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Nutrition Obesity Research Center at Harvard

Core Facilities

Cell Biology

David S. Newburg, PhD
Principal Investigator

The purpose of the Cell Biology Core has been and will continue to be to allow NORC investigators facile access to the specialized expertise and equipment in morphology, cell culture, immunology, and analytical glycobiology needed to efficiently advance their research interests in nutritional sciences and obesity.

The continuing rapid progress in nutritional sciences is being supported by understanding of basic processes of cell biology, particularly with regard to intracellular signaling among intestinal mucosa, intestinal microflora, cells of the immune system, adipose, endothelium, liver, and muscle. The complex interdependence of these systems is now becoming understood, due in large measure to the rapid advances in our research tools, especially new types of microscopy, sophisticated cell culture techniques, advances in immunology, and the ability to isolate and identify biologically active small molecules and complex glycans. These tools, historically used in isolated studies to address basic nutritional research questions, can be used in concert to expedite our ability to unravel inherently complex biological questions that help us address some of our most pressing nutritional issues, especially chronic conditions such as obesity, atherosclerosis, allergy, and many forms of cancer. Many projects can be advanced by the use of instruments and techniques whose expense and difficulty of first use represent a barrier to their incoporation into protocols. The Cell Biology Core is designed to overcome this barrier by providing full assistance to first-time users and training to NORC members who would like to use the technology on a more long-term basis. This arrangement saves costs, as expensive instruments are utilized more fully and can be used on a new project to explore novel or risky hypotheses without requiring a large investment. The Core has the twin goals of expediting the use of these technologies to resolve specific research questions, and transferring the technologies and expertise to the NORC investigator.

1. Morphology

The morphology service of the Cell Biology Core allows access to expertise in morphological approaches, training in advanced morphological techniques, and selected services relating to morphological evaluation critical to the work of investigators involved in this Center. One of the particular strengths of the morphology service of this Core is the comprehensive array of morphological and immunocytochemical techniques offered, from basic light microscopic localization studies on antigen localization in frozen and paraffin sections, to high resolution immunogold labeling on ultrathin frozen sections of cells and tissues. These techniques include immunofluorescence and immunoperoxidase procedures at the light confocal and EM levels, immunogold labeling on ultrathin frozen sections and on sections of tissue embedded with low temperature resins, laser confocal microscopy, and label fracture and freeze-fracture electron microscopy, in situ hybridization, and real time fluorescence imaging of living cells.

2. Cell Culture

The cell culture service of the Cell Biology Core provides individual investigators with technical support, expertise, and resources for the growth of numerous intestinal and other cell lines used in nutritional studies. They are utilized for performing cell biological studies relevant to the study of cellular architecture and function, epithelial cell biology; immunological assessment of inflammatory processes; and providing various plasmid and viral vectors for targeting expression of proteins in various cell compartments, including apical or basolateral surface expression. A major focus of this service of the Core is the application of cell culture as a principal in vitro model to investigate aspects of clinical nutrition. This service provides expert consultation in developing optimal experimental strategies for a specific project, training in specific techniques to enable an investigator to apply them in their laboratory, and long-term training to enable new investigators and fellows to develop a solid knowledge and experience base in cell culture techniques.

3. Immunology

The immunology service of the Cell Biology Core provides NORC investigators with the technical support and expertise to study the role of nutrition on immunologic parameters. The Core provides flow cytometric evaluation of cell populations for phenotypic identification and analysis of intracellular protein expression, and for the production of monoclonal antibodies. The immunology service of the Cell Biology Core is designed to facilitate the work of NORC investigators who are performing nutrition-related research through service, consultation, and instruction in a variety of immunologic methods, such as assay development. This Core provides supervision in established techniques and in emerging immunologic methodologies. The techniques and services provided include: monoclonal antibody production, a shared antibody bank, flow cytometry, high-speed cell sorting, and lymphocyte function assays. Investigators are also assisted to establish collaborations with other investigators to carry out immunology-related aspects of scientific projects.

