1998 — 1999 |
Featherstone, David E |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Molecular Dissection of Glutamate Receptors
Glutamate is the primary excitatory neurotransmitter in the mammalian brain. Many important neural functions (including synaptic response duration, learning and memory) are thought to be dependent on specific subunit-conferred glutamate receptor properties. Changes in glutamate receptor function have also been implicated in many abnormal phenomena, such as epilepsy, schizophrenia, Alzheimer's and Huntington's diseases, neurodegenerative diseases, and excitotoxicity secondary to stroke. The broad aim of this proposal is to study how subunit composition determines glutamate receptor function and neural behavior, using the model organism C. elegans. Specifically, this proposed work will: 1) develop electrophysiological methods for reliably recording glutamate responses from identified neurons in C. elegans. 2) Characterize the glutamate response of an identified neuron in both wildtype animals and in mutants in which each glutamate receptor subunit has been deleted, and 3) Characterize behaviors mediated by the identified neuron in both wildtype and mutant animals. This project will build on the trainee's electrophysiology experience and introduce him to molecular biology and genetics while developing a powerful new model system for future work in molecular neurobiology.
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0.976 |
2003 — 2006 |
Featherstone, David E |
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. |
Molecular Basis of Glutamate Receptor Field Formation @ University of Illinois At Chicago
[unreadable] DESCRIPTION (provided by applicant): Excitatory signaling in the central nervous system occurs primarily via glutamate receptors. A molecular understanding of the development, maintenance, and modulation of postsynaptic glutamate receptor fields is therefore very important. However, the molecular mechanisms underlying glutamate receptor field formation are incompletely understood. We are addressing this problem by identifying genes and mechanisms involved in glutamate receptor field formation using a genetic approach in Drosophila. We have isolated several allelic mutations that result in complete and specific loss of postsynaptic glutamate receptor fields. We will identify and clone the mutant gene (which we named 'bad reception', abbreviated 'brec'), then determine the expression and localization of both the brec gene and protein [aim 1]. Properly localized postsynaptic glutamate receptor fields do not form unless the postsynaptic cell is first contacted by the presynaptic cell. After presynaptic contact, glutamate receptor field function increases several hundred-fold within minutes. The molecular mechanisms underlying this process are unknown. To determine whether brec or similar proteins could be involved in this process, we will test whether the initial induction of glutamate receptor fields requires transcription of new receptor subunit genes, or primarily involves translation of pre-existing, possibly pre-localized, receptor subunit mRNAs [aim 2]. To help understand the function of brec and similar proteins in vivo, we will generate and utilize glutamate receptor subunit transgenes tagged with green fluorescent protein (GFP) [aim 3]. Finally, we will continue our forward genetic search for new genes involved in the development of postsynaptic glutamate receptor fields [aim 4] using the new tools and knowledge generated in aims 1-3. The proteins and mechanisms identified in this study (including brec) represent potential drug targets that could be important for understanding and treating neurological conditions such as epilepsy, schizophrenia, damage due to stroke, learning disorders, spinal cord regeneration, or drug addiction [unreadable] [unreadable]
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1 |
2014 — 2017 |
Featherstone, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Functional Characterization of Optimus Prime @ University of Illinois At Chicago
Genome sequencing has provided a "parts list" for all life. The next great challenge is understanding what all those parts do. Toward this end, Dr. Featherstone is leading biology students to systematically search the genome for previously overlooked 'parts', with a specific focus on discovering uncharacterized genes required for brain development. Using this approach, Featherstone?s group discovered a fundamentally new type of protein that they named 'Optimus prime' (OPr). This project will focus on characterizing the function of OPr in order to expand our understanding of normal brain development. Since human OPr has been linked to autism, bipolar disorder, and migraine, the work also has potential to inform our understanding of certain neurological diseases The project will provide training for a diverse group of students, including students from populations underrepresented in scientific disciplines and scientists who would otherwise not have access to leading research facilities.
OPr was discovered using genetic and biochemical screens in Drosophila melanogaster, which for over a century has proven an ideal tool for basic biological discovery. Preliminary studies suggest that OPr associates with specific glutamate receptor subunit mRNAs to control glutamate receptor subunit protein production and synaptic receptor subtype composition ? processes which are universally recognized as important for brain development and plasticity, but which are still very poorly understood. To test this idea, Dr. Featherstone and his team of students will engineer Drosophila completely lacking the OPr gene and then assay glutamate receptor production and function using a variety of powerful techniques. This will determine the functional role of OPr in the developing brain. In a separate line of experiments, Dr. Featherstone and his team will examine the biochemical and spatial relationship between OPr and mRNA, to better understand, at a molecular level, exactly how OPr works.
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0.915 |