1974 — 1978 |
Nelson, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Development of a Program in Chemical Technology |
0.907 |
1975 — 1977 |
Nelson, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Instructional Scientific Equipment Program |
0.951 |
1977 — 1979 |
Nelson, David [⬀] Nelson, David [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Role of Lipids and Proteins in Membrane Excitation in Paramecium @ University of Wisconsin-Madison |
0.913 |
1978 — 1981 |
Nelson, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Introduction to Polymer, Solid State, and Electroorganic Synthesis |
0.907 |
1981 — 1986 |
Nelson, David [⬀] Nelson, David [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
The Role of Lipids in Membrane Excitation in Paramecium @ University of Wisconsin-Madison |
0.913 |
1992 — 2002 |
Nelson, David Loren |
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 Analysis of Fragile X Syndrome @ Baylor College of Medicine
DESCRIPTION: (adapted from the Investigator's abstract). Fragile X syndrome is among the most common human single gene disorders and the leading cause of inherited mental retardation. The most common mutation reduces expression of the FMR1 gene through expansion and methylation of an unstable CGG trinucleotide repeat. Two similar repeats are found nearby on the X chromosome which can expand and become unstable. All three sequences lead to cytogenetically visible fragile sites in their largest forms. Two sites, FRAXA and FRAXE lead to mental retardation associated with the FMR1 and FMR2 genes, respectively. The third, FRAXF, appears to be benign. This project seeks to continue study of these two genes leading to mental retardation. It will continue analysis of functional aspects of FMR1 and proposes to extend these studies to FMR2. It plans to study the roles of FMR1-related genes FXR1 and FXR2. These genes are similar in sequence to the FMR1 gene, and appear to interact with the FMR1 gene product in vivo. All three genes have properties of RNA binding proteins and may be involved in regulating RNA metabolism. The RNA targets of these three proteins may be important to the finding of mental retardation. FMR2 is unrelated in sequence and has features reminiscent of a transcription factor; however, it is highly expressed in portions of the brain associated with learning and memory, explaining the mental retardation seen in individuals lacking the protein. Specific aims are: 1) identification and characterization of mRNAs mis-regulated by absence of or lesions in FMR1 and FXR2; 2) development of mouse models to delineate developmental and temporal requirements for FMR1 in learning and behavior, and to study structure/ function aspects of FMR1.; 3) continued characterization of FMR1 and interacting proteins through two hybrid and mutation screens, 4) targeted disruption of the murine Fxr2 locus and description of the phenotype. If viable homozygotes can be produced, this animal will be crossed with the Fmr1 knockout mouse to determine the effect of the double knockout; 5) characterization of the FMR2 gene defective in FRAXE mental retardation.
|
0.958 |
1993 — 1997 |
Nelson, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Development of New Synthetic Methodology For the Organic Laboratory
9351620 Nelson This project will address a new approach to instruction in the large-enrollment service undergraduate Organic Chemistry Laboratory, characterized by new synthetic methodology based on the use of supported reagents and catalysts that could be used in the undergraduate organic laboratory, and more extensive use of GC and (FT)IR instrumentation commonly found in undergraduate organic labs. In the case of supported materials, syntheses would be carried out on or catalyzed by material adsorbed or bound ionically or covalently to various supports. The supports would be similar to silica-based or styrene-divinylbenzene HPLC bonded phases, and be used in set-ups commonly referred to as solid phase extraction (SPE) devices. There is a wide variety of these materials commercially available at this time. Equivalent materials can be prepared by the user if desired at a considerable cost saving. A second group of experiments would be designed as catalytic vapor phase reactions that could be carried out in a modified injection port of a gas chromatograph. An alternative set-up would involve a small reactor column placed either in the column oven of the G.C. or in an auxiliary oven and used in conjunction with multiport valves. The gas chromatograph would then be used to analyze, and possibly isolate, the reaction products. Experiments would emphasize principles rather than product isolation and characterization.
|
0.907 |
1994 |
Nelson, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
A Tunable Laser Based Monitor For Hocl and Hcl in the Marinetroposphere
9360606 Nelson The possibility that atomic chlorine concentrations in the marine surface layer are large enough to compete with the hydroxyl radical as the major tropospheric oxidizer has received considerable speculation. Chlorine atoms participate in the oxidation of hydrocarbons and dimethyl sulfide and can also directly influence tropospheric ozone loss through catalytic cycles with chlorine monoxide and the hydroperoxy radicals. The net effect on the ozone budget may be highly dependent on the partitioning of the inorganic chlorine pool between hydrochloric acid, hypochlorous acid, chlorine gas, and chlorine nitrate. In order to assess the potential importance of chlorine chemistry, direct measurements of these species are necessary. In Phase I of this research, the PIs will assess the feasibility of detecting hypochlorous acid at the 10 to 20 ppt level using tunable diode laser infrared absorption. This will require (1) measurement of pressure broadening coefficients for selected absorption lines, (2) identification of suitable spectral regions, (3) investigation of photolytic modulation of hypocholorous acid to implement background subtraction, and (4) design of novel multiple pass absorption cell with a path length of at least 600 meters. Phase II research will improve the basic spectroscopic parameters for quantifying hypochlorous acid concentrations and develop a prototype field instrument capable of simultaneous measurements of hydrochloric acid and hypochlorous acid in the marine atmosphere. ***
|
0.901 |
1994 — 1996 |
Nelson, David Loren |
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. |
Bcm Human Genome Program @ Baylor College of Medicine |
0.958 |
1996 |
Nelson, David Loren |
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. |
New Analysis Tools For Gene Function Identification @ Baylor College of Medicine |
0.958 |
1996 |
Nelson, David Loren |
R13Activity Code Description: To support recipient sponsored and directed international, national or regional meetings, conferences and workshops. |
X Chromosome Sequencing Workshop @ Baylor College of Medicine |
0.958 |
1996 — 1998 |
Nelson, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Sbir Phase Ii: a Tunable Laser Based Monitor For Hoc1 and Mc1 in the Marine Troposphere
9423289 Nelson The possibility that atomic chlorine concentrations in the marine surface layer are large enough to compete with hydroxyl radical (OH) as the major tropospheric oxidizer continues to receive considerable speculation. Chlorine atoms participate in the oxidation of hydrocarbons, dimethyl sulfide, and can also directly influence tropospheric ozone loss through catalytic cycles with chlorine monoxide (ClO) and hydroperoxy (HO2) radicals. The net effect on the ozone budget may be highly dependent on the partitioning of the inorganic chlorine pool between four chlorine-containing gases; hydrogen chloride (HCl), hypochlorous acid (HOCl), molecular chlorine (Cl2), and chlorine nitrate (ClONO2). To assess the potential importance of chlorine chemistry in the lower atmosphere, direct measurements of these species are necessary. In Phase I of this research, the feasibility of detecting both HCl and HOCl down to the 10 to 20 part-per-trillion (pptv) concentration range by tunable diode infrared laser absorption was demonstrated. The Phase II research effort will improve the basic spectroscopic parameters for quantifying HOCl concentrations in the atmosphere, and develop and construct a prototype field instrument capable of simultaneous measurements of HCl and HOCl in the marine troposphere. This new instrument will be laboratory tested and evaluated against existing, albeit nonselective, inorganic chlorine techniques in an intercomparison. The instrumentation produced as a result of this research program will be useful for measuring other trace gases in addition to HCl and HOCl. The novel long path, multiple pass absorption cell developed during this project will have independent commercialization potential for other laser absorption systems used to monitor industrial pollutants, toxic wastes, and various gases emitted from combustion processes.
|
0.901 |
1997 — 2005 |
Nelson, David Loren |
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. |
Sequence and Haplotypes For Analysis of Cancer Genes @ Baylor College of Medicine
DESCRIPTION (Applicant's Abstract): This application requests renewed funding for a project to develop reagents for testing specific genes for association with cancer predisposition. In the initially funded application, efforts were focused on development of genomic sequence data from numerous genes with known or suspected involvement in cancer predisposition, and on the development of reagents capable of detecting variation at these loci in pilot studies. The initial request was for three years of funding. The rationale for the short time frame was in part due to the rapid changes in human genome sequencing program (HGP), such that the utility of the proposed sequencing efforts might be diminished by the rapid advancement of the HGP. Moreover, the ability to develop and characterize SNPs at the loci of interest, and their potential utility in defining haplotypes were both unknown. In this request for renewed funding, the role of genomic sequencing has been reduced to "finishing" clones in order to provide high quality, contiguous sequence for genes with suspected cancer involvement. Improved methods for the identification and typing of SNPs are proposed in order to accelerate these efforts. Finally, subcontracts with experts in population and statistical genetics are included that will provide improved approaches to the design and execution of association studies based on complex haplotypes. This addition to the project is essential for the final aim of pilot association studies. The project is composed of the following aims: 1. Sequencing of the target genes initiated in the project will be completed. 2. Identification of SNPs will continue, through the use of publicly accessible database entries, and by direct identification, resulting in genetic reagents available for association studies for 25 additional genes. 3. Methods will be developed to improve detection and typing of SNPs in the targeted loci. 4. Methods for improved haplotype inferences from multiple SNP site genotype data will be developed. 5. Methods will be developed to utilize haplotypes associated with phenotype to locate and identify possible site of variation responsible for the phenotype. 6. Pilot association studies with the markers and haplotypes developed will be initiated.
