Gary Keith Beauchamp, PhD - US grants

Sodium intake in our society averages 20-40 times the physiological requirement. The excess intake, usually as NaCl (salt), is due in part to the sensory pleasure associated with the taste of salt in foods. The proposed studies are designed to delineate the role played by high and low levels of dietary salt in shaping of preferences for salty food. This research will provide insight into how taste regulates salt intake and will also provide valuable information for those wishing to reduce sodium intake. Two studies with adult volunteers will investigate taste response following alterations of dietary sodium. In the first study, the temporal course of changes in pleasantness and intensity judgments of salty taste during hospital-controlled diets with moderate or low levels of sodium will be investigated. Previous studies indicated that a biphasic response to dietary sodium reduction may occur with pleasantness of salty foods first increasing and then later decreasing. Perceived intensity followed an opposite course. This hypothesized biphasic response will be tested directly. In the second study, subjects will be placed on controlled high salt diets where supplemental salt is added either to food and therefore tasted, or taken in capsule form. Pilot studies indicated that taste changes follow increases in salt intake, perhaps mimicking events leading to high salt preference. The pilot work will be extended to investigate hypothetical mechanisms. In the third study, the role of oro-sensory and/or internal receptors in short-term control of human salt appetite will be examined. All three studies will evaluate the role of salivary sodium in taste changes. The fourth study will examine the development of salty food preference in infants and the role dietary experience plays in its ontogeny. Finally, studies will be conducted to develop an appropriate animal model of human salt preference. Eventually, the model will be used to investigate the role of dietary exposure to salt on salt taste preference.

health science research support; health /scientific organization;

The Monell Jefferson Chemosensory Clinical Research Center (CCRC) involves a collaboration between scientists at the Monell Chemical Senses Center and physicians at Thomas Jefferson University. Collaborative projects also exist with physicians and scientists at the University of Pennsylvania and the Veterans Affairs Medical Center of Philadelphia. The CCRC is devoted to the scientific examination of clinical disorders in taste, smell, and chemical irritation, as well as to basic research in the chemical senses in humans. Through the multi- disciplinary study of clinical populations, CCRC scientists expect to characterize and understand the etiologies of disorders in chemosensory function, provide information on mechanisms and functions of the chemical senses in humans, and develop strategies for treating/coping with chemosensory disorders. The purposed renewal of the CCRC will comprise an Administrative Core unit, a Sensory Core unit (which oversees the evaluation of referred patients with primary complaints of chemosensory disorders as well as refer patients to specific Projects), an three individual research projects. The general aims of the CCRC are: 1) to continue to provide a clinic facility for the evaluation of chemosensory disorders and the study of their etiologies and prognoses, with special emphasis on follow-up of patients and evaluating the quality of life of individuals with chemosensory disorders; 2) to continue to study human olfactory function at the cellular level, applying sensitive electrophysiological and biophysical techniques to human biopsy material collected from healthy young adults and aged individuals, and from patients with neurodegenerative diseases; 3) to increase our understanding of the role of peri-receptor events in the dynamic process of olfactory adaptation and recovery in patient and non-patient populations; 4) to continue unraveling the relationships between intranasal chemesthesis and olfaction, using referred anosmic patients and those with normal olfaction as experimental subjects.

biomedical equipment purchase;

