FY 2005 Congressional Justification

* FTEs: Employment levels measured by full time equivalents

Additional Details - FY 2005 President's Budget Request

This document provides justification for the Fiscal Year 2005 activities of the National Institute of Dental and Craniofacial Disease Research (NIDCR), including HIV/AIDS activities. Justification of the National Institutes of Health (NIH)-wide FY 2005 HIV/AIDS activities can be found in the NIH section entitled "Office of AIDS Research (OAR)."

Introduction

The past decade has profoundly changed how craniofacial and oral health scientists conduct basic research. Rare are the bulky electrophoresis gels or large chromatographic columns that once yielded small, incremental bits of data on a single gene or protein. Now increasingly common are a new generation of sophisticated laboratory tools with a sometimes confusing array of acronyms such as Multiphoton Microscopy (MPM), Polymerase Chain Reaction (PCR), Serial Analysis of Gene Expression (SAGE), and Quadrapole (Q-) - and Matrix-assisted Laser Desorption (MALDI-) Time of Flight ( TOF) mass spectroscopy. These truly revolutionary tools can help researchers rapidly profile thousands of molecules in our cells at once or even those of the pathogens that inhabit our mouths, greatly enhancing the power and the pace of basic research.

This progress in the basic sciences, however, brings unique challenges to craniofacial and oral health science. With so much data being generated throughout the world, how can the field ensure that exciting molecular leads don't end up buried and untested in an online database? How can communication among basic and clinical scientists be enhanced to further accelerate the translation of promising discoveries? And, as more compounds will inevitably enter the clinical-trials pipeline, does an adequate infrastructure exist to prioritize and evaluate each agent in a timely manner?

The NIDCR is now providing the leadership to answer these critical questions. The Institute has taken the lead to invest in technology, computer power, and analytic methods that will allow scientists to rapidly and efficiently mine existing data sets for telltale biological patterns that might not be readily apparent with existing tools.

The Institute will also place a greater emphasis on supporting multi- and interdisciplinary research, hoping to foster increased dialogue among a broader range of basic and clinical scientists and thereby speed the translation of intriguing fundamental discoveries. For example, as described later in this document, clinicians such as dentists, cell biologists, and materials scientists brought their disparate analytical strengths to bear to engineer part of the lower jaw in the laboratory. As this advance indicates, the melding of scientific disciplines will help to unlock the age-old and once impenetrable secrets of human biology, suggesting powerful new approaches to improve craniofacial and oral health.

With the potential for so many new leads in the clinical pipeline, NIDCR also has expanded its clinical trials program, with an emphasis on conducting late-stage, or Phase III, clinical trials. In 2003, the Institute launched two large Phase III clinical trials to evaluate whether treating severe periodontal disease in pregnant women reduces the incidence of preterm births. In the spirit and strength of multidisciplinary research, these studies link dentists, obstetricians, nurses and other health professionals to answer a public health question that none could answer alone. Moreover, if a clear benefit emerges, the intervention would be readily available to the public, relatively inexpensive, and would greatly benefit the nation's public health.

The NIDCR's commitment to so-called "translational" research is highlighted throughout much of the rest of this document. As demonstrated by the examples of scientific advances, and planned scientific initiatives in this document, craniofacial and oral health science is moving closer to a new age of molecular-based medicine that will greatly enhance our ability to prevent and treat oral disease. These examples also offer clear evidence that the nation's wise investment in dental research will continue to benefit Americans for many generations to come.

GENE THERAPY

Gene therapy often has been hailed as the "home run" of biomedical research - the potential answer for devastating diseases such as cancer and diabetes. If we can transplant normal copies of genes into cells with abnormal, disease-causing versions of the genes, the thinking goes, we may be able to cure many acquired diseases and virtually all inherited disorders. However, the promise of gene therapy has been interrupted by a host of technical challenges -- chiefly the challenge of correctly and reproducibly delivering genes to cells in difficult-to-reach internal organs such as the liver or pancreas. Until this problem is solved, the promise of gene therapy will remain elusive. There is tremendous need for innovative strategies to overcome the problem.

