Medicine Program (formerly called Animal Resources Program), NCRR and attained full program status in 1989. Initial projects focused on center grants and contracts to supply investigators with a variety of lower organisms and biomaterials. Since then, the program has expanded to support the development of new models and to make available useful model systems and critical biomaterials to the research community. These approaches include, but are not limited to, investigator-initiated grants, resource-related grants, resource grants, First Independent Research Support and Transition (FIRST) Awards, Academic Research Enhancement Award (AREA), and Small Business Innovation Research (SBIR) grants.

Investigator-Initiated Research Grant (R01)

BMMR provides grants to support research and development of model systems such as all poikilothermic organisms, including lower vertebrates, invertebrates, microorganisms, and nonbiological systems. Cell and tissue culture models derived from nonmammalian sources or established mammalian cell lines are also considered appropriate. In general, research on broad intertaxonomic projects or research on systems considered to be high connectivity models or to have the potential of becoming high connectivity models are of particular interest, including both organismic and theoretical models. High connectivity is defined in two ways: (1) those organisms or systems with many characterized properties or functions, such as Drosophila melanogaster, Caenorhabditis elegans, Aplysia Sp., Xenopus Sp., Arabidopsis Sp., Escherichia coli, and sea urchins; or (2) a function or property that is broadly retained across many taxa. Examples of the latter include cytoskeleton structure, cell adhesion, cytochrome c, hormones, and hormone receptors. Symbolic (theoretical) model systems, including computer, mathematical, and physical models, are also appropriate especially for projects that combine both symbolic and organismic model systems.

Of particular interest to the BMMR program in relationship to the development of nonbiological models is the investigation of the "matrix of biological knowledge" or "Biomatrix." Several years ago, the National Academy of Sciences recommended that the NIH investigate the Biomatrix as a potential tool for the biomedical community. The Biomatrix is defined as the organization, or complete data base, of all published biological and clinical data, and the theories and the analyses of these data. Thus, in addition to the actual data, the Biomatrix includes empirical generalizations, interconnections, laws, and models that are used to structure biological data. To pursue the Biomatrix concept, a mechanism to organize and intelligently access the large array of biological information must be developed. An assessment of the feasibility of this project was addressed in a 5-week workshop, conducted by the Santa Fe Institute and jointly funded by the BMMR program and other agencies. The workshop demonstrated that computer implementation of the Biomatrix concept is possible. The BMMR program is interested in proposals that address this research area. Recently, the BMMR program supported Biomatrix conferences and provided grants to collect and systematically integrate collections of biological data bases in order to provide researchers with greater access to particular information.

Resource Grant (P40)

The resource research centers supported by the BMMR program were established as centralized resource sites not only to facilitate dissemination of biomaterials to the research community, but also to develop well-characterized, documented, and high quality stocks and other biomaterials. Current BMMRP-supported resources are listed below. The program is interested in research resource projects involving various lower organisms, including marine or fresh water species, microorganisms, invertebrates, cell systems, or biomaterials (such as DNA probes and other genetic material). Resource grants provide funds for several purposes: to solve basic research problems, to maintain the resource, and to give lead time to the resource to establish a cost recovery system. Areas of research include, but are not limited to, fundamental studies associated with the culture, maintenance, and authentication that would make a particular organism or biomaterial generally useful and available to the biomedical research community.

Resource support is limited to organisms or biomaterials that are used for a variety of research projects and that span the interests of two or more institutes of the NIH. Relevance of the resource to the biomedical research community (whose members are primarily grantees and contractors of other NIH programs) must be demonstrated. Also, the user community that needs the resource and would make use of it must be identified. The program is also interested in research projects that contribute to the knowledge of nonmammalian model systems that are not currently considered well-used models, but that have the potential for becoming so.

Research Resources

Currently, the BMMR program supports 11 research resources or developing resources that supply a diverse assortment of biomaterials, including microorganisms, cell lines, human tissue and organs, genetic material, and a variety of invertebrates. Some of the resources are genetic mutant stock centers--mutant strains of many organisms are essential tools in biomedical research. Other facilities provide unique services, organisms, or biomaterials. All of these centers provide material to the scientific community for a nominal fee and/or shipping charges.