|
0.958 |
1997 — 2000 |
Nelson, David Loren |
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 Analysis of Xg28-Linked Incontinentia Pigmenti @ Baylor College of Medicine
Incontinentia Pigmenti Type 2 (IP2) is a neurocutaneous genodermatosis showing X-linked dominant inheritance with prenatal male lethality. Affected females are diagnosed at or soon after birth by the presence of a progressive skin rash which is present in streaks or patches following lines of Blaschko. The rash is initially vesicular with marked eosinophilia, and becomes sequentially verrucous, hyperpigmented, and finally hypopigmented. Other findings include dental abnormalities, nail dystrophy, breast hypoplasia, patchy alopecia, and vascular abnormalities of the retina. The retinal abnormalities are the most significant complication of IP2, since they can lead to secondary retinal detachment, micropthalmia, and congenital cataracts. The disease has been mapped to distal X28. This application seeks to identify the gene for IP2, to determine its sequence and genomic organization, to characterize mutations in IP2 patients, and to define the function of the IP2 gene product. The IP2 critical region will be refined by characterization of additional recombination events. Yeast artificial chromosomes spanning the critical region will be used to identify cosmids, which will be assembled into contigs. These cosmids will be used to scan for genomic rearrangements in IP2 patients by Southern hybridization and by fluorescence in situ hybridization. Cell lines carrying the IP2 mutation on the active X chromosome will be isolated and used to identify differentially expressed mRNas. Any which map to the IP2 critical region will be pursued as candidates. Human homologs of the mouse xlr3 genes, which lie within the critical region for Striated, a mouse mutation which may represent the mouse homolog of IP2, will be identified and tested as candidates. Genomic sequence data will be analyzed as it becomes available. ESTs which are mapped by sequence identify, as well as putative exons identified by computer algorithms such as GRAIL, will be used to clone full-length cDNAs. These will then be tested as candidates. When the gene is identified, its complete sequence and genomic organization will be determined. The mutation present in each IP2 family will be determined, and will be related to phenotype and presence or absence of skewed X inactivation. The expression pattern of the gene will be studied by RNA in situ hybridization to mouse embryo sections. The subcellular localization of the IP2 protein product will be determined using monoclonal antibodies, and cell lines carrying IP2 mutations will be compared with normal cell lines. Other proteins which interact with the IP2 protein will be identified using the yeast two-hybrid system.
|
0.958 |
1999 |
Nelson, David Loren |
R24Activity Code Description: Undocumented code - click on the grant title for more information. |
Baylor College of Medicine Microarry Facility @ Baylor College of Medicine
As recently as two years ago there were few microarray technologies available. In the last year, in both industrial and academic settings, new methodologies for fabricating microarrays and novel detection systems have been developed. The technologies that are currently available through commercial ventures are very expensive. The actual cost of these technologies is beyond the reach of small university-based research laboratory budgets. Furthermore, the needs of the university-based researchers are usually quite specific and dictate the need for custom arrays that are not commercially available. The challenge that faces this group of NCI-funded researchers is how to take advantage of these technologies within the constraints of R01 budgets. Our goal is to be able to build microarrays that are of high density enabling us to simultaneously measure the expression of a major portion of the genome at one time. The Program Announcement sponsored by the NCI entitled "Shared Resources for Scientists Outside NCI Cancer Centers" affords us the opportunity to address array fabrication and enhance array detection to be more flexible. Our goal is to build a shared resource core dedicated to making and using DNA microarrays for a better understanding of the genes involved in tumorigenesis. In particular, we would like this core to have the ability to make custom arrays, a capacity that is imperative to remain competitive. With the custom "in-house" facility, we can pursue microarray assays not commercially available and at a much lower cost. Microarrays of this sort make sense for many applications within our laboratories including gene expression, genotyping, re-sequencing and mutation screening assays.
|
0.958 |
1999 — 2003 |
Nelson, David Loren |
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. |
Fragile X Related Genes in Mental Retardation @ Baylor College of Medicine
Fragile X syndrome (MIM number 30955) is among the most common human single gene disorders, and is the leading cause of inherited mental retardation, with an estimated frequency of 1/2000-1/4000 individuals world-wide. The gene defective in fragile X syndrome (FMR1) was identified by positional cloning in 1991, yet its function, and the consequences of its absence remain unknown. The FMR1 protein interacts with mRNAs in a variety of cell types, and has been shown to associate with ribosomes. These apparently fundamental properties are difficult to reconcile with the relatively mild phenotype found in fragile X patients and in a mouse knockout of the Fmr1 gene. The central hypothesis of the project proposed here is that two FMR1-related proteins, FXR1 and FXR2 provide redundancy of function for FMR1. This redundancy masks the phenotypic consequences of loss of function mutations in humans and mice that would allow better definition of the function of FMR1. In order to test this hypothesis, mutations in the Fxr1 and Fxr2 genes are proposed. These will be introduced into the mouse genome with the capability to provide conditional knockouts using the site specific recombinase Cre derived from phage P1, which recognizes lox P sites for recombination. Mutant mice will be analyzed by biochemical, histological and behavioral methods in order to determine the consequences of the absence of one or more of these genes. Conditional mutations will be created to investigate tissue specific or developmental timing effects of gene ablation. Mutations in the Fxr1 and Fxr2 proteins, especially in combination with Fmr1 mutations, should provide resolution of the redundancy question. Such mutations and combinations of mutations will also provide important evidence for the functions of these genes. Results from this project will provide additional data regarding the normal function of FMR1 and the consequences of its absence in fragile X syndrome. These data will allow further investigation of potential therapeutic intervention in this common form of mental retardation.
|
0.958 |
2000 — 2006 |
Beard, John (co-PI) [⬀] Nelson, David Charlesworth, Debra |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Senior Engineering Design Projects to Assist Disabled Persons in Michigan's Copper Country @ Michigan Technological University
0079969 Wright This is a five-year effort that engages engineering students at Michigan Technological University in the design and development of assistive and/or rehabilitative devices for persons with disabilities. The objective is the completion of four design projects annually, which will assist individual disabled persons served by the Copper Country Intermediate School District (CCISD). Each design project will be assigned to a team consisting of three to five senior students in biomedical engineering, mechanical engineering, and electrical engineering. Students in other disciplines may participate, depending on skills required for a given project. Local high school students will be engaged in fabrication of some of the projects, through a partnership with Hancock (MI) High School's industrial arts program. Each project will be advised by a faculty member -- either one of investigators, or another member of the engineering faculty who has appropriate expertise and interest.
All students who participate in one of these projects will complete a workshop on professional ethics and standards, prior to beginning a project. This workshop will inform the students of applicable standards and issues in patient confidentiality, liability, and intellectual property rights. This workshop will be conducted jointly by members of the professional staff of CCISD and the investigators.
The principal investigator will, by July I of each year, provide the National Science Foundation with a report describing the projects completed.
|
0.901 |
2000 — 2003 |
Nelson, David Loren |
R24Activity Code Description: Undocumented code - click on the grant title for more information. |
Baylor College of Medicine Microarry Facility For Nci Fu @ Baylor College of Medicine
As recently as two years ago there were few microarray technologies available. In the last year, in both industrial and academic settings, new methodologies for fabricating microarrays and novel detection systems have been developed. The technologies that are currently available through commercial ventures are very expensive. The actual cost of these technologies is beyond the reach of small university-based research laboratory budgets. Furthermore, the needs of the university-based researchers are usually quite specific and dictate the need for custom arrays that are not commercially available. The challenge that faces this group of NCI-funded researchers is how to take advantage of these technologies within the constraints of R01 budgets. Our goal is to be able to build microarrays that are of high density enabling us to simultaneously measure the expression of a major portion of the genome at one time. The Program Announcement sponsored by the NCI entitled "Shared Resources for Scientists Outside NCI Cancer Centers" affords us the opportunity to address array fabrication and enhance array detection to be more flexible. Our goal is to build a shared resource core dedicated to making and using DNA microarrays for a better understanding of the genes involved in tumorigenesis. In particular, we would like this core to have the ability to make custom arrays, a capacity that is imperative to remain competitive. With the custom "in-house" facility, we can pursue microarray assays not commercially available and at a much lower cost. Microarrays of this sort make sense for many applications within our laboratories including gene expression, genotyping, re-sequencing and mutation screening assays.
|
0.958 |
2002 — 2006 |
Nelson, David Smith, David (co-PI) [⬀] Bradley, Terence |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Acquisition of Instrumentation For a Genomics Facility in Support of the Uri Environmental Biotechnology Initiative @ University of Rhode Island
A grant has been awarded to the University of Rhode Island to acquire an automated DNA sequencer and supporting equipment. The Environmental Biotechnology Initiative (EBI) at the University of Rhode Island was developed to promote biotechnology at the institution through research, teaching, and outreach. Four central facilities are envisioned for the EBI - Imaging, Genomics and Proteomics, Transgenics, and Bioinformatics. This grant award will establish the URI Genomics Facility by providing funds for the acquisition of a DNA sequencer and ancillary equipment dedicated for sample preparation. Additionally, funds to support the hire of a Research Associate to manage and operate the facility are provided by this award and matching funds from the University of Rhode Island.
The instrumentation and Research Associate will support the currently funded research activities of the three Principal Investigators (PIs) and eight other major users in five separate departments in three different colleges at the university. The funded research projects of the PIs include: studies of gene regulation in the causative agent of Lyme disease (Borrelia burgdorferi), studies of gene regulation in Vibrio anguillarum (a major bacterial pathogen of farmed salmon and other fish), determination of the bacterial species succession of Narragansett Bay, identification of the microbes that inhabit the deep ocean biosphere, determination of the regulation of the molecular mechanisms of osmoregulation in fish, identification of the microbes that inhabit the gastrointestinal tract of salmon, and population genetics of selected marine finfish (e.g., haddock and tautog). The establishment of the Genomics Facility will allow user directed DNA sequencing with more rapid turnaround and lower costs then is presently available to URI-based investigators, who are forced to contract with other academic or commercial sequencing facilities. It also is anticipated that numerous other investigators at URI will make use of the facility.
The ability to study life at the DNA level has fundamentally changed almost every aspect of research in the life sciences. The high sample throughput afforded by automated DNA sequencers allows researchers to address questions concerning genetic diversity and gene regulation that were unapproachable only a few years ago. The Genomics Facility also will play an integral role in training our students in state-of-the-art research methodologies and the art of scientific investigation. The Research Associate will work with interested faculty to develop and refine laboratory exercises in molecular biology that include the theory and practice of the DNA sequencer purchased with these funds. Additionally, it is anticipated that the acquisition of Genomics Facility will enhance the ability to attract new graduate students. URI has actively engaged in the recruitment of students from under-represented groups for some years to enhance the number and quality of such students in our graduate programs in the biological sciences. The availability of this core facility to support the research training of all students is expected to enhance recruitment and retention of students from under-represented groups. The combination of improved research infrastructure and training opportunities will enable URI faculty to better compete for research funds, new faculty, and students.
|
0.907 |
2002 |
Nelson, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Sbir Phase I: Development of a High Precision, Autonomous Quantum Cascade Laser-Based Detector For Methane and Nitrous Oxide
This Small Business Innovative Research (SBIR) Phase I project is to develop a compact and autonomous, high precision monitor for the potent greenhouse gases, methane and nitrous oxide. This proposal is submitted under the Geoscience Instrumentation subtopic (subtopic E) of the Electronics topic. The target molecules are currently detected with cw lead salt diode lasers. These lasers require cryogenic cooling and, due to their lack of long term stability, a highly trained operator. Quantum cascade (QC) lasers are spectroscopically stable and can be operated near room temperature when they are pulsed. This allows the design of compact, rugged, inexpensive and autonomous molecular monitors. This system is further simplified by detecting both methane and nitrous with a single QC laser using nearly coincident transitions near 1300 mm . The Phase I research objectives will be to demonstrate that the required sensitivity and specificity can be obtained in this spectral region using a pulsed QC laser and non-cryogenic infrared detectors. The Phase I research will produce a preliminary design for an instrument to be constructed during Phase II. The resulting turn-key monitor will address the widespread need to monitor these important species in a sensitive and cost-effective manner.