Science Advance: Animal Studies Show Promise in Treating Sjögren's Syndrome

A team of NIDCR scientists reported the first successful use of gene therapy to limit salivary gland inflammation and preserve saliva flow in a mouse model of Sjögren's syndrome, an autoimmune disorder that can render people unable to produce saliva or tears. The scientists found that transferring the gene for human interleukin-10 (IL-10) via an adeno-associated virus into the animal's salivary glands reduced inflammation and preserved salivary flow. The treatment worked whether it was started before or after the onset of salivary dysfunction. The scientists noted the results are important because they show that an immunomodulatory gene that is delivered locally to the salivary glands can be effective in limiting the functional damage of the condition. Future studies will seek to understand the molecular changes that preserved salivary function.

NIDCR Initiative: Salivary Gene Transfer - Re-Engineering the Promise of Gene Therapy

For millions of people who suffer from diseases such as type 1 diabetes, growth hormone deficiency, and hypoparathyroidism - conditions caused by a deficiency in a single protein - gene therapy may someday offer an attractive alternative to available treatments. However, researchers have been hard-pressed to reliably deliver genes to vital internal organs such as the liver. A possible solution to these longstanding problems is the salivary glands. These paired organs are easily accessible and have the natural ability to secrete proteins directly into the circulatory system. Recent advances in gene transfer technology now make it possible to efficiently and reproducibly incorporate exogenous genes into salivary glands. In patients with single-protein deficiencies, a transplanted gene will express the deficient protein and provide therapeutic benefit. Gene transfer approaches could also be used to treat craniofacial or oral conditions such as the salivary gland dysfunction resulting from autoimmune disease such as Sjögren's syndrome or irradiation therapy.

In FY 2005, NIDCR will launch a historic initiative to move gene transfer from the laboratory to the clinic by evaluating the safety and efficacy of salivary gland gene transfer in three sequentially staged clinical trials involving: a) patients with adult growth hormone deficiency, b) patients with low levels of the hormone erythropoietin, which can occur in persons with kidney insufficiency, cancers, HIV infection, rheumatoid arthritis, sickle cell disease and ulcerative colitis and c) patients with Sjögren's syndrome and salivary gland damage resulting from irradiation therapy. If successful these gene therapy approaches would provide immense benefit to patients without the potential risks involved in using gene therapy approaches via other internal organs.

PUTTING RESEARCH INTO PRACTICE

To achieve our goal of improved oral health for all people, NIDCR must ensure that research advances are translated and adopted into clinical practice. The NIH Roadmap for Medical Research calls for re-engineering the nation's clinical research infrastructure by creating better integrated networks of academic centers that work with each other and with community-based healthcare providers on clinical research. This new clinical research infrastructure will link communities with community-based practitioners and with academic researchers and facilitate the translation of research results and adoption of knowledge into practice. Participation of dentists in the new clinical research infrastructure is crucial, given that overall health and oral health are inseparable; many systemic conditions such as diabetes, Sjögren's syndrome, HIV/AIDS and osteoporosis have important oral symptoms, manifestations or complications; and emerging evidence suggests oral infections may be risk factors for certain systemic diseases.

NIDCR New Initiative: Oral Health Practice-Based Research Networks

Many of the unique questions faced by dental health professionals on a daily basis are most appropriately addressed in dental practice settings, among unselected patient populations. Practice-based research networks can generate important and timely information to guide the delivery of health care and improve patient outcomes. NIDCR will launch an initiative to create dental Practice-Based Research Networks (PBRNs) to conduct clinical research. In time, linking the oral health practice-based research networks with existing medical networks will provide additional patients, professional expertise, and integration of resources for conducting research across a broad spectrum of health care specialties. By connecting practitioners with experienced clinical investigators, PBRNs will enhance clinical research supported by the NIDCR and produce findings that are immediately relevant to practitioners and their patients. The networks can support a variety of clinical studies with clear and easily defined outcome measures, and they typically draw on the experience and insight of practicing clinicians to help identify and frame the questions. Because research is conducted in the real-world environment of dental practice, the results are more likely to be readily adopted by practitioners.