More detailed information on the resources can be obtained in the directory Resources for Biological Models and Materials Research, which is available from the Research Resources Information Center, 1601 Research Boulevard, Rockville, MD 20850. Tel: 1-301/251-4970; Fax: 1-301/480-2470. An overview of the various centers including their importance to the biomedical research endeavor follows.

The Caenorhabditis Genetics Center (CGC)

The Caenorhabditis Genetics Center (CGC) at the University of Minnesota, St. Paul, is a repository and distribution center for over 1,500 strains of the invertebrate nematode Caenorhabditis elegans and other Caenorhabditis species. The center, formerly located at the University of Missouri, includes in its collection at least one allele of each identified gene, all available chromosome rearrangements, and selected multiple-mutant stocks useful for genetic mapping. The center is also responsible for the annual revision of the C. elegans genetic map, the coordination of the genetic nomenclature, and the maintenance of a complete bibliography of research in which C. elegans is used. The small size of C. elegans and its defined embryonic lineage make it a useful model for research in genetics, development, aging, muscle biology, and neurobiology.

Genetic Tool Kit for C. Elegans

The BMMR program supports a related activity to aid researchers working with the nematode C. elegans. A group at the University of British Columbia in Vancouver is generating a genetic tool kit, which is a comprehensive collection of chromosomal balancers for the C. elegans genome. The chromosome rearrangements will provide insights into the structural organization and function of chromosomes in pairing, meiotic segregation, and genetic recombination. The kit will be available in the form of genetic stocks, through the Caenorhabditis Genetics Center in St. Paul for use by investigators initiating or continuing research on this nematode. Sets of overlapping deletions will be provided for each chromosome as they become available. These will make up a high resolution mapping kit for aligning the genetic and physical maps and for mapping new mutations. The basic genetic tools will provide access to the biological function of every gene and, in conjunction with the C. elegans genome project, will provide a comprehensive foundation for understanding the biology of this animal model.

The American Type Culture Collection (ATCC)

The American Type Culture Collection (ATCC) in Rockville, Maryland, is a national repository dedicated to the collection, preservation, authentication, and distribution of an immense and diverse group of microbiological cultures and cell lines. The BMMR program supports the curatorial functions of this unique resource. The collections of the ATCC include over 15,000 strains of bacteria and 500 bacteriophages and plasmids; animal cell lines from 75 different species and hybridomas; the only general service collection of living fungi (including yeast) in the United States; over 2,000 animal viruses and 900 plant viruses; and more than 1,100 living strains of well-characterized protista (protozoa and algae). The ATCC responds to requests for over 100,000 cultures and cell lines each year and is the primary source of microbial standards for the scientific community. These biological materials are important to the full spectrum of biomedical and biological research from basic studies to clinical investigations.

The Repository of Mice and Human DNA Probes and Human Libraries

The Repository of Mice and Human DNA Probes and Human Libraries, located at the ATCC in Rockville, Maryland, was established as a centralized national resource to provide a means for researchers to exchange cloned human DNA, with the understanding that such a resource would facilitate studies of a wide range of human genetic diseases. The repository, cofunded by the National Institute of Child Health and Human Development and the NCRR, collects, maintains, and distributes well-characterized cloned human and mouse genes, DNA probes, and chromosome-specific libraries developed at the Los Alamos and Lawrence Livermore Laboratories. Over 20,000 clones have been distributed as well as 1300 chromosome-specific libraries. The quality of the probes deposited in the facility reflect the repository's objective to emphasize relevancy to human genetic disease.

The Yeast Genetic Stock Center

The Yeast Genetic Stock Center (YGSC) at the University of California, Berkeley collects, maintains, monitors, and distributes genetically well-characterized strains of the yeast, Saccharomyces cerevisiae. Each of over 1,000 strains available in the collection bears one to several mutant loci encompassing a wide range of functions of this eukaryotic organism. Also included in the collection are special categories of strains such as sets of "mapping strains," transformable strains, and other groups of mutants that facilitate studies in genetics, cell and molecular biology, and biotechnology. The stock center participates in the updating and publication of the genetic map of S. cerevisiae which currently includes more than 1,000 mapped genes of the estimated 6,000 genes present on its 16 chromosomes.

