2011 — 2013 |
Mainland, Joel D |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Variability in the Human Odorant Receptor Repertoire @ Monell Chemical Senses Center
DESCRIPTION (provided by applicant): Humans have approximately 400 functional olfactory receptors, but among this set there are a large number of variations between individuals. In some cases, these variations cause a receptor to be nonfunctional in a subset of the population. These variations likely underlie inter-individual variation in olfactory perception. Here we propose to identify ligands for odorant receptors, generate a library of odorant receptor variants and determine how responses to odorants are altered in the variants. The data generated in this proposal will be a critical step in our long-term goal to probe olfactory perception in humans by examining the perceptual correlates of these natural receptor variations. These studies lead to the hypothesis that variability in olfactory perception is caused in part by genetic dysfunction of olfactory receptors and that understanding the links between olfactory receptor variation and receptor function will reveal the underlying logic of the human odor code. To test this hypothesis, two specific aims are proposed: Specific Aim 1: Identify ligands for odorant receptors with segregating polymorphisms Specific Aim 2: Characterize the in vitro function and expression of common odorant receptor alleles. The proposed experiments further our long term goals to understand the logic of odor coding in humans.
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2013 — 2017 |
Mainland, Joel D |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Perceptual Effects of Genetic Variation in Human Odorant Receptors @ Monell Chemical Senses Center
DESCRIPTION (provided by applicant): The sense of smell is an early warning system for the detection of environmental hazards such as spoiled food, natural gas leaks, smoke, or airborne pollution. Smells also play an important role in quality of life, imparting the flavor of foods and beverages. The long- term objective of this proposal is to understand the nature of odor coding at the receptor level. Currently, little is known about how changes in the receptor activation pattern alter olfactory perception. In the research proposed here, we use next-generation sequencing techniques, heterologous expression systems, and human psychophysics to understand the links between receptor genotype, receptor function and olfactory perception. Learning the rules for transforming receptor activity into perception will advance our understanding of odor coding.
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2018 |
Barlow, Linda A (co-PI) [⬀] Mainland, Joel D Munger, Steven D (co-PI) [⬀] |
R13Activity Code Description: To support recipient sponsored and directed international, national or regional meetings, conferences and workshops. |
Emerging Strategies For Treating Chemosensory Disorders @ Monell Chemical Senses Center
PROJECT SUMMARY Building on the NIDCD Strategic Plan (2017-2022), we propose an interdisciplinary two-day conference to identify high-yield research investment opportunities on smell and taste disorders, with a specific focus on gene therapy and stem cell treatments. Our objectives are to (1) increase collaboration across fields by inviting scientists addressing similar topics in both the chemical senses and other tissues or systems, (2) produce a peer-reviewed, group-consensus recommendation for next steps in research, and (3) communicate conference findings to scientists, clinicians, and patients. Ensuring diversity among attendees is a priority with accommodations offered as needed for people with special needs. The conference will be face-to-face with time for small group discussion. We will also release edited videos of the outreach content.
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2018 — 2019 |
Mainland, Joel D |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Genetic Causes of Congenital Anosmia @ Monell Chemical Senses Center
PROJECT SUMMARY Olfactory disorders such as anosmia have received little attention relative to other sensory deficits. Identifying genetic alterations that lead to blindness and deafness has been critically important for developing gene therapies, in which a faulty gene is replaced with a working one, for both disorders. Over 100 altered genes have been discovered in patients born without hearing and over 200 genes are implicated in patients born without sight. These numbers are in stark contrast to the number of genes implicated in congenital anosmia; to date, researchers have identified only two genes associated with congenital smell loss. Our lack of understanding of congenital anosmia prevents many anosmics from knowing if their condition is acquired or genetic, temporary or permanent, and provides them little hope for diagnosis and treatment. This project will recruit patients with congenital anosmia and use exome sequencing to identify genes underlying this disorder.