Potential commercial applications for this research include 1) the research market attempting to quantify the worldwide sources and sinks of greenhouse gases, 2) the market for trading credits for greenhouse gas emission reductions which requires quantitative documentation of these reductions, 3) the market for goods and services able to identify and locate leaks in natural gas distribution systems and 4) various research markets needing to quantify methane and/or nitrous oxide concentrations or emissions in both laboratory and field settings.
|
0.901 |
2003 |
Nelson, David |
G08Activity Code Description: A grant available to health-related institutions to improve the organization and management of health related information using computers and networks. |
Internet Connection For Providence Family Physicians @ Providence Medical Group, Inc.
DESCRIPTION (provided by applicant): The overarching goal of this project is to improve the quality of health care services delivered to the residents of rural Citronelle, Alabama. Specific aims are as follows: 1. Purchase and install hardware and software that will support high-speed Internet service and network connectivity between Providence Family Physicians - Citronelle (19140 South 3rd Street, Citronelle, AL 36522) and Providence Hospital's Data Center (6701 Airport Boulevard, Mobile, AL 36608) within two months of grant award 2.Train the physician and the four staff members in use of the high-speed Internet service within two weeks of completed installation and provide technical support services as needed throughout the project period. Providence Family Physicians, a network of 11 family practice centers, is a division of Seton Medical Management, a nonprofit organization. Seton Medical Management and its parent organization, Providence Hospital, nonprofit subsidiaries of Ascension Health. Established in 1854 by the Daughters of Charity, Providence Hospital, a member of Ascension Health, has grown from a 60-bed, center-city infirmary to a 349-bed full service hospital serving southwest Alabama and southeast Mississippi. Its mission is to remain true to its reputation as a values-driven health system that services the health needs of the total individual - body, mind, and spirit. This project will further Providence Hospital's longstanding tradition of ensuring access to high-quality health care to all individuals.
|
0.916 |
2003 — 2006 |
Nelson, David Lipschultz, Fredric Bates, Nicholas Lomas, Michael Knap, Anthony |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Enhanced New Production During Winter Mixing: a Missing Component of Current Estimates @ Bermuda Institute of Ocean Sciences (Bios), Inc.
ABSTRACT
OCE-0241662
Photosynthetic uptake of CO2 by oceanic phytoplankton and the export of the resulting organic carbon to the deep sea comprise a biological pump (Volk and Hoffert, 1985), capable of extracting globally significant amounts of CO2 from the atmosphere. As a consequence, it is important from the perspective of the global carbon cycle to understand both the present efficiency and the main controlling mechanisms of this important carbon pathway. In the open ocean the biological pump is driven by new production of organic matter (production supported by externally supplied nutrients) and export of that organic matter to depth. Many methods have been employed to estimate new production, with varying degrees of agreement. In the Sargasso Sea, for example, geochemical estimates of new production largely exclude the winter mixing period (because their fundamental assumption are valid only during stratified periods). Biological methods suggest that the pre-stratification period can be as important, in terms of new production, as the remainder of the year. Those biological estimates are poorly constrained and based on sparse data. Because of the enormous spatial extent of subtropical gyres similar to the Sargasso Sea, uncertainty in the rate of new production and organic matter export in those systems leads to large uncertainty in biologically-driven carbon fluxes at the global-scale. Recent data suggest that in the Sargasso Sea, the passage of weather fronts leads to increased new production during the winter mixing period. Some oceanographers believe that these events lead to enhanced nitrate input, followed by a rapid biological response and accumulation of biomass, and an equally rapid export of that biomass to depth.
In this project, researchers at the Bermuda Biological Station for Research carry out a process-oriented study of new production and its control during the period before formation of the seasonal thermocline in the BATS/BTM/OFP region near Bermuda. Researchers from Oregon State University, Woods Hole Oceanographic Institution, and the University of South Carolina will also participate in some aspects of the study. This sea-going effort will be conducted during two 30-day cruises (one in 2004 and one in 2005) during the winter mixing period when the passage of these fronts is most common and when few data are available to constrain new production estimates. It will be crucial for this study to sample from a fully weather-capable research vessel, which can stay out and continue operations through most winter storms. The team will use direct measurements of nitrate entrainment, nitrate uptake, phytoplankton community structure change, and dissolved and particulate organic matter export to elucidate the linkages between new production and export production as well as determine the main biological responses to short-term physical forcing. Particular emphasis will be placed on biogeochemically critical phytoplankton groups such as diatoms and coccolithophorids, which can exploit transiently favorable conditions of the kind hypothesized to occur in late winter/early spring and which play a disproportionately large role in organic-matter export in many systems.
An understanding of ocean function is no longer important just to practicing ocean scientists. This project will provide information critical for biogeochemical modelers seeking to constrain future predictions of changes in the oceanic biological pump, and will also provide information of interest to students, teachers and the general public. If in fact a significant, and previously unmeasured, amount of new production occurs in subtropical gyres during the winter mixing period, then biological processes in the central ocean gyres play a greater role in the global carbon cycle including regulation of atmospheric carbon dioxide than we recognize at present.
|
0.915 |
2003 — 2006 |
Nelson, David Shambaugh, Robert [⬀] Papavassiliou, Dimitrios (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Melt Blowing: Advanced Modeling and Experimental Verification @ University of Oklahoma Norman Campus
The goal of this project is to describe with an experimentally verified model the commercially important process of fiber melt blowing. Worldwide, about 150 10kg year of melt blown fabric is produced. Typical examples of this material are Pall Corporation's cartridge filters, Kimberly-Clark's Spunguard surgical gowns, and Du Pont's Tyvek. Tyvek is used for computer diskette sleeves, house wrap, sterile packaging, high strength envelopes, and many other uses. Melt blowing involves the impact of high velocity air streams upon a molten polymer to form fine webs of fiber. We propose to combine computational fluid mechanics CFD to describe the airside flow with a previously developed model by our group for the polymer side. The result should be an accurate, comprehensive model for melts blowing. This comprehensive model will be compared with experimentally determined fiber parameters. The experimental work will primarily be done with the spinning equipment available at the University of Oklahoma. In addition, pilot scale spinning will also be done at the 3M Research Center in St. Paul, MN.
This project will expand the university/industry interface by using the 3M companies as an active collaborator with the university. A 3M research manager will serve as a co-advisor to the students involved in this project. Frequent visits will occur between the personnel at the university and 3M. The 3M companies will donate use of its pilot equipment and analytical facilities. The knowledge gained from this proposal will allow more economical production of nonwoven products that are used in a high-volume, rapidly expanding, billion-dollar market. In addition, the knowledge will help create entirely new processes and products
|
0.909 |
2004 — 2008 |
Nelson, David Loren |
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 Analysis of Xq28-Linked Incontinentia Pigmenti @ Baylor College of Medicine
DESCRIPTION (provided by applicant): Incontinentia pigmenti (IP) is an X-linked dominant and male-lethal disorder that mainly affects the skin, teeth, eyes, and central nervous system. Females survive because of selective proliferation of cells expressing the normal X chromosome and therefore, skewing of X-inactivation in females is a hallmark feature of IP. We recently identified the gene involved in IP and demonstrated mutations in multiple IP patients. The gene, NEMO, is involved in the NF-kB signal transduction pathway and its absence renders cells susceptible to apoptosis. Hence, loss-of-function mutations in males result in embryonic lethality in humans as well as mice. While knockout models of Nemo demonstrate a classic IP phenotype in female mice, the males die during embryonic development. Female IP patients demonstrate a phenotype presumably because of the X-inactivation pattern and the timing of apoptosis in cells expressing the mutant X chromosome. A majority of IP patients carry a deletion of exons 4-10 that occurs due to misalignment, possibly during recombination, of repeats located in intron 3 and at the end of the gene. The remaining patients have demonstrated microdeletions, duplications, and substitutions. Nearly all of our patients exhibit loss-of-function mutations. Although IP has been considered a classic male-lethal disorder, we recently identified mutations in males also, which appear to be hypomorphic and not lethal to the cellular environment. When males have IP, they present other signs not typically associated with IP. Therefore, numerous male IP cases may have been mistaken for another similar disorder due to previous misconceptions about male lethality in classic IP and the presence of atypical signs in surviving IP males. Hence, one of the goals of this project is to examine patients with similar disorders to see if they are allelic with IP. Variant phenotypes due to hypomorphic mutations are likely to reveal significant information about the functioning of NEMO and the NF-kB pathway. In this respect, we have proposed the creation of transgenic mice expressing nonlethal, hypomorphic mutations to investigate the various functions of the NF-kB pathway and the pathogenesis of IP. These transgenic mice will help address the hypothesis that hypomorphic mutations lead to an unstable protein with residual activity and that the specific timing of expression of the mutation leads to the phenotypes observed in humans. As a third goal, this project focuses on understanding NEMO expression by analyzing its product. This effort is expected to provide insight into the control of NEMO expression and its consequence on downstream activity via the NF-kB pathway. Lastly, mutation detection in IP patients is complicated by the presence of a second copy of NEMO located ~75kb distal to the first copy. These two copies share nearly 100% homology between exon 3 and ~10kb distal to exon 10. The second copy (NEMO) lacks exons 1 and 2 and may not be functional. The fourth goal of this project is, therefore, to determine role of this repeated copy in IP mutation. Collectively, the aims of this project will help understand the pathogenesis of IP in males, the regulation of the NF-kB signaling pathway, the regulation of NEMO expression, and the nature of the two NEMO copies.
|
0.958 |
2004 — 2009 |
Bulleit, William (co-PI) [⬀] Nelson, David Archer, Glen (co-PI) [⬀] Zekavat, Seyed [⬀] Hungwe, Kedmon |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Optimizing the Interdisciplinary Course: Introduction to Electrical Engineering (Ee) For Non-Ee Majors @ Michigan Technological University
The intellectual merit of this project is its novel approach to optimize an essential interdisciplinary course. It will create a prototype curriculum available to electrical engineering departments that are charged with providing an introduction to electrical engineering for non-EE majors. The new curriculum will: (1) be attractive, motivational, and relevant to students; (2) provide the optimal level of both range and depth of coverage of EE topics in a curriculum package, and (3) be inexpensive to implement and cost effective for both universities and students. And, although this is not a primary focus of the project, the strategies used, the methodology of developing the new curriculum, and the testing methods may help professionals in other fields who want to examine the relevancy of their coursework.
