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High-probability grants
According to our matching algorithm, Matthew Whim is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2004 — 2005 |
Whim, Matthew |
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.) |
Amperometric Detection of Neuropeptide Release @ Pennsylvania State University-Univ Park
DESCRIPTION (provided by applicant): The long-term goal of this research is to develop a new technique that can monitor the release of identified neuropeptides. These transmitter molecules are found throughout the nervous system and regulate a wide variety of physiological processes. Changes in their patterns of release have been implicated in a spectrum of diseases including epilepsy and hypertension. However to fully appreciate the roles that these transmitters play in the physiological and pathological functioning of the nervous system requires that the factors controlling their release be identified. Due partially to the large number of different neuropeptides it is difficult to monitor the release of specific peptides on a physiological time scale. Amperometry is a technique that fulfills the important requirements of sensitivity and temporal resolution but can't be widely applied since many peptides are not oxidizable. We therefore propose to develop short oxidizable peptide tags that can be inserted into any neuropeptide prohormone. Following translation of the "tagged" prohormone these oxidizable peptides will act as unique molecular markers for a specific population of dense core granules. Secretion of the tag (and thus the other peptides on the same prohormone) can then be measured using amperometry. One advantage of this approach is that potentially it can be applied to any sequenced neuropeptide. To examine the utility of the technique we propose to test it in a variety of cell types and ultimately to develop a transgenic mouse that harbors the oxidizable tag in a restricted population of neuropeptide-containing dense core granules. The reagents that we propose to develop would allow the technique to be used by neuroscientists investigating a wide range of clinically relevant questions.
|
0.942 |
2008 — 2012 |
Whim, Matthew |
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. R56Activity Code Description: To provide limited interim research support based on the merit of a pending R01 application while applicant gathers additional data to revise a new or competing renewal application. This grant will underwrite highly meritorious applications that if given the opportunity to revise their application could meet IC recommended standards and would be missed opportunities if not funded. Interim funded ends when the applicant succeeds in obtaining an R01 or other competing award built on the R56 grant. These awards are not renewable. |
Neuropeptide Y and the Control of Catecholamine Secretion From the Adrenal Gland @ Pennsylvania State University-Univ Park
PROJECT SUMMARY. The inner region of the mammalian adrenal gland is composed of sympathetic neurons that release the catecholamine hormones epinephrine and norepinephrine into the blood. During the fight-or-flight response, these hormones are released from the adrenal gland and prime the organism for the sudden demands that may be placed upon the circulatory, respiratory, musculoskeletal and metabolic control systems. Consistent with their wide-reaching actions, the inappropriate activity of the adrenal gland has been associated with a variety of diseases including hypertension. The long-term objective of the proposed study is to determine the mechanisms that normally control the release of these adrenal hormones. One control pathway is believed to arise from the secretion of transmitters that are co-released with the catecholamines and that mediate [unreadable]short feedback loops[unreadable] within the gland itself. The identity of these co-transmitters and the condition(s) under which they released are not clear. However one strong candidate is neuropeptide Y, a polypeptide that is synthesized by chromaffin cells. Our hypothesis is that neuropeptide Y is an adrenal neurotransmitter whose release mediates short feedback loops that regulate catecholamine secretion. To test this hypothesis we have 3 specific aims that we will address using murine sympathetic neurons (chromaffin cells) and adrenal slices. In the first set of experiments we will test the hypothesis that the net effect of NPY is to increase the secretion of the catecholamines. Our second specific aim is to test the hypothesis that the release of NPY can regulate catecholamine secretion in an autocrine (cell-limited) manner. In the third set of experiments we will test the hypothesis that NPY can also regulate catecholamine secretion by altering the strength of the pre-synaptic input that normally limits catecholamine secretion. By using in vitro and in situ preparations and by employing electrophysiological and molecular techniques we will comprehensively determine whether local feedback pathways control catecholamine secretion. Although this work examines the regulation of the adrenal gland, similar mechanisms are likely to control the release of hormones from many different types of endocrine tissue.
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0.942 |