The Monell Chemical Senses Center is seeking exploratory funds to plan for full development of a National Multi-Purpose Research and Training Center for taste and smell. Many of the features of an RTC as envisioned by NIH are already in place at Monell. The exploratory grant will be used to develop programs to strengthen and integrate aspects of Monell's activities to enable it to readily assume the functions of an effective RTC. In basic and clinical research, exploratory funds will be used to initiate feasibility studies of the biochemistry of human olfactory and taste receptor cells. This will provide a needed bridge between Monell's expertise in cellular mechanisms of chemoreception and clinical research on taste and smell. The focus of research training will be expanded for three groups in particular: senior-level scientists/clinicians, post-secondary community college students, and high school students. Using a multidisciplinary approach, strengthened recruitment and training directed toward these groups will have significant potential for contributions to chemosensory research. Exploratory funds will be used to develop a long-needed continuing medical education package for improving awareness and understanding of the chemical senses and their disorders. This will include assessment of the extent and nature of the need for a CME course on the chemical senses, development of a prototype program, and production and evaluation of the program. There is widespread interest in more information about taste and smell from both the general public and the professional community. Exploratory funds will be used to develop vehicles to inform a variety of audiences about the chemical senses, their disorders, potential treatment, and resources available for evaluation. A pilot project to develop and test a brochure targeted to the elderly also will be carried out, in order to provide a model for subsequent implementation of other information dissemination products. An additional activity will be to explore the feasibility of an epidemiological evaluation of chemosensory disorders.

The Monell-Jefferson Chemosensory Clinical Research Center (CCRC) involves a collaboration between scientists at the Monell Chemical Senses Center and physicians at Thomas Jefferson University. Collaborative projects also exist with physicians at the Medical College of Pennsylvania, Wills Eye Hospital and the Veterans Affairs Medical Center of Philadelphia. The CCRC is devoted to the scientific examination of clinical disorders in taste and smell, as well as to basic research in the chemical senses. Through the multidisciplinary study of clinical populations, CCRC scientists expect to characterize and understand the etiologies of disorders in chemosensory function, provide information on mechanisms and functions of the chemical senses in humans, and develop strategies for treating/coping with chemosensory disorders. The proposed renewal of the CCRC will comprise an Administrative Core unit, a Sensory Core unit (which oversees the evaluation of referred patients with primary complaints of chemosensory disorders), and five individual research projects. The general aims of the CCRC will be: 1) to continue to provide a clinic facility for the evaluation of chemosensory disorders and the study of their etiologies and prognoses, with a specific focus on distortion syndromes (dysosmia and dysgeusia); 2) to study normal and abnormal human olfactory function at the cellular and molecular levels, applying sensitive electrophysiological, biophysical and molecular biological techniques to human olfactory biopsy material; 3) to identify non-invasive indices for salt sensitivity and to develop effective dietary intervention strategies for individuals at risk for hypertension; 4) to initiate studies of the nature and physiological bases of drug-related taste dysfunction, with focus on disturbances in oral sensory perception associated with the use of carbonic anhydrase inhibitors; 5) to continue to explore the functional characteristic of, and individual variations in, nasal trigeminal stimulation in both normosmic and anosmic individuals; and 6) to evaluate the relationships between the metabolic disorder trimethylaminuria and chemosensation, examine the biochemical basis of this disorder and explore the molecular genetics of the biochemical defect.

[unreadable] DESCRIPTION (provided by applicant): The ability to detect, and the innate liking for, sweet-tasting compounds presumably arose in animals to insure an adequate intake of calories and other nutrients. However, excess consumption of some sweet substances by humans has been implicated in a number of health disorders. The mechanisms by which sweeteners are detected and their intake regulated remain unclear although much progress has recently been made. In this project, primarily employing the inbred mouse as a model system, we use behavioral, physiological and molecular biological techniques to further our understanding of factors regulating sweetener perception and ingestion. Recently, we fine-mapped one genetic locus, Sac, to a small region of mouse distal chromosome 4 where we and other investigators have now identified a gene that codes for a sweet receptor. Yet a number of lines of evidence indicate that other genes that may specify additional receptors, transductive elements or central nervous system structures must be involved in determining sweet taste perception, preference and intake. During the project period, we will use a number of tools, some of them newly available, to locate and eventually identify novel genes important in regulating perception and intake of sweeteners. The results of this work will further understanding of sweetness perception, the sense of taste, and sensory biology.