The broader impacts of this project include development and dissemination of a curriculum package and model that should be useful to all engineering education programs nationally. With an EE background relevant to their particular disciplines, students will be able to work more cooperatively with engineers from other disciplines. This project opens the door to change the way engineering is taught to non-EE engineering majors. The process and the resulting model can serve as a catalyst that prompts engineering educators to find the best ways to teach EE concepts to multidiscipline non-EE engineering students.
The outcome of this project will be the full development and design of a novel and innovative EE curriculum package that includes a course textbook, the laboratory coursework, and the course web-based teaching modules for most non-EE engineering fields. Both fundamental engineering knowledge and topics on emerging technologies will be incorporated into the curriculum.
|
0.901 |
2005 — 2009 |
Nelson, David Loren |
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. |
Fragile X Related Genes Mental Retardation/Development @ Baylor College of Medicine
DESCRIPTION (provided by applicant): This application seeks renewed funding for a joint project between the Nelson, Oostra and Paylor groups to create and study mouse models for human Fragile X syndrome. Prior aims of the project sought to develop and perform initial characterization of mice carrying conditional (Cre-lox) alleles at each of the 3 FMR1-like genes present in the mouse genome. Progress has been excellent;Fxr2 knockouts have been characterized, and models carrying conditional alleles have been created for Fmr1 and Fxr1. Double knockouts of Fmr1 and Fxr2 have been created;these show enhanced phenotypes beyond those found in the single mutants. Moreover, a unique circadian rhythm defect has been observed in double knockouts-these animals are hyperactive and show no rhythm in light/dark or dark/dark cycles. Fxr1 loss of function results in neonatal lethality, while animals with reduced levels of Fxr1 are affected, but viable. Mouse models for the human Fragile X premutation-associated tremor ataxia syndrome (termed FXTAS) have also been developed and are being characterized. These models recapitulate several aspects of this late onset neurodegenerative disorder. These studies offer the opportunity to create and characterize mouse models for genetic disorders (Fragile X syndrome and FXTAS) that result from a common human mutation. Such models will allow the determination of a number of the functions of the FMR1 class of proteins, and provide a resource for other groups interested in utilizing such models to test hypotheses regarding Fmr1 function and the consequences of its absence, as well as the newly described FXTAS disorder. This renewal request seeks to continue these studies through the pursuit of the following specific aims: 1) Development of models and assays for testing FMR1 and paralog functions in mice. 2) Development and use of mouse models to determine the mechanistic basis of Fragile X-premutation-associated tremor ataxia syndrome. Successful completion of these aims will allow the definition of function and dysfunction in Fragile X syndrome and FXTAS.
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0.958 |
2006 |
Nelson, David Loren |
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. |
Fragile X Related Genes Mental Retardiation/Development @ Baylor College of Medicine
DESCRIPTION (provided by applicant): This application seeks renewed funding for a joint project between the Nelson, Oostra and Paylor groups to create and study mouse models for human Fragile X syndrome. Prior aims of the project sought to develop and perform initial characterization of mice carrying conditional (Cre-lox) alleles at each of the 3 FMR1-like genes present in the mouse genome. Progress has been excellent; Fxr2 knockouts have been characterized, and models carrying conditional alleles have been created for Fmr1 and Fxr1. Double knockouts of Fmr1 and Fxr2 have been created; these show enhanced phenotypes beyond those found in the single mutants. Moreover, a unique circadian rhythm defect has been observed in double knockouts-these animals are hyperactive and show no rhythm in light/dark or dark/dark cycles. Fxr1 loss of function results in neonatal lethality, while animals with reduced levels of Fxr1 are affected, but viable. Mouse models for the human Fragile X premutation-associated tremor ataxia syndrome (termed FXTAS) have also been developed and are being characterized. These models recapitulate several aspects of this late onset neurodegenerative disorder. These studies offer the opportunity to create and characterize mouse models for genetic disorders (Fragile X syndrome and FXTAS) that result from a common human mutation. Such models will allow the determination of a number of the functions of the FMR1 class of proteins, and provide a resource for other groups interested in utilizing such models to test hypotheses regarding Fmr1 function and the consequences of its absence, as well as the newly described FXTAS disorder. This renewal request seeks to continue these studies through the pursuit of the following specific aims: 1) Development of models and assays for testing FMR1 and paralog functions in mice. 2) Development and use of mouse models to determine the mechanistic basis of Fragile X-premutation-associated tremor ataxia syndrome. Successful completion of these aims will allow the definition of function and dysfunction in Fragile X syndrome and FXTAS.
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0.958 |
2006 — 2010 |
Nelson, David Herman, Tim Sofer, William Goodsell, David Franzen, Margaret |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Active Learning Modules For the Molecular Biosciences @ Milwaukee School of Engineering
Biological Sciences (61)
The goal of this project is to develop a series of Active Learning Modules in which students are engaged in their own inquiry-driven exploration of the structure and function of specific proteins. The modules use physical models of proteins and other compelling visualizations that make the molecular world real to students. Each of six carefully chosen proteins is explored within the context of a case study in which the students are challenged to solve a problem that is presented against the backdrop of a current social issue. As the final component of each Module, students encounter evidence that related proteins from different organisms share a similar amino acid sequence. This recurring theme of "evolution in action" emphasizes the interrelatedness of living organisms and demonstrates the power of this fundamental concept in the molecular biosciences.
The Modules are initially piloted by the project PI and coPIs in five undergraduate institutions, and later by a larger group of undergraduate educators, many from minority-serving institutions, who are trained in the use of the Modules at two summer workshops. Assessment of student learning gains includes pre- and post-tests that include questions addressing the four major learning objectives of the Modules: (i) general concepts of protein structure and function, (ii) concepts that are specific to the topic of each module, (iii) concepts addressing the relatedness of similar proteins across different organisms, and (iv) students' attitudes toward science and its perceived importance in their lives.
Intellectual Merit. The project investigates the value of using innovative physical models and other compelling visualizations to stimulate active student exploration of the invisible molecular world. Additionally, the project measures the impact of a learning progression that first builds a deep understanding of the molecular nature of proteins and their critical role in life processes, and then presents students with data demonstrating the amino acid sequence homology of similar proteins from different organisms.
Broader Impacts. The project contributes to the growing body of education research on the use of active teaching methods to engage students in meaningful and long-lasting learning. It also seeks to change students' attitudes toward the biological sciences, especially regarding the issue of evolution, by providing examples of "evolution in action."
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0.903 |
2006 |
Nelson, David P |
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. |
The Cytoskeleton in Haart-Induced Cardiomyopathy @ Baylor College of Medicine
DESCRIPTION (provided by applicant): One of the consequences of the development of improved therapies for the treatment of HIV infection and the acquired immunodeficiency syndrome, and the associated longer survival of infected patients, has been the emergence of diseases such as myocarditis and/or dilated cardiomyopathy (DCM). A number of etiological agents have been proposed to be responsible for the initiation of the pathologic processes leading to the development of myocarditis and DCM in HIV-infected patients. These have included infection of myocytes with HIV or cardiotropic viruses, or cardiotoxicity resulting from drugs commonly used by AIDS patients, such as AZT. Monotherapy with AZT is uncommon today because highly active antiretroviral therapy (HAART) is a formidable clinical combination. However, AZT has been reported to cause a mitochondrial skeletal myopathy, similar to inherited skeletal myopathies, as well as myopathies secondary to inherited cardiomyopathies. Dystrophin was identified as the gene responsible for cardiomyopathy in patients with X-linked cardiomyopathy (XLCM). Dystrophin is thought to provide structural support for the myocyte and cardiomyocyte membrane. Mutations in dystrophin or dystrophin associated protein subcomplexes result in a wide spectrum of skeletal myopathy and/or cardiomyopathy in humans and animal models such as the mouse or hamster. We have recently shown in patients with DCM or ischemic cardiomyopathy that dystrophin remodeling is a useful indicator of left ventricular function. It has been reported that the 2A protease of Coxsackievirus B3, a major etiologic agent of acquired DCM, is capable of cleaving dystrophin, resulting in sarcolemmal disruption in infected mouse hearts. Further, in murine models of DCM defects in the integrity of dystrophin and/or other components of the cytoskeleton may be important in disease pathogenesis in these models. In order to further delineate the role of cytoskeletal disruption in models of acquired DCM we are proposing the following specific aims: Specific Aim 1: Delineation of the events leading to disruption of the cytoskeleton in transgenic mice. Specific Aim 2: Characterization of the cytoskeleton in HAART-treated transgenic mice. Specific Aim 3: Role of extrinsic stimuli in the development of HAART-induced cardiomyopathy.
