1971 — 1988 |
Laird, Charles |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Chromosome Structure and Function @ University of Washington |
1 |
1985 — 1994 |
Laird, Charles |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Chromosome Function @ University of Washington |
0.915 |
1986 — 1993 |
Laird, Charles 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. |
Chromosome Structure @ University of Washington
The proposed research is directed at understanding principles of chromosome structure. Three specific questions will initially be asked: (i) What genetic decisions or information are required for formation of polytene chromosomes of Drosophila? (ii) What sequences at Drosophila chromosome region 11A are responsible for the properties of "intercalary heterochromatin" and meiotic recombination? (iii) Does the fragile-X mutation in human chromosomes, and a subsequent chromosome "imprint," lead to late-replicating DNA at Xq27? The health relatedness of this project is as follows: question (i) may lead to methods to induce polyteny in cultured human cells, which would provide useful material for human gene mapping; question (2) may provide insight in meiotic properties of Drosophila chromosomes that are applicable to the human fragile X chromosome; question (iii) is expected to provide direct information about the human fragile X mutation and putative chromosome imprinting event that are responsible for the most common cause of inherited mental retardation in humans. Methodologies involve cytogenetic, genetic, and molecular analysis of chromosomes and DNA. Recombinant DNA technology, DNA sequencing, P-element transformation of Drosophila, and genetic analysis will be used for this research.
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1 |
1995 — 2004 |
Laird, Charles 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. |
Molecular Genetics and Epigenetics of Fragile X Syndrome @ University of Washington
DESCRIPTION: (Adapted from investigator's abstract) This project investigates several aspects of DNA methylation and replication related to fragile X syndrome. The applicant and colleagues have observed that with repeat expansion the FMR1 gene is abnormally methylated (and thereby transcriptionally inactivated) and that its replication is abnormally delayed. The methylation pattern, as determined by protection from bisulfite conversion, showed a remarkable dichotomy: alleles are either highly methylated or not, with few intermediates. The degree of methylation varies, however, with some sites (apparently binding sites for transcription factors) less methylated than others. The methylation pattern is relatively conserved through cell division. DNA replication, as determined by BrdU incorporation in cells by sorted by DNA content and cyclin B1 staining, occurs quite late in the cell cycle, within 90 minutes of mitosis for FMR1 and as much as 1% of total genomic DNA. This observation cells into question the traditional concept of a gap (G2) between DNA replication and chromosome condensation for mitosis, and it may explain sites of chromosome fragility. In the renewal period, the applicants will further pursue the phenomena of DNA methylation and delayed replication. They will characterize the methylation pattern of the FMR1 region in different cell types at different stages of the cell cycle. They will examine clonal conservation of methylation patterns through cell division. They will study late DNA replication in cells sorted with an antibody to phosphorylated histone H3 and in conditions that promote chromosome fragility. Finally they will further develop and use a technique called "boomerang PCR" to determine the direction of DNA synthesis in relation to methylation.
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1 |
1998 — 2005 |
Laird, Charles Hood, Leroy [⬀] Allen, Ethan Wise, Rosalind Sotak, Robert (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Middle School Science Systemic Change Partnership @ University of Washington
9813923 Hood
This five year Local Systemic Change in Science, 6-12, provides a consortium of the Seattle Public Schools, Bellevue, Northshore, Highline, and Shoreline School districts along with the University of Washington and other community partners to infuse inquiry-based teaching of exemplary curricula into all middle schools in the five school districts. All of these districts are contiguous. All middle school science teachers will have at least 165 hours of formal professional development over the five years. Whole science departments from each school will participate together. Inquire-based learning experiences, based around exemplary curricula, will be provided through summer institutes, school-based implementation support during each year, and ongoing partnerships participating teachers. Resource Teachers, and teams of scientists. 350 teachers will be directly involved in the project.
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0.915 |
2006 — 2008 |
Laird, Charles 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. |
Shotgun Hairpin-Bisulfite Pcr Reveals Genome Methylation and Sequence Variation @ University of Washington
[unreadable] DESCRIPTION (provided by applicant): Both DNA methylation and single nucleotide polymorphisms (SNPs) are considered major contributors to human phenotypic variation. We propose a genomic approach that will accurately reveal both epigenetic DNA methylation patterns and genetic information for alleles of individual cells. We have previously obtained both genetic and epigenetic information for promoters of individual alleles for a small number of loci. We have demonstrated that shotgun hairpin-bisulfite PCR is feasible for human LINE-1 (L1) loci and propose to extend this approach to promoter regions containing CpG islands. Our "shotgun hairpin-bisulfite PCR" approach is made possible by combining experimental and analytical methods recently developed in the Pi's laboratory. The methods include (i) hairpin-bisulfite PCR to determine double-strand DNA methylation patterns and SNPs for individual DNA molecules; (ii) shotgun ligation of hairpin linkers to CpG-islands of L1s to capture a broad representation of many L1 loci; (iii) batch-stamping and barcoding of individual genomic DNA fragments to authenticate each sequenced molecule; (iv) population-epigenetic modeling to analyze site-specific methylation patterns quantitatively and statistically. Funds are requested to screen about 5000 gene promoters in normal human leukocytes, covering approximately 15-30% of human CpG islands. Our innovative strategy will initiate a more systematic characterization of combined epigenetic and genetic variations in normal and diseased cells. [unreadable] [unreadable] [unreadable]
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1 |
2008 — 2009 |
Laird, Charles D |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Administrative Core @ University of Washington
The overall objective of the Administrative Core is to provide an organizational structure to support and foster a creative, state-of-the-art interdisciplinary research program of biomedical, behavioral, and biobehavioral research relevant to the field of developmental disabilities. This is accomplished through scientiflc and programmafic leadership, through administrative and management support to scientific Core facilities and research projects, and by providing mechanisms for communication and dissemination.
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1 |
2008 — 2009 |
Laird, Charles D |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Origins of Variarion in Abnormal Fmr1 Methylation in Fragile X Syndrome @ University of Washington
Developmental Disabilities; FMR1; Fragile X Syndrome; Methylation; Research
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1 |