TISSUE ENGINEERING

Coined in 1987, the term "tissue engineering" combines principles from engineering and the life sciences in a bold attempt to use the body's own biological materials to repair, regenerate, and ultimately replace damaged organs and tissues, including bone and cartilage. If successful, tissue engineering would eliminate the need for bone grafts and avoid problems associated with artificial replacement joints, such as donor site defects, immunorejection, abnormal wear and tear, and transmission of pathogens. Tissue engineering also holds great promise in treating diseases and injuries of the orofacial tissues, which can have a tremendous negative impact on a person's quality of life.

Science Advance: Early Progress in Tissue Engineering Mandibular Condyle

Researchers have long dreamed of engineering new knees, hips and other body joints in the laboratory from a person's own bone and cartilage producing adult stem cells. The challenge has been to figure out how to manipulate these cells and get them to form tissues that precisely mirror the natural three-dimensional structure and mechanical strength of our normal, healthy joints. In an important first step toward realizing this dream, scientists have created a mandibular condyle from rat adult stem cells that is the precise three-dimensional shape of the human joint. A mandibular condyle is the knobbed ending of the lower jaw; it joins the lower jaw to the temporal bone of the skull on both sides of the head at the temporomandibular joint, or TMJ.

Stressing that their findings are preliminary and significant scientific challenges lie ahead, the researchers said the results are hopeful because they produced their structure from a single population of stem cells which were induced to form two distinct layers of bone and cartilage, a characteristic feature of a condyle and a first in the field of tissue engineering. According to the scientists, this work is instructive in learning to engineer not only mandibular condyles but also those of other joints throughout the body.

Science Advance: Engineering Better Tooth Enamel

Dental researchers have long sought to obtain the scientific knowledge to make or modify tooth enamel. This would allow them to help children with inherited malformations, such as amelogenesis imperfecta, and possibly one day to remineralize decayed teeth, an advance that would have broad beneficial public health implications. As the research has progressed, scientists have become increasingly aware that their future success will hinge on manipulating a unique type of protein called amelogenin. What makes amelogenins so unique is, as the predominant protein in the lattice-like matrix upon which enamel forms in the tooth bud, they regulate and contribute to the mineralization process then disappear before the tooth erupts. Previous work in animals has shown that amelogenin embedded in the enamel matrix first must self assemble into its proper shape to regulate the production of enamel. If amelogenin self assembles incorrectly, the structural integrity of the enamel will be flawed. This led a multidisciplinary team of NIDCR supported researchers to take the research an important step further: They knocked out regions of the mouse's amelogenin gene that are involved in the self-assembly process, then analyzed with high-powered imaging techniques the mechanical properties of individual enamel rods. They found the genetic alterations produced inferior enamel that the scientists attributed to structural disorganization in the original assembly of the protein matrix, which arose because of the defective amelogenin. This finding is proof of principle that, by altering the amelogenin gene, it is possible to influence the mechanical properties of dental enamel. This suggests that, by correcting defects in amelogenin self assembly, it is also possible to improve the strength and durability of tooth enamel and provide information useful in learning to remineralize damaged teeth.

Science Advance: Key Discovery in Organ Development

Within weeks of fertilization, one of the great mysteries of life occurs. The heart, lungs, kidneys, and other organs begin to appear in the fetus. Many start out as a tube-shaped sheet of cells, which then bud and branch anew hundreds to millions of times before reaching their final three-dimensional shape. Although scientists have identified many proteins that are present as organs develop, they know little about how these molecules interact to catalyze the process, information that is vital in learning one day to efficiently engineer replacement organs.