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0.958 |
2008 — 2013 |
Hu, Feng Sheng Pearson, Ann (co-PI) [⬀] Nelson, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Fire, Atmospheric Pco2, and Climate as Alternative Primary Controls of C4-Grass Abundance: the Late-Quaternary Perspective @ University of Illinois At Urbana-Champaign
Grass-dominated ecosystems cover about one-third of Earth's land surface, influence global biogeochemical processes (e.g. water, carbon, and nutrient cycling), and serve as major food sources for humans and herbivores. These ecosystems are among the most sensitive to future changes in climate and atmospheric chemistry. This sensitivity can be partially attributed to the differential responses of two major functional groups, C3 and C4 plants. C4 plants gain competitive advantages under certain environmental conditions (e.g. fire, heat, drought, and low pCO2). C3 and C4 plants in turn have distinct influences on major biogeochemical processes; for example, the role of C4 plants in global net primary production is disproportionately large. Despite these well-known differences, it remains controversial what environmental factors directly control the relative abundances of C3 and C4 plants. Paleoecological studies can help decipher the responses of C3 and C4 plants to a wide range of environmental conditions, thereby offering information for anticipating future changes. This project will evaluate the effects of fire, climate, and atmospheric CO2 concentration on the variation of C4-grass abundance over the past 25,000 years in East Africa and Australia. The researchers will analyze sediment cores for a suite of ecological proxy indicators and develop a novel technique to estimate the abundance of C4 plants in geological records. This project provides an excellent context for educating the general public on climate change and grassland ecology. The researchers will organize summer courses targeting middle and high school teachers as well as land managers.
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0.903 |
2008 — 2009 |
Nelson, David Loren |
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. |
Determining Developmental Timing Requirements For Fmr1 Using Inducible Alleles @ Baylor College of Medicine
Alleles; Development; FMR1; Mental Retardation and Developmental Disabilities Research Centers; Time
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0.958 |
2008 — 2021 |
Nelson, David L |
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. P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. U54Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These differ from program project in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes, with funding component staff helping to identify appropriate priority needs. |
Administrative Core @ Baylor College of Medicine
Administrative Management; Animal Model; Animal Models and Related Studies; Animals; Assay; Award; Bioassay; Biohazard; Biohazard Substance; Biohazardous Substance; Biologic Assays; Biological Assay; CGG repeat; Compatible; Critiques; Data; Development; Disease; Disorder; Escalante syndrome; FMR1; Fmr1,; Fostering; Fragile X; Fragile X Syndrome; Funding; Genetic Alteration; Genetic Change; Genetic defect; Genetics, Human; Group Meetings; Human; Human Genetics; Human Resources; Human, General; IDDRC; IDDRP; Individual; Intellectual and Developmental Disabilities Research Centers; Investigators; MRDD Research Center; MRDDRC; Maintenance; Maintenances; Man (Taxonomy); Man, Modern; Manpower; Martin-Bell Syndrome; Martin-Bell-Renpenning syndrome; Medicine; Meetings, Group; Mental Retardation and Developmental Disabilities Research Centers; Mutation; Office of Administrative Management; Parents; Preparation; Principal Investigator; Programs (PT); Programs [Publication Type]; QOL; Quality of life; R01 Mechanism; R01 Program; RPG; Renpenning syndrome 2; Reporting; Research; Research Grants; Research Personnel; Research Project Grants; Research Projects; Research Projects, R-Series; Researchers; Schools, Medical; Science of Medicine; Services; Support of Research; Technology; Travel; Universities; X-linked mental deficiency-megalotestes syndrome; X-linked mental retardation with fragile X syndrome; X-linked mental retardation-fragile site 1 syndrome; autism-fragile X (AFRAX) syndrome; autism-fragile X syndrome; base; college; conference; cost effectiveness; disease/disorder; experiment; experimental research; experimental study; fra(X) syndrome; fra(X)(28) syndrome; fra(X)(q27) syndrome; fra(X)(q27-28) syndrome; fragile X-mental retardation syndrome; fragile Xq syndrome; fragile site mental retardation 1; fragile x [{C0016667}]; fragile x syndromes; genome mutation; human subject; improved; in vivo; interest; macro-orchidism-marker X (MOMX) syndrome; macro-orchidism-marker X syndrome; mar(X) syndrome; marker X syndrome; medical schools; mental retardation-macroorchidism syndrome; model organism; personnel; programs; research study; size; small molecule; symposium
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0.958 |
2009 — 2011 |
Nelson, David Elmore, Andrew Eshleman, Keith Peterjohn, William Mcneil, Brenden |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Mri-R2: Acquisition of a Shared Isotope Ratio Mass Spectrometer For Ecological, Geological & Hydrological Research, Education & Training in the Central Appalachians @ University of Maryland Center For Environmental Sciences
This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). Funds supplied by the NSF MRI-R2 program have helped to support the establishment of a facility for state of- the-art stable isotope measurements at the University of Maryland Center for Environmental Science Appalachian Laboratory. Acquisition of equipment for this Central Appalachians Stable Isotope Facility (CASIF) provides critical support to unique ongoing and planned research projects in multiple disciplines, including paleoecology and paleoclimatology, landscape ecology and remote sensing, biogeochemistry, hydrology & plant ecology. The funds were used to purchase a ThermoFisher Delta V+ isotope ratio mass spectrometer (IRMS), a spooling wire microcombustion device, an elemental analyzer, a high temperature conversion/elemental analyzer pyrolysis unit and a GasBench II. A critical mass of 13 new and existing faculty, including 7 early-career assistant professors who specialize in the application of isotopic and/or biogeochemical tracers are using the equipment to address pressing questions concerning the impacts of environmental change, including: long-term hydrologic variability in the flow of the Potomac River; the response of the nitrogen cycle to natural and anthropogenic perturbations; the impacts of invasive species and human activities on biogeochemical processes in soils and streams; and many other timely research topics. Together this group actively trains roughly 25 graduate students and postdoctoral researchers, and approximately 30 undergraduate researchers. Students and postdoctoral researchers, including women, minorities & first-generation students, are provided with opportunities to utilize state-of-the-art techniques and instruments at the CASIF. As a regional shared-use facility, the CASIF will promote synergistic research and education activities around common environmental-change research themes, thus enhancing intra- and inter-institution collaborations, and also helping the general public appreciate the utility of isotopes for understanding the impacts of environmental change. Results from the studies enabled by the new instrumentation will be disseminated through peer-reviewed scientific journals, and by student and faculty presentations at regional and national meetings.
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0.901 |
2009 |
Nelson, David Loren |
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 Fragile X @ Baylor College of Medicine
The organizational chart of the BCM MRDDRC is shown under section II.A.2 above (Figure II.A.1). It outlines the administrative responsibilities of the Director, the Associate Director and the Administrative Core to the Research Cores and individual research projects. Due to the number of research projects approved for access to cores in the BCM MRDDRC, we have represented them by their thematic topics, with a number in parentheses indicating the number of individual projects supported within each theme. Table II.A.2, above, lists the projects individually. Dr. Huda Zoghbi was appointed Director upon recommendation of the internal advisory committee after Dr. Edward McCabe left BCM to chair Pediatrics at UCLA. Dr. Zoghbi has been Director of the BCM MRDDRC for over eight years and will continue in that capacity. She is a board certified pediatric neurologist with abundant research accomplishments. She brings interest in and experience with numerous human genetic disorders with mental retardation as a component. She has a particular interest in Rett syndrome. Dr. Zoghbi is Professor of Pediatrics, Neurology, Neurosciences and Molecular and Human Genetics and an investigator of the Howard Hughes Medical Institute. Dr. David Nelson has served as Associate Director of the BCM MRDDRC during the current funding cycle, and will continue in that role in this proposed renewal. Dr. Nelson is a human molecular geneticist who brings extensive experience and interest in mental retardation to the MRDDRC through his activities in characterizing the fragile X syndrome, FRAXE syndrome and incontinentia pigmenti genes and their products. He also has prior experience in managing large Centers both Associate Director and Director of the NIH-funded BCM Human Genome Center. Dr. Nelson will be responsible for the BCM MRDDRC should the Director become incapacitated and he will continue to advise and assist the Director in the operation of the MRDDRC along with the Administrative and Scientific Advisory Committee.
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0.958 |
2011 — 2015 |
Nelson, David Goodsell, David Batiza, Ann Zhang, Bo Harris, Michelle |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
An Interdisciplinary Approach to Biological Energy Transfer - Cross-Institutional Collaboration and Adaptation @ Milwaukee School of Engineering
This project creates new physical models and digital instructional materials to help students understand photosynthesis, the process by which living organisms trap energy from the sun in food. During photosynthesis, green plants, algae and some microbes fix carbon dioxide from the air into organic molecules, the food upon which all living things depend. By removing carbon dioxide from the atmosphere, it also helps to control the build-up of this greenhouse gas. In addition some molecules made this way become biofuel, a renewable source of energy. Therefore this is an important process to understand. The models are used in a variety of undergraduate courses along with those previously created and tested by the SUN (Students Understanding eNergy) Project. Together these instructional materials allow undergraduates to enact both photosynthesis and cellular respiration, the process by which all living things move stored energy from food to ATP, the chemical currency required to power life. These topics are difficult for undergraduates to understand. They involve electrons moving along a particular path in protein complexes found in two cellular compartments, the chloroplast and the mitochondrion. A team from University of Wisconsin at Madison, University of Wisconsin at Milwaukee, The Scripps Research Institute, and Milwaukee School of Engineering (the lead institution) develops scale models that accurately represent the structures of the proteins involved in photosynthesis. It also creates web-based instructional materials that integrate knowledge of the biological structures with their functions. The models and digital learning tools are tested in cell biology, biochemistry, and physics classes at the cooperating institutions, and then refined for broader distribution. Ultimately they improve student learning. They also impact student persistence as science majors nationwide, since many students find these abstract concepts to be so difficult that they change their major. This project is being jointly funded by the Directorate for Biological Sciences, Division of Biological Infrastructure and the Directorate for Education and Human Resources, Division of Undergraduate Education as part of their efforts toward Vision and Change in Undergraduate Biology Education.
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0.903 |
2012 — 2014 |
Gotoh, Osamu Nelson, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Eager: Improved Computational Tools For Plant Gene Assembly and Synteny Detection @ The University of Tennessee, Memphis - the Health Science Center
The ever-increasing rate of genome sequence production will result in literally thousands of genome sequences being determined. Current automated methods for plant gene assembly have certain inherent weaknesses that result in many incorrectly assembled genes due to inaccurate detection of true intron-exon boundaries including GC boundaries, inability to detect N-terminal exons, and inappropriate fusion of adjacent genes. Expert manual annotation can usually overcome these limitations, but manual annotation is not scalable to many thousands of genes. Genome projects generally are able to claim only 1000-3000 genes were manually checked. In plant genomes this may be only 3-10% of the genes in the genome. This EAGER project seeks to improve automated plant gene assembly and annotation with a focus on cytochrome P450 genes, which comprise one of the largest gene families in plants. Successful implementation of accurate gene prediction algorithms and the development of a novel tool for identifying ohnologs (genes created by whole genome duplication events) in plant genomes will have a transformative effect on genome annotation.