4. Analytical Glycobiology

A new service of the Cell Biology Core is analytical glycobiology. The analytical glycobiology service provides expertise, reagents, and instrumentation specific to analysis of glycans, primarily cell surface glycans. The goal of this new service of the Cell Biology Core is to isolate, identify, and measure specific molecules of biological interest and to test whether the isolated material has biological activity. These services are complementary to those already offered by the Core, completing the set of technologies available to focus on problems in nutritional science and obesity research.The strength of this Core is the ability to focus a wide array of technologies, including analytical glycobiology, onto a given problem using techniques and resources that might not otherwise be readily accessible to members of the NORC research community. Analytical services include isolation, purification, and analysis of biologically interesting glycans and other molecules using the glycobiology laboratory and its instruments.

5. Training Activities

The Cell Biology Core provides training of key personnel from participating laboratories. Instruction for investigators in cell biology methods occurs at four levels: consultation, short-term supervision of investigators in a specific technique, long-term project development, and the educational enrichment activities described below.

The Cell Biology Core organizes three formal courses of study that encompass the general areas of the Core: 

1) Molecular Cell Biology
2) Glycobiology
3) Nutritional Aspects of Gastrointestinal Immunology

These courses are focused on how advances in these areas can best be applied to research problems in nutrition, intestinal function, obesity, mucosal immunology, and gut development. These courses are open to any member of the NORC, and are particularly valuable for the graduate students and new fellows involved in nutrition research training programs. The Core offers courses of study for 10 weeks of each summer, the topics of which rotate among the following:

Molecular Cell Biology

A comprehensive overview showing how important discoveries from diverse disciplines led to our present understanding of cell biology that forms the basis of modern nutritional sciences. The course reviews basic chemistry, biochemistry, and biology, and its integration into basic biological process and genetic mechanisms of the cell. Cell organization, biochemistry, and intermediary metabolism are reviewed in the context of how these cellular processes are integrated into the systems essential for life. Cell signaling, signal transduction pathways, gene induction and repression, and the integration of multiple signals to control specific genes are put into the context of cellular homeostasis, adaptation to environmental change, pathogenesis, cell cycle and growth, and cell-type specification. Finally, tissue-specific development and its control in higher eukaryotes are related to cancer, infection, and aging.

Glycobiology

The importance of glycan expression for the normal functions of the intestinal mucosa, including mucosal immunology and processes related to digestion, is now becoming more apparent. This course discusses the role of glycans to problems in gut physiology, including digestion, and in the relationships between the mucosal epithelia resident bacteria, including pathogens. Early topics cover general principles in glycobiology, including the biosynthesis, metabolism, functions of glycans, and interactions between glycans and glycan-binding proteins (lectins). The use of methods specific to the analysis of glycan structure and function are reviewed and critiqued. Application of research in glycobiology to problems related to gut physiology, mucosal immunity, gut ontogeny, symbiosis between humans and their microflora, and nutrition are emphasized.

Nutritional Aspects Of Gastrointestinal Immunolgy

This course in nutritional aspects of mucosal immmunology examines the interrelationships that link human nutrition, mucosal immunology and chronic diseases of the gastrointestinal tract. Topics include mucosal response to food antigens, probiotics, interrelationship gut physiology, mucosal inflammation, gut ontogeny, symbiosis between humans and their microflora, the interrelation between nutrition and mucosal immunity, ontogeny of allergic responses, and interaction of developing gut with human milk. This couse provides a solid foundation for advanced research in the nutritional sciences as they relate to mucosal function.

For more information about this core, please contact:

David S. Newburg
Pediatric GI & Nutrition
114 16th Street
Charlestown, MA 02129

Office: 617-726-4169
Fax:    617-726-4172

Email: dnewburg@partners.org

Dr. Newburg’s biographical sketch is linked here.

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Updated 1/25/2008