A team of NIDCR scientists made a critical discovery that helps to explain in part how the process works. They found that cells in certain areas of the bud secrete the protein fibronectin, which helps to create a deep indentation, or cleft, in the bud. These clefts serve to subdivide the single bud into several smaller buds, freeing them to branch in different directions and form increasingly more intricate, pre-programmed three-dimensional patterns. Intriguingly, the scientists found they could double the rate of branching when they added fibronectin to organ cultures depleted of the protein. They demonstrated their findings in organ culture studies involving the submandibular salivary gland, lung, and kidney. This finding suggests a specific biological mechanism that bioengineers can exploit in future studies to spur the natural growth of many developing organs. Because their discovery occurred in submandibular salivary gland cells, it also highlights the value of studying easily accessible oral tissues.

PAIN

Pain research has now embarked upon an exciting era of basic discovery that seeks to map in greater detail the multiple routes, or pathways, that sensory signals travel en route to the spinal cord and brain. Helping to fuel these studies is the improved ability of researchers to discover and clone protein receptors in the peripheral nervous system. These receptors often serve as the starting point in the transmission of the molecular signals that sound the warning bells that tissue damage has occurred. As scientists learn more about how these receptors process and send information, it will be possible to derive new and more targeted agents for the estimated 50 million Americans who suffer each year from chronic pain.

Science Advance: New Insight into Pain Response

As the careers of Michael Jordan, Lance Armstrong, and other great athletes attest, there is tremendous variability in how people respond to pain. One of the many possible explanations is the subtle variation written into genes encoding proteins that process pain signals. An excellent example is the COMT gene, which produces a substance that metabolizes catecholamines, a modulator of certain nerve chemicals that signal pain. NIDCR supported researchers have shown that people with subtle variations in the COMT gene tended to feel and report a higher level of pain, are less adept at modulating their responses to sustain pain and experience a more negative emotional state than those without those genetic changes. The researchers also showed that people with the genetic variations had diminished regional responses of a certain receptor system that has been shown to enhance a person's tolerance of pain. Knowledge of how the COMT gene influences how people experience pain, and further understanding of the genetic factors that may underlie individual differences in adaptability to pain and other stressful stimuli are critical in designing targeted drugs to help people efficiently manage pain and their susceptibility to it.

NIDCR New Initiative: Mapping the Mechanisms of Orofacial Pain

The NIDCR will begin an initiative to define the proteins and protein networks involved in processing nociceptive information in the orofacial region. The initiative encourages interdisciplinary studies that employ genomic and proteomic approaches, imaging technology, and computational biology to clarify the molecular events involved in chronic orofacial pain disorders. Specific areas of emphasis include: 1) acute orofacial pain, 2) the transition from unrelieved acute to chronic orofacial pain, 3) neuronal hyperexcitability, and 4) orofacial pain disorders of inflammatory and neuropathic origins. An improved understanding of the molecular mechanisms underlying pain processes could lead to effective therapeutic interventions for chronic pain conditions.

DENTAL CARIES

While there has been a sharp reduction in once rampant dental caries - more commonly known as tooth decay -- caries is still the most common chronic childhood disease-- five times more common than asthma and seven times more common than hay fever. Moreover, the burden of dental caries in terms of both extent and severity has shifted dramatically to a subset of our population. Though few Americans avoid caries altogether, approximately a quarter of the population now accounts for about 80 percent of the disease burden. Dental caries remains a significant problem for vulnerable populations of children and people who are economically disadvantaged, elderly, chronically ill, or institutionalized.