This project will provide international cross-disciplinary training opportunities for one postdoctoral research associate. All programs will be available as a set of executable files from an ftp site and through the project website, both of which will be accessible via http://www.uthsc.edu/molecular_sciences/directories/faculty/d_nelson.php. The source code will also be made available at this location.
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0.901 |
2013 — 2017 |
Stylinski, Cathlyn Nelson, David Fitzpatrick, Matthew (co-PI) [⬀] Elmore, Andrew Keller, Stephen [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Combining Genomics, Remote Sensing, and Geospatial Modeling to Understand Adaptation to Growing Season Length in Balsam Poplar @ University of Vermont & State Agricultural College
PI: Stephen Keller (University of Vermont & State Agricultural College)
CoPIs: Andrew Elmore, Matthew Fitzpatrick, David Nelson, and Cathlyn Stylinski (University of Maryland Center for Environmental Science, Frostburg, MD)
Key Collaborator: Raju Soolanayakanahally (Agriculture and Agri-Food, Canada)
Translating genomic information into knowledge of environmental adaptation and prediction of performance under field conditions are core challenges facing plant biologists. The goal of this project is to associate genome-wide diversity to functional plant phenotypes using high-throughput phenotyping under field conditions and new analytical tools in balsam poplar, Populus balsamifera, a keystone tree species. This project will provide cross-disciplinary training in the latest techniques in ecological genomics, remote sensing, and spatial modeling to undergraduate and graduate students. Minority and first-generation undergraduate students will be recruited through partnerships with Frostburg State University's McNair Program and other organizations. Public outreach to rural communities will be conducted through a multi-faceted science program centered on engaging the public in the science of genomics, plant phenology, and climate change, in collaboration with the National Phenology Network (www.usanpn.org/).
This project will develop and integrate tools from genomics, remote sensing, and geospatial modeling to study the genetic basis of climate adaptation in Populus balsamifera, balsam poplar. Sampling will be focused on balsam poplar's southern range edge in order to study the physiological adaptations of populations to the warmest, earliest onset growing seasons within its geographic range. Genome-wide single nucleotide polymorphism (SNP) data will be generated for 600 poplar genotypes and used to perform genome scans for local adaptation and association mapping for phenology, growth, and water use efficiency traits. Regions of the genome associated with climate adaptation will be used to predict field performance using an independent sample of genotypes and an innovative remote sensing approach to measure phenology. New spatial analytical methods will be developed to characterize the associations between genomic variation and environmental gradients of climate and growing season length, and to visualize the landscape surface of adaptive variation under both current and projected climates. Genomic sequence data will be publically available through NCBI's sequence read archive and DOE's Knowledgebase. SNP genotypes, phenotypic traits, and remotely sensed phenology data will be publically accessible through Data DRYAD (www.datadryad.org). A software package in landscape genomics will be developed for the R project for statistical computing, and publically accessible through the Comprehensive R Archive Network (CRAN: http://cran.r-project.org/). Finally, new germplasm and associated genomic and phenotypic results will be available upon request.
|
0.934 |
2014 — 2019 |
Nelson, David Loren Samaco, Rodney C (co-PI) [⬀] Zoghbi, Huda Y [⬀] |
U54Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These differ from program project in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes, with funding component staff helping to identify appropriate priority needs. |
Baylor Intellectual and Developmental Disabilities Research Centers @ Baylor College of Medicine
? DESCRIPTION (provided by applicant): The Baylor College of Medicine Intellectual and Developmental Disabilities Research Center (BCM IDDRC) was established August 1, 1988, and has been continuously funded with the last renewal of funding July 1, 2009. The BCM IDDRC is committed to advancing research in intellectual and developmental disabilities (IDD) to address the problems encountered by individuals with IDD and their families. Specifically, the mission of the BCM IDDRC are to identify as many causes of intellectual and developmental disability as possible, to understand the mechanisms mediating these disorders, to prevent these disorders, and to provide interventions that can improve the quality of life of affected individuals and ameliorate their disability whenever possible. The specific objectives are: 1) To enhance IDD research activities at BCM by encouraging and focusing research efforts on etiology, diagnosis, prevention, mechanism of pathogenesis, and the development of therapies to treat IDD, 2) To develop and provide innovative and critical core facilities to enhance IDD research at BCM, 3) To promote a multidisciplinary approach to IDD research by improving interactions between Center investigators and recruiting new investigators into the field of IDD research, and 4) To promote scientific and collaborative interactions with investigators outside BCM who have demonstrated a major commitment to study and treat IDD. The BCM IDDRC is structured around the major themes of discovering the genetic and genomic basis of IDD, developing disease models of IDD, performing detailed pathogenesis studies of IDD, and developing novel therapies for IDD. The mission and goals of the BCM IDDRC will be accomplished by providing innovative, important, and cost-effective research core services to support high quality investigators and research projects aligned with the mission, goals, and objectives of the IDDRC. The BCM IDDRC proposes A) an Administrative Core, B) a Clinical Translational Core, C) a Rodent Neurobehavioral Core, D) a Neurovisualization Core which includes Neuropathology, Confocal, and RNA in situ, and (E) a Neuroconnectivity Core which includes Viral Production, Optogenetics, and In vivo Physiology. Additionally, the BCM IDDRC will support an innovative preclinical research project entitled Steps towards a paternal gene activation therapy for Angelman syndrome that will develop novel, genetically based treatments for that neurodevelopmental disorder. These core resources will support 45 investigators and 56 NIH funded research projects. Over the last 25 years the BCM IDDRC has been remarkably successful in fostering the discovery of the causes of IDD, determining the pathophysiology of IDD, and developing treatments for IDD. Ongoing funding will allow the Center to continue to support and expand these efforts at BCM.
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0.958 |
2014 — 2019 |
Nelson, David Loren Neul, Jeffrey L (co-PI) [⬀] Sillitoe, Roy Vincent [⬀] |
U54Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These differ from program project in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes, with funding component staff helping to identify appropriate priority needs. |
Neurovisualization @ Baylor College of Medicine
Adult; Affect; Anatomy; Architecture; autism spectrum disorder; Behavior; Brain; brain malformation; Cells; Child; college; Data; Defect; Detection; Development; Disease; Drosophila genus; Electrons; Epilepsy; Equipment; experimental analysis; Faculty; Functional disorder; Funding; Gene Expression; Gene Expression Profiling; Genetic Models; Goals; grasp; Hour; Human; human disease; Image; Image Analysis; In Situ Hybridization; in vivo; Individual; innovation; Institutes; intellectual and developmental disability; knowledge base; Label; Laboratories; Lead; Maps; Medicine; Mental Retardation and Developmental Disabilities Research Centers; Microscope; Microscopic; Microscopy; Mission; mRNA Expression; Nerve Degeneration; neural circuit; Neurologic; Neurons; neuropathology; Pattern; Population; Postdoctoral Fellow; Preparation; Process; relating to nervous system; Reporter; Research Institute; Research Personnel; research study; Resolution; Resources; RNA; robot assistance; Role; Science; Services; Signal Transduction; skills; Staining method; Stains; Structure; Students; Synapses; Technology; Time; Tissue Embedding; Tissue Sample; Tissues; Training; translational study; Transmission Electron Microscopy; two-photon; Work;
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0.958 |
2014 — 2019 |
Nelson, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Career: Karrikin and Strigolactone Signaling Mechanisms in Arabidopsis @ University of Georgia Research Foundation Inc
DAVID C NELSON PROPOSAL IOS-1350561 CAREER: Karrikin and strigolactone signaling mechanisms in Arabidopsis
Karrikins are a recently discovered class of compounds found in smoke that activate germination of many plant species after fire. Strigolactones comprise a family of plant hormones that regulate shoot branching, root architecture, and cambial growth. Strigolactones also trigger germination of the highly destructive parasitic weeds, broomrape and witchweed, and promote symbiotic associations with arbuscular mycorrhizal fungi. Understanding the molecular mechanisms by which karrikins and strigolactones control plant growth may enable a new wave of innovation in crop development and weed control.
Plants recognize both karrikins and strigolactones through a genetic pathway that requires the F-box protein MAX2. F-box proteins have central roles in several plant hormone signaling systems, and act by targeting specific protein substrates for degradation. The targets of MAX2 have long remained elusive and as such represent a critical roadblock to understanding the mechanism of karrikin and strigolactone signaling. A genetic screen has now led to the identification of a candidate target, SUPPRESSOR OF MAX2 1 (SMAX1), which regulates seed germination and seedling growth. SMAX1 is a member of an uncharacterized family of eight genes in the model plant Arabidopsis thaliana. In this project genetic and biochemical approaches will be used to determine 1) how other genes in the SMAX1 family contribute to plant development; 2) the molecular function and regulation of SMAX1 protein; and 3) the protein interacting partners of SMAX1 and MAX2. These experiments will reveal how the SMAX1 family acts in karrikin and strigolactone signaling and whether SMAX1 is a target of MAX2.
A postdoctoral researcher,graduate student, and several undergraduates will be trained for careers in science-related fields. Two projects will be initiated to improve undergraduate retention in science-related careers and enhance K-12 STEM education. The discoveries from this project will be disseminated through publications in peer-reviewed journals and presentations at scientific conferences.