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2019 — 2021 |
Dalton, Pamela Helen (co-PI) [⬀] Mainland, Joel D Reed, Danielle Renee (co-PI) [⬀] |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Interdisciplinary Training in the Chemical Senses @ Monell Chemical Senses Center
Project Abstract: The Monell Chemical Senses Center Institutional (T32) Postdoctoral Training Program provides a unique opportunity for postdoctoral fellows to obtain training at the world?s foremost center for research into the chemical senses?taste and smell. Twenty-three faculty members have diverse scientific and international backgrounds and conduct collaborative, multidisciplinary research using specialized methods derived from disciplines such as electrophysiology, molecular biology, genetics, analytical chemistry, and psychophysics. Many applicants to the training program have little background in chemosensation but are given the opportunity to apply skills learned elsewhere to chemical senses research. In addition to specialized hands-on research training provided by faculty mentors, fellows attend instructional courses, workshops, and journal clubs; they have opportunities for small-group review of data, one-on-one assistance with clear scientific communication, and instruction on academic ethics tailored to their stage of professional development. A three-person mentoring committee helps formulate an individual training plan for each fellow?s unique career path and then tracks the fellow?s progress, helps set practical scientific goals, suggests skill development opportunities (e.g., learning new statistical or wet-lab techniques), and provides written feedback every six months. There is emphasis on learning the skills to prepare results for publication and to write successful research grants. During the previous funding period, Monell?s T32 program supported nine postdoctoral fellows; four are still in training, and five now have positions in academic institutions or elsewhere in the biomedical research workforce. All the trainees have published papers in appropriate peer-reviewed journals, attended national and/or international conferences, sought specialized training in courses and workshops, and become familiar with new standards for the responsible conduct of research (including rigor and reproducibility). Four trainees have won awards for excellence in research; others have won competitive research grants, including three Individual Research Training Grants (F32s) and one similar governmental award. The long-term goal of Monell?s Postdoctoral Training Program is to train independent scientists in taste and smell biology, part of NIH?s mission to improve the nation?s health.
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2019 — 2021 |
Mainland, Joel D |
U19Activity Code Description: To support a research program of multiple projects directed toward a specific major objective, basic theme or program goal, requiring a broadly based, multidisciplinary and often long-term approach. A cooperative agreement research program generally involves the organized efforts of large groups, members of which are conducting research projects designed to elucidate the various aspects of a specific objective. Substantial Federal programmatic staff involvement is intended to assist investigators during performance of the research activities, as defined in the terms and conditions of award. The investigators have primary authorities and responsibilities to define research objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations and conclusions of their studies. Each research project is usually under the leadership of an established investigator in an area representing his/her special interest and competencies. Each project supported through this mechanism should contribute to or be directly related to the common theme of the total research effort. The award can provide support for certain basic shared resources, including clinical components, which facilitate the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence. |
Representation of Perceived Odor Intensity @ New York University School of Medicine
Project Summary (Project 3: Representation of perceived odor intensity) The odor of French fries contains more than 500 molecules, but can be replicated by combining only 21 of them. The key to understanding which molecules matter and which are irrelevant is odor intensity. When odors are used to convey information, whether it be the ripeness of a fruit, the note of a predator, or the aroma of a potential mate, intensity is required to know how much is present and where to locate the source. Several neural models have been proposed to explain how the brain represents intensity, but most experimental manipulations manipulate intensity indirectly, by changing odor concentration, rather than directly delivering stimuli at a targeted perceived intensity. In this proposal we use human and mouse behavior to measure the perceived intensity of odors, and then use intensity-balanced odors to probe the neural correlates of perception. With access to the perceptual readout in a model system, we can also use genetic manipulations and optogenetic stimulation to probe how receptor activation profiles translate into perceived intensity. By examining both neural and perceptual responses to the same stimuli across both species, these experiments will reveal how intensity is encoded by receptor activation patterns, the bulb, and the cortex and develop models that predict perceived intensity based on either chemical structure or neural activity patterns.
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2020 — 2021 |
Mainland, Joel D |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Predicting Human Olfactory Perception From Molecular Structure @ Monell Chemical Senses Center
PROJECT SUMMARY Modern technology makes it possible to capture a visual scene as a photograph, alter it, send it to another country nearly instantaneously, and store it without concern for degradation. None of this is currently possible in olfaction. Although perfumers and flavorists are adept at mixing odorous molecules to produce a desired perceptual effect, the rules underlying this process are poorly understood at a quantitative level. Current methods for displaying odors to a subject are akin to requiring a Polaroid of every visual stimulus of interest. A more efficient method for probing the olfactory system would be to use a set of 'primary odors'?some limited number of odors from which all other complex odors could be reproduced by appropriate mixtures. Both auditory and visual stimuli have been digitized, and this will eventually be possible in olfaction as well. Predicting odor from chemical structure has been a problem in the field since its inception, but recent advances in machine learning algorithms have made great progress in analogous problems, such as facial recognition. The research proposed here will combine these machine learning techniques with high quality human psychophysics to understand how to predict the smell of a molecule or mixture of odorants, which will ultimately help improve our understanding of disease diagnosis using odors as well as eating-related health and illness.
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