Science Advance: Defining Bacteria Involved in Childhood Caries

As long as many dental researchers can remember, Streptococcus mutans has been labeled the prime suspect in causing dental caries (tooth decay). But as scientists have learned more about the bacterial community in which S. mutans resides, they have come to appreciate that no bacterium acts alone. Oral bacteria, of which over 500 varieties are known, tend to aggregate with other species in symbiotic relationships that allow each to adapt more readily to the constant stresses and strains of life inside the mouth. Using sophisticated molecular techniques, NIDCR-supported researchers are uncovering which oral bacteria might assist or otherwise be involved along with S. mutans in causing dental caries. They found eight species of bacteria that are correlated with varying degrees of tooth decay including specific bacteria that may have a critical role in initiating caries and another that may play a role in severe caries (as measured by the depth of the lesion). This study also found specific bacteria associated with good oral health. As part of the study, the researchers found ten novel or previously uncultivated species of bacteria, each of which merit further investigation as potential pathogens. These findings suggest several different targets that could be pursued to better prevent tooth decay.

Science Advance: Race, Ethnicity, and Early Childhood Caries

By 2050, it is estimated that about half of the U.S. population will consist of African Americans, Asians, Hispanics, American Indians, and other current minority populations. The document Oral Health in America: A Report of the Surgeon General noted that "Currently available data for these groups present a picture of disease that is generally poorer than that for non-Hispanic whites. These sub-groups present a unique cluster of health, socioeconomic, and cultural issues. At the same time, data for the subgroups within each of these categories are lacking." To begin generation of this data, a group of NIDCR grantees and colleagues compared the possible association between race/ethnicity and early caries among two groups of children: one enrolled in the California Head Start program, the other consisting of preschool children who were not involved with the Head Start. In this study of 2,520 children, the researchers found that 33 percent of Asians and 33 percent of Hispanics enrolled in the Head Start program had early childhood caries, the largest prevalence of among all races/ethnicities. In fact, the estimated risk for childhood caries was more than three times higher among Asians in Head Start compared to white and black children in preschool. The team also reported that a little under three fourths of the Hispanic children in both groups had a history of falling asleep while sipping milk or a sweet substance, a risk factor for early childhood caries. With these baseline data, it is possible to further compare the role of race/ethnicity in early childhood caries in children living in other regions in the country and to design more targeted prevention strategies to ensure that Americans of all cultures can be free from this disease.

PERIODONTAL DISEASES

It is estimated that 80 percent of American adults have some form of periodontal disease, bacterial infection of the mouth's "periodontium." The periodontium consists of the gingiva, or gums, the ligament that attaches the tooth to the bone, the hard tissue covering the roots and the bony sockets surrounding the teeth. Although periodontal diseases are non-life threatening, they can be chronic, expensive to treat, and greatly reduce one's quality and enjoyment of life. Years of research have established that specific types of bacteria such as Porphyromonas gingivalis plays a major role in the initiation and progression of severe forms of periodontal disease. However, much still remains to be learned about the biology and behavior of this destructive oral bacterium.

Science Advance: Genome of Oral Pathogen Fully Sequenced

NIDCR-supported scientists have finished sequencing the genetic material of P. gingivalis , marking the third oral pathogen to have its DNA fully sequenced. The organism's genetic material consists of 2.3 million bases, or units, of DNA and contains 1,990 open reading frames, or possible genes. Because of this accomplishment, scientists throughout the world now will be able to access an online database containing the full sequence of this bacterium. It will allow them to scroll through the tables of information, form hypotheses, and rapidly test their theories in the laboratory. Not only will this genetic blueprint accelerate investigation into the causes of periodontal disease, it also will suggest points of weakness in the bacterium's life cycle that might be exploitable in the future to prevent or control this oral pathogen. At the same time, given the purported link between this P. gingivalis and heart disease, the full sequence will be a helpful tool in understanding the biology of this bacterium as future studies progress.

Science Advance: Animal Studies Support Periodontal and Heart Disease Link

Ever since a link between periodontal disease and heart disease was first tentatively proposed nearly 25 years ago, a large body of experimental evidence has accumulated in support of the possible association. Among the most recent data is a study showing that a type of mouse prone to coronary heart disease developed signs of atherosclerosis at an accelerated rate upon receiving weekly intravenous injections of Porphyromonas gingivalis , an oral bacterium strongly linked to periodontal disease. However, some questioned whether the study advanced the scientific debate because P. gingivalis had been introduced into these animals by artificial means. They said the data, while interesting, left unanswered the real question: Can P. gingivalis from the mouth enter the bloodstream of these mice and play a role in causing atherosclerosis?