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0.915 |
2014 — 2019 |
Arenkiel, Benjamin R. [⬀] Nelson, David Loren Neul, Jeffrey L (co-PI) [⬀] |
U54Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These differ from program project in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes, with funding component staff helping to identify appropriate priority needs. |
Neuroconnectivity Core @ Baylor College of Medicine
Animals; Behavior; Behavioral; Brain; brain tissue; Cell Communication; Cell Culture Techniques; cell type; Clinical; cost; cost effective; Custom; Data; Dependovirus; design; Disease model; Engineering; engineering design; Experimental Designs; flexibility; Functional disorder; gain of function; Gene Expression; genetic approach; Genetic Engineering; genetic manipulation; Goals; Image; In Vitro; in vivo; Individual; insight; Intellectual functioning disability; Investigation; Knowledge; Laboratories; Life; Light; Maps; member; Mental Retardation and Developmental Disabilities Research Centers; Methods; Molecular; Molecular Biology; mouse model; Nerve Tissue; nervous system disorder; Nervous System Physiology; neural circuit; neuronal patterning; Neurons; neurophysiology; Neurosciences; neurotropic; neurotropic virus; optogenetics; Pattern; Preparation; Process; Production; programs; Property; Proteins; Reagent; Relative (related person); Reporter; Research; Research Personnel; Rodent Model; Services; Slice; small hairpin RNA; Subfamily lentivirinae; Synapses; synaptic function; Technology; Testing; Time; Tracer; Transgenic Mice; Transgenic Organisms; vector; Viral; Viral Vector; virus genetics;
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0.958 |
2014 — 2019 |
Nelson, David Loren Neul, Jeffrey L (co-PI) [⬀] Paylor, Richard E |
U54Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These differ from program project in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes, with funding component staff helping to identify appropriate priority needs. |
Neurobehavioral @ Baylor College of Medicine
The objectives of the BCM IDDRC Neurobehavioral Core are three-fold. The first is to provide training in the rigorous performance of mouse behavioral assays. The second goal is to provide priority access to the Neurobehavioral Core facilities for BCM IDDRC investigators interested in identifying and characterizing behavioral abnormalities in mice carrying mutations relevant to IDD. BCM IDDRC investigators will have two options available to them for the behavioral analyses of their mutant mice. Investigators will be able to either test their own mice, or they will be able to utilize core services to perform behavioral analyses for them on a collaborative basis with Dr. Paylor's group for either mutant mice or newly developed mutant rats (1). This latter strategy is referred to as a collaborative core service. The third objective of the Neurobehavioral Core is to provide training in experimental design and statistical analyses that is customized for the mutant mouse behavioral analyses. While the ability of laboratories to use genetic and molecular techniques for generating mutant mouse models of intellectual disabilities has become more routine, the ability to perform comprehensive analyses of the behavioral responses of these mutant mice is still expensive, requires numerous pieces of specialized equipment and specially designed laboratory space. Perhaps most significant, appropriate training in the design of studies and analysis of the resultant data (along with use of the equipment) is necessary to generate high quality and reproducible results. It is the goal of the Neurobehavioral Core to provide access to state of the art facilities that are equipped with specialized equipment for behavioral studies. It also provides rigorous training to ensure successful analysis of mutant mice generated by BCM IDDRC investigators. In addition, a collaborative service is available to those BCM IDDRC investigators interested in having the testing performed for them in collaboration with Dr. Paylor. The collaborative model applies, in particular, to the newly developed rat genetic models that are already being analyzed and are likely to be advanced in the coming years. The BCM IDDRC Neurobehavioral Core will provide BCM IDDRC investigators with a battery of assays that will offer initial insight into the behavioral consequences of specific mutations. In addition, the Neurobehavioral Core will also provide access and training on the use of additional behavioral assays that will allow a BCM IDDRC investigator to perform critical secondary or follow-up studies important to better understand the nature of any behavioral abnormality detected with a primary behavioral test battery. The Neurobehavioral Core of the BCM IDDRC is well established in studying the behavioral responses of mutant mice. The Core has been in operation for more than 15 years, since the original recruitment of Dr. Paylor. Dr. Paylor was involved in the initial studies of behavioral effects in a knockout mouse model in 1991, and has since evaluated the behavioral effects of over 200 different mutations in lines of mice. Most recently, he has characterized 7 mutations resulting in gene knockouts in rats, which are now possible with the use of TALEN and CRISPR methods for generating genetic lesions. Shortly after joining BCM, Dr. Paylor became the Director for the BCM IDDRC Neurobehavioral Core. His laboratory developed and utilizes a comprehensive set of behavioral assays to evaluate a wide range of responses in mutant mice and his skills and experience have been translated to the Neurobehavioral Core. Dr. Corinne Spencer is the Co-Director for the BCM IDDRC Neurobehavioral Core. She joined the Neurobehavioral Core approximately 8 years ago and has quickly become a major strength of the Core by providing management of the day-to-day operation of the Core, training investigators on various items of equipment, the development and validation of new testing assays, and training users in best practices for rigorous and reproducible behavioral studies in the mouse. Users of BCM IDDRC Neurobehavioral Core have access to a wide array of behavioral assays (see below) to assess numerous domains of CNS function. The Core has been incredibly successful during the previous funding period as measured by the number of users, hours of use, and publications by a variety of users. Moreover, the Core continues to expand its ability to assess behavioral responses of mutant mice and now rats, responding to increasing needs and desires of BCM IDDRC investigators.
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0.958 |
2014 — 2019 |
Lee, Brendan Nelson, David Loren Neul, Jeffrey L (co-PI) [⬀] |
U54Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These differ from program project in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes, with funding component staff helping to identify appropriate priority needs. |
Clinical Translational @ Baylor College of Medicine
Achievement; Adherence; Advisory Committees; Animal Model; Area; base; Basic Science; bench to bedside; biobank; Biological; Biological Markers; biomarker discovery; Clinic; Clinical; Clinical Investigator; Clinical Research; Clinical Trials Unit; Collaborations; Collection; college; cost effectiveness; Coupled; Data Quality; Diagnosis; driving force; Environment; experience; Generations; Genes; Genetic; Genomics; Good Clinical Practice; Human; Human Subject Research; improved; insight; Institutes; Intellectual functioning disability; Laboratories; Lesion; Manuscripts; Medicine; Mental Retardation and Developmental Disabilities Research Centers; Mentors; Molecular; Neurodevelopmental Disorder; novel therapeutics; Organization administrative structures; patient biomarkers; Patient Care; Patients; Performance; Phenotype; Positioning Attribute; prevent; Process; Proteomics; Protocols documentation; Publishing; Research; Research Activity; research clinical testing; Research Infrastructure; Research Personnel; research study; Resources; Sampling; Scientist; Services; success; Supervision; System; Techniques; Testing; Time; transcriptomics; Translating; Translational Research; translational scientist; Translations; trial design; Validation;
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0.958 |
2014 — 2019 |
Beaudet, Arthur L. [⬀] Nelson, David Loren Neul, Jeffrey L (co-PI) [⬀] |
U54Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These differ from program project in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes, with funding component staff helping to identify appropriate priority needs. |
Steps Towards a Paternal Gene Activation Therapy For Angelman Syndrome @ Baylor College of Medicine
Adolescent; Adult; Age; Alleles; Angelman Syndrome; Animals; Antisense Oligonucleotide Therapy; Antisense Oligonucleotides; Antisense RNA; base; Binding; Biological Markers; Birth; Body Fluids; Brain; brain morphology; Cell Culture Techniques; Cell model; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Data; design; Development; developmental disease/disorder; Diagnosis; Dose; drug development; Evaluation; Fibroblasts; Funding; Gene Activation; Genes; Genetic Transcription; Genomic DNA; Genotype; Goals; Government; Histopathology; Human; imprint; improved; induced pluripotent stem cell; Intellectual functioning disability; knock-down; Life; Measures; Mediating; Mental Retardation and Developmental Disabilities Research Centers; metabolomics; Methods; Molecular Genetics; mouse model; Mus; Mutation; Neuraxis; Neurodevelopmental Disorder; Neurologic Examination; Neurons; Oligonucleotides; optimism; Patients; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase I Clinical Trials; Phenotype; Plasma; preclinical study; Proteomics; Provider; Research; Route; Schedule; Sequence Homology; Skin; Spinal Muscular Atrophy; Staging; Technology; Testing; Therapeutic Index; Therapeutic Intervention; therapy development; Time; Tissues; transcriptomics; Wild Type Mouse;
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0.958 |
2015 — 2021 |
Nelson, David Loren |
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. |
Training Program in Cell and Molecular Biology @ Baylor College of Medicine
Project Summary/Abstract This application is the fifth competing renewal of the sole training grant supporting the Integrative Molecular and Biomedical Sciences Graduate Program (IMBS) at Baylor College of Medicine. The IMBS Program was funded on a commitment to excellence in research, with strict guidelines for both student and faculty participation in the program. The Program currently involves 106 participating faculty from multiple institutions throughout the Texas Medical Center. This dynamic mix of established investigators and newly recruited young faculty with diverse research interests allows IMBS students to train with world-class scientists and select from a wide spectrum of exciting research possibilities. During the 24 years of funding, 250 students have entered the program, with 80 students currently enrolled. Of the 170 trainees who have left the Program, 122 received their Ph.D., 17 received Master's degrees, and 31 withdrew or transferred. We have consistently attracted high caliber students to the Program using active recruitment strategies. Increased institutional support during this funding period has allowed us to increase the entering class size over the past four years from 9 to 16 students per year. We continue to emphasize a rigorous graduate education program, combined with intensive, personalized mentoring throughout all stages of IMBS graduate training. The research productivity of IMBS students has been exceptional, as measured by both the number and quality of student-authored publications. Students who graduated from the Program, between 2009 and 2013, have extremely strong publication records. These 44 students published, on average, 3.4 papers resulting from their thesis research, 1.4 of which were first author papers, with an average impact factor of 8.8 per publication. An additional notable achievement during the last funding period has been our continued success in both recruiting, and retaining, underrepresented minority (URM) students, with 11 URM students (14%) currently enrolled in the program. In addition, our current URM IMBS students include some of the top students in the College with regard to academic achievements. During the previous training period, 10 predoctoral positions were funded through this award. We are requesting an increase to 12 funded positions in the current renewal, based on our established track record of recruiting and training top students who take science leadership positions in academia, industry and government. We plan to maintain an enrolled student body of ~80 students, an optimal size for scientific interactions and mentoring by Program faculty.
