| NSF Org: |
MCB Division of Molecular and Cellular Biosciences |
| Recipient: |
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| Initial Amendment Date: | January 18, 2002 |
| Latest Amendment Date: | January 18, 2002 |
| Award Number: | 0131604 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Rita Teutonico
MCB Division of Molecular and Cellular Biosciences BIO Directorate for Biological Sciences |
| Start Date: | February 1, 2002 |
| End Date: | June 30, 2005 (Estimated) |
| Total Intended Award Amount: | $357,005.00 |
| Total Awarded Amount to Date: | $357,005.00 |
| Funds Obligated to Date: |
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| History of Investigator: |
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| Recipient Sponsored Research Office: |
921 S 8TH AVE POCATELLO ID US 83201-5377 (208)282-2592 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
921 S 8TH AVE POCATELLO ID US 83201-5377 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): |
Genetic Mechanisms, EPSCoR Co-Funding |
| Primary Program Source: |
04000203DB NSF Education & Human Resource |
| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.074 |
ABSTRACT
The genomes of multicellular eukaryotes exist in two distinct chromatin states, the loosely compacted euchromatin and the generally condensed heterochromatin. Scientific studies using the fruit fly, Drosophila melanogaster, first revealed that this structural subdivision correlated with differences in gene activity over 60 years ago. There is growing appreciation for the importance of chromatin structure in gene expression, but our understanding of chromosome structural differences at the protein level and how this impacts gene expression is still in its infancy. One focus of this research project is the analysis of two Drosophila genes genetically identified as important for antagonizing heterochromatin formation and promoting a euchromatic chromatin state, E(var)3-5 and E(var)3-9. The specific objectives are to extend phenotypic characterization of E(var)3-5 and E(var)3-9 mutants and to map, clone and molecularly analyze each gene. Previous experiments showing that E(var)3-5 and E(var)3-9 mutations affect gene expression will be extended and include multiple alleles. The embryonic lethality associated with mutations in both genes will be investigated to determine the timing and characteristics of developmental arrest, potentially yielding insight into the normal activity of each gene product. Evidence for a role in mitotic or meiotic chromosome function will be investigated through assays for chromosome loss, and altered behavior and morphology. The E(var)3-5 and E(var)3-9 genes will be mapped and then cloned, followed by DNA sequence analysis to predict features of the protein products. The expression pattern of each gene will be examined. The second research focus is the functional analysis of the D1 gene, which encodes an abundant protein that binds to satellite DNA within heterochromatin. Mutant alleles of the D1 gene will be generated and characterized, as a means to elucidate the function of the D1 protein. D1 mutants will be studied to determine if the D1 gene is essential for viability, and if so, to characterize the timing and phenotypes associated with developmental arrest. Through experiments analogous to those performed to analyze the E(var) mutants, flies bearing mutant D1 alleles will be examined to reveal a potential role for D1 in mitotic and interphase chromosome structure, chromosome dynamics and gene expression. It is anticipated that the molecular and genetic characterization of these three genes will increase our understanding of protein determinants of chromosome structure and their role in normal chromosome function.
The aim of this research is to increase the understanding of chromosome structure by the genetic analysis of several structural components and regulators, using the fruit fly as a model system. Two genes genetically identified as being important for chromosome structure will be cloned and analyzed to better define their roles. The function of an abundant chromosomal protein will be elucidated through the isolation and characterization of mutant alleles of its gene. The findings of these studies should be applicable to other organisms and contribute to our general understanding of the importance of chromosome structure for cell function.
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