A team of NIDCR grantees has answered the question in the affirmative. After establishing oral infections with P. gingivalis in the same type of mouse, they found an increase in atherosclerotic plaques within four months compared to uninfected control mice. The plaques were about 40 percent greater in size than those in the controls, and the affected mice showed classic indications of an increased immune response and coronary inflammation. Interestingly, in two of nine mice infected with P. gingivalis , DNA from the bacterium had localized within the aortic tissue.

This study presents the first experimental evidence that orally administered P. gingivalis can exacerbate the formation of arterial plaques. Through further research with this mouse model, it may be possible to begin to pin down precisely how the bacterium contributes or perhaps directly causes the problem. But, more immediately, their data support previous epidemiologic data suggesting a linkage between periodontal disease and heart disease.

HIV/AIDS

HIV infection is a major public health problem throughout the world. The hallmark of this infection is a gradual depletion of CD4+ T cells that eventually leads to a state of immune suppression. This immune suppression predisposes the patients to warts, pre-malignant oral lesions and oral cancers. Some of these cancers are aggressive, hard to treat and can be detrimental to the quality of life of persons with HIV infection. The biological basis for AIDS-related oral lesions is not yet clear. There appears to be an emerging role for various concurrent viral infections in the HIV-infected host that are likely implicated in the pathogenesis of these ailments. The oral cavity represents an environment conducive to infection with multiple pathogens, yet appears resistant to others, providing a unique opportunity to define the underlying mechanisms by which the oral mucosa discriminates among infectious micro-organisms. More research on the uniqueness of the oral mucosa, compared to other mucosal surfaces will provide much needed information to enhance the protection of mucosal tissues against HIV infection.

NIDCR New HIV/AIDS Initiatives

NIDCR will support several initiatives to address HIV infection. The first will stimulate research to improve our understanding of the biological basis of development and progression of AIDS-related oral cancers and tumors, and to encourage research identifying novel targets for treatment, and biomarkers for early diagnosis and monitoring of disease progression. Such research has the potential to significantly improve the quality of life of patients affected by oral malignancies and tumors experienced by up to 25 percent of patients with AIDS. Secondly, NIDCR will promote research that will lead to the development and validation of a practical and physiologically relevant in vitro model of the oral mucosa that can be used to study HIV infection and the complications associated with AIDS under highly controlled conditions. It is envisioned that the availability of such an in vitro oral mucosa system will provide opportunities to substantially enhance the fundamental understanding of oral HIV infections. NIDCR is also encouraging studies to examine the structure, biology, genetics, physiology and biochemistry of the oral mucosa and to compare these features with other mucosal surfaces, especially vaginal and rectal mucosa, in regard to susceptibility or resistance to HIV infection and replication. Lastly, NIDCR is launching an initiative to encourage multidisciplinary research on the oral complications of HIV infection and their prevention that crosses several scientific disciplines (e.g., virology, immunology, cell biology, pathology, epidemiology, biochemistry, pharmacology, medical imaging, etc.) A multidisciplinary approach to address the oral complications of HIV infection is timely and will expedite and increase our knowledge of the field as well as provide new insights and solutions to an ever-growing list of unanswered questions that continue to emerge.