The National Cell Culture Center

The National Cell Culture Center in Minneapolis, Minnesota, provides large-scale mammalian cell culture services. The center, available to researchers throughout the United States, was established to alleviate the current shortage of facilities and expertise required to meet the cell culture needs of the biomedical research community. Specifically, the center provides investigators with the following customized services: large quantity production of mammalian cells in suspension or monolayer cultures in a range from 10 to 150 liters, large quantity production of monoclonal antibodies from 0.5 to 100 grams, and large quantity production of non-hybridoma cell secreted proteins. A large number of investigators working in areas such as cellular and molecular biology, immunology, cancer research, and gene expression use this resource.

Capture, Maintenance, and Culture of Loliginid Squids

A resource for the capture, maintenance, and culture of loliginid squids at the Marine Biomedical Institute in Galveston, Texas is under development. The basic objective of the resource is to supply investigators, particularly in neuroscience, with adult squids for giant axon preparations and other experimental procedures year-round. Currently, Lolliguncula brevis is locally available year-round for resident and visiting investigators, and wild-caught Loligo plei and Loligo pealei are seasonally available. Additional species of squids including Sepioteuthis lessoniana and Sepia officinalis are available in limited numbers through laboratory culture.

Information Clearinghouse for Laboratory Maintenance and Culture of Octopus for Biomedical Research

Located at Marine Biomedical Institute is an information clearinghouse for the laboratory maintenance and culture of octopus that provides information on the availability and suitability for culture of most octopus species in the coastal waters of North America. Detailed information is available for Octopus bimaculoides, O. briareus, O. digueti, O. joubini, O. maya, and O. vulgaris. The center can help investigators obtain limited numbers of these animals, including eggs and hatchlings, to initiate laboratory populations. Information can also be obtained on the potential uses of octopuses in biomedical research, especially in environmental toxicology, comparative psychology, genetics, and physiology.

Laboratory Culture of Hermissenda

Located at the Marine Biological Laboratory, Woods Hole, Massachusetts, is a center whose major objective is to develop methods that will reliably enable the nudibranch mollusc Hermissenda crassicornis to be reared and maintained in laboratory culture for the purpose of establishing it as a standardized nonmammalian marine laboratory animal for biomedical research. Currently, all life stages, including developing embryos, free swimming veliger larvae of all ages, newly metamorphosed juveniles, and mature adults, are available. The development of specific inbred strains that are well-adapted to laboratory culture and display specific character traits (e.g., learning abilities or ataxic behaviors) will enhance the use of this species as a model system in neurobiology.

The Center for Alternatives to Animal Testing (CAAT)

The Center for Alternatives to Animal Testing (CAAT) at the Johns Hopkins University School of Hygiene and Public Health in Baltimore, Maryland, is committed to developing and validating, to the extent consistent with maintaining public health and safety, in vitro alternatives to the use of whole animals for evaluating commercial and therapeutic products. CAAT also actively encourages the use of alternatives by disseminating scientifically correct information about them and by promoting recognition that in vitro methods act in concert with whole animal and clinical studies to advance science; develop new products and drugs; and treat, cure, and prevent disease.

The National Disease Research Interchange (NDRI)

The National Disease Research Interchange (NDRI) in Philadelphia, Pennsylvania serves as an interchange between human tissue sources (hospitals, organ recovery programs, eye banks) and investigators who require a reliable, steady supply of human tissues prepared precisely for research needs. As an individualized service to each participating investigator, the NDRI retrieves, processes, and delivers human tissue that is normally discarded. The NDRI has provided hundreds of researchers with human tissue and organs. Research in many disease areas such as diabetes, cancer, cystic fibrosis, Alzheimer's, glaucoma, Parkinson's, and multiple sclerosis has been advanced due to the availability of both normal and diseased human tissue.