Intramural Research Overview

Research

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducts and supports basic biomedical research and training related to diabetes mellitus; endocrine, bone, and metabolic diseases; digestive diseases, including liver diseases and nutritional disorders; and kidney, urologic, and hematologic diseases. More than 85 percent of the Institute's budget is allocated to its extramural program, which supports research and training of scientists in medical schools, universities, and private research institutions across the Nation. The NIDDK's Division of Intramural Research conducts research and training within the Institute's laboratories and clinical facilities in Bethesda, Maryland, and in Phoenix, Arizona. NIDDK's intramural programs are evaluated periodically by an independent Board of Scientific Counselors.

The hallmarks of the NIDDK Intramural research program are excellence and diversity. Many of the staff of the NIDDK Division of Intramural Research have achieved international recognition as highly productive and innovative scientists. The present program continues a tradition of excellence reflected in the several Nobel prizes and other prestigious awards that have resulted from its work. Many scientists trained in the intramural research program of the Institute are now prominent faculty members at leading universities throughout the world.

The research conducted in the intramural program spans the breadth of modern biomedical investigation, from basic science to clinical studies. A sampling of some areas under study includes: a) structural biology with outstanding groups in both x-ray crystallography and NMR spectroscopy performing pioneering studies; b) chemistry with several excellent laboratories involved in synthesis and characterization of novel compounds, including neuroactive substances and naturally occurring toxins; c) molecular biology, particularly studies of chromatin structure and function, and studies of DNA recombination; e) developmental biology using model systems ranging from slime molds to vertebrates; f) signal transduction, including basic and human disease-oriented studies of insulin and insulin-like growth factors and their receptors, GTP-binding proteins and GTP-binding protein-coupled receptors, and thyroid and steroid hormone receptors.

NIDDK intramural training opportunities are as diverse as the research conducted within the intramural program. Training in several basic science disciplines such as molecular biology, biochemistry, pharmacology, and cell biology may be obtained in many of the Institute's Labs and Branches. There are clinical training opportunities in gastroenterology and liver disease, and in endocrinology, genetics, and hematology. Unique training opportunities exist in the Institute's Epidemiology and Clinical Research Branch in Phoenix, Arizona, which conducts studies on the Pima Indians, a population with an extraordinarily high incidence of diabetes and obesity.

Training in the NIDDK intramural program offers the opportunity to learn from some of the world's outstanding scientists, and to contribute to the important discoveries being made by them. The following lists just a few examples of recent research accomplishments by NIDDK intramural scientists:

• Development of pioneering methods for determination of 3D structure in solution of proteins by NMR techniques.
• Determination of 3D structure of tryptophan synthase, a multienzyme complex, and of HIV integrase.
• Discovery of method for formation of triplex DNA at any site in the human genome, leading to abilities to cleave selectively any genomic fragment.
• Identification of genetic components in both human obesity and Type II diabetes.
• Expression of proteins of therapeutic relevance in milk of transgenic mammals.
• Discovery of insulin receptor mutations in syndromes of extreme insulin resistance.
• Discovery of endogenous benzodiazepines as the basis for hepatic encephalopathy.
• Identification by positional cloning of the multiple endocrine neoplasia type 1 tumor suppressor gene causing inherited and sporadic forms of parathyroid and other endocrine neoplasia.
• Identification of genetic defects in most common forms of Tay-Sachs Disease and generation of knockout mouse model.
• Identification of mutations in signal transducing "G proteins" in various human diseases.
• Identification of mutations in the vasopressin receptor in X-linked nephrogenic diabetes insipidus.
• Identification of activating mutations of the luteinizing hormone receptor as the cause of familial male precocious puberty.
• Use of adeno-associated parvovirus as vector for human gene transfer and basic studies on mechanism of site-specific chromosomal integration of this virus.
• Expression of human recombinant thyroid stimulating hormone for use in evaluation of thyroid cancer.
• Identification of genes encoding major zona pellucida proteins with implications for fertility and contraception.
• Use of hydroxyurea and erythropoietin in treatment of sickle cell anemia.
• Use of interferon and other cytokines in treatment of various forms of hepatitis.
• Use of H2-histamine receptor blockers and hydrogen ion transport blocker in treatment of forms of ulcer disease associated with gastric acid hypersecretion.
• Cloning of receptors for peptides such as cholecystokinin involved in satiety and regulation of the GI system.
• In vitro reconstitution of immunoglobulin gene rearrangement.

As impressive as these recent accomplishments are, the vitality of the NIDDK intramural program and the increasingly powerful tools of modern biomedical investigation promise even more significant future accomplishments. In structural biology, newer NMR techniques promise to reveal the three-dimensional solution structure of even larger proteins. As the complexities of intercellular communication become better understood, one can anticipate further insights in pathophysiology of human diseases including cancer. Studies on gene expression and developmental biology, on vectors for gene transfer, and on gene targeting and recombination promise exciting results with possible application to gene therapy of human disease. Training in the intramural NIDDK research program offers each trainee the challenge and the opportunity to participate in the exciting discoveries of the future.

Campus

With the exception of the Phoenix Epidemiology and Clinical Research Branch in Arizona, the laboratories and offices of the NIDDK intramural program are located on the 300-acre campus of the National Institutes of Health in Bethesda, Maryland a suburb of Washington, D.C. More than 40 buildings house the laboratories and research support services that are shared among the NIH Institutes. The research support facilities include the Clinical Center, the world's largest research hospital, and the National Library of Medicine, the largest repository of medical literature in the world.

As the largest biomedical research facility in the world, NIH attracts scientists from around the nation and the globe who come to give lectures and conduct research. The collegial ambience at NIH helps foster an unequalled environment of intellectual stimulation and exchange. Few researchers could name a more unique and wonderful environment for biomedical discovery. It is no coincidence that seven Nobel Prizes have gone to current or former NIH intramural scientists, including former NIDDK intramural scientists Drs. Martin Rodbell, Christian Anfinsen and Marshall Nirenberg.

Last Update: 8-9-2004