NIH ROADMAP

The NIH Roadmap for Medical Research will provide knowledge to facilitate and accelerate several NIDCR Initiatives. Some examples are as follows:

• The Roadmap's New Pathways to Discovery- in particular the initiative Building Blocks, Biological Pathways and Networks - seeks to create a better "toolbox" for researchers that include innovative ways for capturing real-time images of molecular and cellular events that occur in the human body. The scientific goals of this initiative are closely linked to NIDCR's molecular anatomy efforts to identify the full complement of genes, proteins and protein networks that are expressed in both oral cancer and periodontal disease. Advances in proteomic analysis platforms will be crucial for NIDCR to achieve its goal of defining the salivary proteome - a critical step in the Institute's long-term goal to exploit the salivary secretions for diagnostic purposes. The Molecular Libraries and Molecular Imaging initiative holds great promise for accelerating NIDCR's progress in defining the molecular pathways of pain reception and in elucidating new therapeutic targets to manage chronic pain. The availability of more robust molecular libraries and facile screening assays will revolutionize our ability to dissect the complex cascade of molecular events responsible for the development of the craniofacial complex, using a chemical genomics approach.

• The Roadmap Initiative Research Teams of the Future will stimulate new mechanisms to facilitate the conduct of multi- and interdisciplinary research. NIDCR's work particularly in areas such as Sjögren's syndrome, cleft lip and palate, ectodermal dysplasia, cancer, chronic pain and infectious diseases has traditionally included researchers from many disciplines such as immunology, microbiology, neurobiology and pain research. Ongoing studies, designed to determine the linkages between oral infections and systemic conditions such as preterm birth and cardiovascular events have required collaborations among physicians, dentists and nurses. By integrating several disciplines and their approaches in a more sustained and systematic way, this roadmap initiative will enable NIDCR's ongoing inter- and multidisciplinary efforts to further expand and develop new ways to approach research questions. For example biological engineering may one day provide the nanotools required to switch pain signals off in chronic pain situations or dysregulate the quorum sensing required to form dental biofilms.

• The Initiative on Re-engineering Clinical Research will promote the creation of better integrated networks of academic centers working on clinical research that include community-based health care providers. The integration of dentists in this new clinical research infrastructure is key given that overall health and oral health are interrelated and that certain systemic conditions such as diabetes, Sjögren's syndrome, HIV/AIDS and osteoporosis have important oral symptoms, manifestations or complications. NIDCR is creating an oral health practice-based network to support research that answers questions facing dentists in the routine care of their patients and that accelerates the transfer of research findings into practice. In time, linking the oral health practice-based research networks with existing medical networks supported through the roadmap initiative will provide additional patients, professional expertise, and integration of resources for conducting research across a broad spectrum of health care specialties.

Budget Policy

The Fiscal Year 2005 budget request for the NIDCR is $394,080,000, an increase of $11,032,000 and 2.9 percent over the FY 2004 Final Conference Level. Also included in the FY 2005 request, is NIDCR's support for the trans-NIH Roadmap initiatives, estimated at 0.63% of the FY 2005 budget request. This Roadmap funding is distributed through the mechanisms of support, consistent with the anticipated funding for the Roadmap initiatives. A full description of this trans-NIH program may be found in the NIH Overview.

NIH's highest priority is the funding of medical research through research project grants (RPGs). Support for RPGs allows NIH to sustain the scientific momentum of investigator-initiated research while providing new research opportunities. The FY 2005 NIH request provides for an aggregate 1.3 percent increase in average cost for Research Project Grants, consistent with the Gross Domestic Product deflator. The NIDCR is providing an average cost increase of 1.9 percent for direct recurring costs in noncompeting continuation awards. Competing RPGs are based on an average cost increase of 1 percent.

Advancement in medical research is dependent on maintaining the supply of new investigators with new ideas. In the Fiscal Year 2005 request, NIDCR will support 330 pre- and postdoctoral trainees in full-time training positions. Stipend levels for pre-doctoral and post-doctoral recipients supported through the Ruth L. Kirschstein National Research Service Awards will remain at FY 2004 levels.

The Fiscal Year 2005 request includes funding for 12 research centers, 140 other research grants, including 22 clinical career awards, and 14 R&D contracts. Intramural Research and Research Management and Support receive increases to support increased pay and estimated inflationary increases in FY 2005.