9728787 Yamazak There is considerable indirect evidence that the Major Histocompatibility Complex (MHC) of genes a highly variable string of about 50 genes intimately involved in immune recognition also acts to provision individuals with a unique odor (an odortype) analogous to a fingerprint. The objectives of this project are threefold: I) to obtain direct evidence for this investigating odortypes of inbred mice that have targeted gene disruptions ( knockouts ) of one or both of two classes of MHC genes; ii) to investigate the functional role of odortypes in the context of mother- infant interactions;ii) to determine whether the odortypes of the fetus, which is expressed in the secretions and excretions of the pregnant animal, alters the way other animals interact with her. Broadly, the goals of this work are to increase our understanding of how and to what end MHC genes, best known for functioning in immune self-nonself recognition (the genes that must closely match successful organ or tissue transplants), code for individuality of odor. This understanding will through light on how diversity of this gene complex is maintained in nature, how individuals, be they mice or people, recognize each other as individuals and even, on a more practical level, on how dogs are able to track individuals humans. Thus, this project ranges from molecular biology to population biology to forensics.

Body odor plays a prominent role in regulating social, sexual and endocrine responses of many species and specialized structures have evolved to produce and detect odorous signals. Individual recognition, often communicated through body odors, can be critical in mate choice, parental care, and inter-individual interactions. The goals of this project are to better understand how odors signify individuality and in what contexts individual signals modulate social behavior.

The central idea underlying this project was articulated 25 years ago: Perhaps the same set of genes that code for individual identity in the immune system (i.e. those genes that insure rejection of foreign tissue and organ transplants) also provide an animal with a unique odor. These genes, termed Major Histocompatibility Complex (MHC) genes, form a linked set in most vertebrates and they include the most polymorphic of any known genes. They are also involved in coding for individuality of odor (providing each animal with what we have termed an odortype) as has been demonstrated in studies with mice, rats and humans.

The current project explores three aspects of odortypes using the inbred domestic mouse as the model organism. First, studies conducted in the previous funding period documented the role of MHC odortypes in familial interactions. Maternal mice retrieve pups preferentially according to their MHC type and, reciprocally, pups are attracted to familial MHC odortypes. Studies in this project will investigate the roles of pre- and post-natal learning in modulating preference. Prior studies also demonstrated, for the first time in any species, that fetal odortypes are expressed in maternal odors and that the MHC type of the fetus may modulate adult male and female behavior. Studies described in the second part of the current proposal will investigate how experience with fetal odor influences subsequent behavior of the mother and the pup itself after birth. The third part of this project begins an exploration of a novel aspect of odor signaling between individual animals. Both male and female mice that are infected with mouse mammary tumor virus, a virus that causes mammary tumors in females following one or more pregnancies, develop a distinctive odor in the absence of tumors. Studies designed to explore the behavioral consequences of this observation will open a novel area of research.

In sum, this multidisciplinary project links immunology, odors and olfaction, behavior, and disease to advance our understanding of the regulation of social behavior of mice and, by extension, other social mammals. It will also shed light on mechanisms underlying the maintenance of genetic diversity in MHC and other genes.

This research program will continue to benefit from technical assistance provided through the Monell Chemical Senses Center's minority high school and college program. This program, which employs students from schools throughout the greater Philadelphia area including Camden, NJ, will provide training at Monell to over 40 students in the summer of 2001. It is funded by a major grant from the Annenberg Foundation as well as from other sources including institutional funds. We expect, as has been the case in the past years, two minority students per year from this program will work on this NSF project.

[unreadable] DESCRIPTION (provided by applicant): [unreadable] Expansion of the Monell Chemical Senses Center (MCSC), chartered in 1968 as a non-profit scientific research institute, is today the world's leader in basic and clinical studies of the chemical senses: taste, olfaction and chemical irritation. National Institutes of Health (NIH) estimates that in the United States of America (USA), alterations or loss of the chemical senses can be severe enough to have six million individuals seek medical attention during their lifetime. The Center's only building is now completely occupied, limiting the steady growth that has been characteristic of the organization. Two programs showing significant growth - molecular biology and human sensory perception currently have highly productive investigators who have multiple NIH awards with no laboratories available for new staff nor for expansion of existing projects. In order to further an understanding of the chemical senses and expand the Center's research outlook, this application seeks funds to: 1) renovate space to create an 7,200 sq. ft. facility for Chemosensory Molecular Genomics and Proteomics; 2) expand by 7,200 [unreadable] sq. ft, and renovate the Center's Human Chemosensory Research Facility; and 3) provide adequate heating, ventilating, and air-conditioning systems to support the critical needs of these research endeavors. The Center is a unique, focused entity devoted exclusively to outstanding biomedical and behavioral research and training. This proposed expansion will strengthen the institute, improve public health, and benefit a large cross-section of the scientific community. Four million dollars in National Center for Research Resources (NCRR) funding, matched by more than $4 million in Monell funding, are requested to construct a Chemosensory Molecular Genomics and Proteomics Facility and a Human Chemosensory Research Facility. [unreadable] [unreadable]

Institution; Leadership; Medical center; Monitor; Operation; Operative Procedures; Operative Surgical Procedures; Principal Investigator; Programs (PT); Programs [Publication Type]; Scientist; Surgical; Surgical Interventions; Surgical Procedure; Universities; Veterans; fundamental research; programs; surgery

Abstract Leading health organizations around the world, both governmental and non-governmental, have recommended substantial reductions in consumption of simple sugars, in particular added sugars, to enhance human health. Unfortunately, due in large measure to the profound taste appeal of sweet foods and beverages, recommendations to reduce sugar intake have met with little or no success. An alternative approach to support a population-wide reduction in sugar consumption is to reduce added sugars in commercially available foods and beverages with the expectation that people would acclimate over time, such that reduced sugar products eventually become more palatable or even preferred. This approach arises from work on salt taste perception which has demonstrated that when people adopt an entire diet lower in sodium they gradually adjust over a two to three month period and actually come to prefer lower levels of saltiness. These findings formed the basis for an Institute of Medicine recommendation that the food industry gradually reduce salt in manufactured and restaurant food. The FDA and other governmental organizations worldwide support this approach to sodium reduction, and have taken steps to implement it. Would a similar approach work to decrease sugar intake? Unfortunately, very few controlled studies have assessed how sugar and sweetness in the diet affect perception and preference for sugar. Accordingly, we lack the data needed to convince government and industry stakeholders that people will acclimate to low sugar diets like they do to low salt diets. This project will determine whether such changes in sweet taste perception and preference follow reductions in dietary intake of added simple sugars. In this comprehensive clinical trial a USDA nutrition laboratory will supply all the foods and beverages that volunteers will consume over a period of three months. Healthy adults will be randomly assigned to one of four diet conditions. After a baseline month to establish normal sugar intake, Group 1 will receive a diet that is low in added simple sugars relative to the baseline month. For Group 2, sugar intake will be similarly reduced, but the reduction will occur gradually over the three-month diet manipulation. For Group 3, dietary sugar will be reduced as in Group 1, but sweetness exposure will be maintained using non-nutritive sweeteners. Group 4 (control) will not change intake of added simple. Data obtained will allow us to test the central hypothesis of this work: Reduction in sensory exposure to sugar alters sweet taste perception such that reduced sugar foods retain their palatability. Data supporting this hypothesis will in turn increase confidence that a strategy of population-wide sugar reduction will be tolerated by consumers and that it will accomplish a health-benefiting reduction in added simple sugar intake. Secondary outcomes of this work will address a potential sugar intake biomarker, effects of intake of sweeteners, primarily non-nutritive sweeteners, on the human gut microbiome, the hormonal effects of reduced sugar intake, as well as several other variables.