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0.958 |
2016 — 2019 |
Nelson, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Discovery of a Novel Signal That Enhances Germination and Seedling Growth @ University of Georgia Research Foundation Inc
Plant hormones control how and when plants grow, and how plants react to their environment. Manipulating plant hormones with chemical and genetic tools has been instrumental in the green revolution; a deeper understanding of how hormones control plant growth will likely fuel future advances in agriculture. In this project, biological sensors will be developed to detect a recently recognized plant hormone called strigolactone, and an unknown molecule in plants (KL) that controls seed germination, seedling growth, and leaf shape. The biological sensors will be used in this project to purify KL, which may be a novel hormone, and to identify genes that produce it. Discovery of KL may lead to the development of new agrichemicals or genetic modifications that promote uniform seed germination and seedling vigor, thus increasing crop yields. Strigolactone sensors will be useful tools for plant breeders to more easily develop crops with altered strigolactone levels, which can in turn influence the fertilizer requirements of crops and their susceptibility to weeds. Undergraduate students and a postdoctoral researcher will be trained in research skills and scientific communication, leading to enhancement of the scientific workforce. Research discoveries will be communicated to the public through journal publications, press releases, news articles, and local speaking opportunities.
Karrikins are compounds found in smoke that promote seed germination after fire and enhance seedling vigor. The karrikin signaling pathway is highly similar to the strigolactone signaling pathway, suggesting common ancestry. A receptor that is necessary for karrikin responses, KARRIKIN INSENSITIVE 2 (KAI2), has been identified, but karrikins are unlikely to be its native ligand. The aims of this project are to (1) develop sensitive and specific biological assays to detect the unknown KAI2 ligand (KL) and strigolactones, (2) identify genes involved in KL biosynthesis, and (3) highly purify KL from plant extracts as a steppingstone toward its identification. Biological sensors for karrikins/KL and strigolactones based on transcriptional or proteolytic responses will be engineered. These bioassays will be used in genetic screens to identify KL-deficient mutants. Finally, bioassay-guided fractionation will be used to isolate KL in small molecule extracts from plants. The discovery of KL and KL biosynthesis genes will catalyze a new field of research in plant biology that impacts the understanding of seed dormancy, seedling photomorphogenesis, and leaf development. It will also provide insights into the ancestral function of the KAI2 signaling mechanism in basal land plants, which later duplicated and evolved to mediate growth control by strigolactones.
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0.915 |
2016 — 2017 |
Nelson, David Loren |
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.) |
Improved Mouse Models to Study Fragile X Associated Primary Ovarian Insufficiency @ Baylor College of Medicine
? DESCRIPTION (provided by applicant): Spontaneous 46,XX primary ovarian insufficiency (POI) affects as many as 1 in 100 women by the age of 40. The most common genetic cause identified for 46,XX POI is heterozygosity for the Fragile X (FX) premutation, In FXPOI, ovarian insufficiency results from increased follicular atresia in the ovaries of FMR1 premutation (CGG lengths from 60-200 repeats) carriers; however, the mechanism(s) that result in this atresia remain unclear. POI encompasses the spectrum of ovarian dysfunction from early indicators of ovarian failure, such as infertility and elevated levels of follicle-stimulating hormone, to featurs of overt ovarian failure, including irregular menstrual cycles. Understanding the role of the FMR1 premutation allele in ovarian dysfunction is critical to improving current assisted reproductive technologies and developing new therapeutic strategies. In this application, we propose to develop mouse models that will allow studies of the rCGG's role in FXPOI. Determining whether ectopically expressed premutation-length CGG repeat tracts are sufficient to confer POI is critical to understanding the role of rCGG in the pathogenesis of FXPOI. We propose to generate and study new mouse models designed to generate FXPOI pathology and capable of determining the role(s) of rCGG, FMR1 as well as tissue specificity of expression. Two aims are proposed: In Aim 1, we will create four new FXPOI mouse models. Two experimental models will contain a human genomic DNA fragment with a 90 repeat CGG tract upstream of a heterologous ZsGreen1 transcript (CGG90- ZsGreen1) or a human FMR1 cDNA. The targeting vectors will also include a loxP-flanked transcriptional/ translational STOP sequence (LSL) to allow for spatial and/or temporal control of expression of CGG repeat RNA using tissue-specific or drug-dependent Cre excision. Two control models will be created without the 90 repeat CGG to determine the specificity of rCGG to phenotypes. These models will allow us to assess the requirement of the FMR1 transcript in mediating pathology, and enable us to determine whether specific phenotypes associated with FXPOI originate from expression of rCGG in specific tissues of the hypothalamic- pituitary-gonadal axis and to compare these with those resulting from widespread expression. In Aim 2, we propose to study mice expressing the introduced constructs for features of FXPOI. We will compare our models for phenotypes observed in existing models that broadly express FMR1-coupled rCGG transgenes. We propose to count and determine quality of follicles in time course studies and to measure a variety of hormone levels for alterations from normal levels. We will also measure FMR1 mRNA and protein. We anticipate that these models will be of significant interest to the research community for additional studies of FXPOI, FXTAS and other phenotypes that result from rCGG repeat, and expect to distribute them widely.
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0.958 |
2017 — 2019 |
Quade, Jay (co-PI) [⬀] Dettman, David [⬀] Nelson, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Development of Tunable Infrared Laser Direct Absorption Spectroscopy (Tildas) For Clumped Isotope Analysis of Co2
This project is enabling the University of Arizona, University of Washington, and private sector partner Aerodyne Research to develop a next-generation laser spectroscopy system to measure combinations of carbon and oxygen isotopes that are known as "clumped isotopes." The new technology will enable researchers to study the earth's past climate at lower cost, with smaller sample sizes, and in greater numbers than is currently possible by mass spectrometry. The new instrument will make possible a large increase in the number of proxy measurements of past earth temperatures because it eliminates the need for separate estimates of oxygen isotopes. Such a system is expected to be adopted quickly by laboratories around the world for application to geologic, oceanographic, biologic, and atmospheric samples.
This project links the University of Arizona and the University of Washington with Aerodyne Research in improving the precision of Aerodyne's Tunable Infrared Laser Direct Absorption Spectroscopy (TILDAS) system to make clumped isotope measurements of carbon dioxide that are competitive with current techniques using mass spectrometry. The key measurement is of the different isotopic combinations of carbon dioxide, such as carbon 13, oxygen 18, and oxygen 16. The ability to analyze samples that are 30 to 80 times smaller means that higher spatial resolution can be obtained to allow research into better time resolution such as that afforded by seasonally-banded shells. Other research opportunities include the ability to study soil processes and Holocene paleoclimate using layered soil carbonates from the Andes and northwestern US; seasonality and carbon cycle during the Early Eocene Climatic Optimum and Cretaceous greenhouse from lake and soil carbonates; and the detailed history of fluid-fault interactions, cross cutting relationships and multiple fluids preserved in calcite veins from paleo and active fault zones and hydrothermal systems.
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0.907 |
2017 — 2020 |
Nelson, David Fitzpatrick, Matthew [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Evolutionary Responses to Environmental Change At Range Limits: Adaptation, Migration and Population Size At the Core, Margin and Trailing Edge @ University of Maryland Center For Environmental Sciences
Biologists lack a general understanding of the interaction between changes in climate and variation in abundance, connectivity, and local adaptation from the center to the edge of species' ranges. By the end of the 21st century, temperatures are predicted to rise 3-5 degrees C across much of temperate and boreal North America, causing populations of many species to face climate conditions beyond their current tolerances. Mathematical models predict that evolution in response to environmental change can depend critically on how close populations are located to the edge of their range, yet little is known empirically about how responses to this environmental change vary spatially across a species' distribution, especially near range limits. This research uses an ecologically and economically important forest tree in eastern North America, red spruce (Picea rubens), to study the effects of range limits on responses to environmental change. The project addresses the overarching question: how do shifting range limits driven by environmental change affect adaptation, migration, and population size across a species' distribution? Addressing this problem advances our scientific understanding of adaptation at range limits and the processes that constrain species distributions. In addition, this work addresses a pressing applied problem of how environmental change will affect the productivity of natural and human-managed ecosystems located in marginal environments. Additional broader impacts include assessing the conservation status of southern populations of a foundation tree species in eastern coniferous forests at risk of local extinction. The results will be shared with diverse stakeholders working on forest conservation and management, and will be integrated with assessments of local population vulnerability and the design of informed mitigation efforts. Local citizens in rural communities will be engaged through public science outreach. This award will also serve to train two postdoctoral researchers, one graduate student, and numerous undergraduate researchers in evolutionary ecology, plant physiology, and environmental change science.
The experimental approach of the research will leverage species distribution modeling to track historical range movements in red spruce over the last 11,000 years, and predict proximity to the shifting range limit for different locales. These predictions will then be related to the changing size, connectivity, and ecophysiology of populations experiencing environmental change by sampling fossil spruce pollen preserved in sediment and using recent advances at the interface of paleoecology and population genetics to measure plant water use efficiency, effective population size, and connectivity through time. The research will also couple the latest techniques in ecological genomics with novel spatial modeling approaches to predict how local adaptation will vary with proximity to the range limit under scenarios of projected climate warming in North America.
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0.901 |
2018 — 2019 |
Nelson, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Graduate Research Fellowship Program (Grfp) @ University of Maryland Center For Environmental Sciences
The National Science Foundation (NSF) Graduate Research Fellowship Program (GRFP) is a highly competitive, federal fellowship program. GRFP helps ensure the vitality and diversity of the scientific and engineering workforce of the United States. The program recognizes and supports outstanding graduate students who are pursuing research-based master's and doctoral degrees in science, technology, engineering, and mathematics (STEM) and in STEM education. The GRFP provides three years of financial support for the graduate education of individuals who have demonstrated their potential for significant research achievements in STEM and STEM education. This award supports the NSF Graduate Fellows pursuing graduate education at this GRFP institution.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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0.901 |
2020 — 2021 |
Nelson, David Loren Samaco, Rodney C (co-PI) [⬀] Zoghbi, Huda Y [⬀] |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Baylor College of Medicine Intellectual and Developmental Disabilities Research Center @ Baylor College of Medicine
PROJECT SUMMARY/ABSTRACT: The Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at Baylor College of Medicine (BCM IDDRC) has been instrumental in advancing basic science, translational, and clinical endeavors to improve the lives of individuals with intellectual and developmental disability (IDD). Beyond discoveries, the Center has mentored more than two generations of scientists and physicians engaged in research and the care and treatment of individuals with IDD. The mission of the BCM IDDRC is to identify as many causes of IDD as possible, to understand their pathogenesis, and to develop novel diagnostic and therapeutic approaches. To realize this mission, accelerate the research activities of our Investigators and advance development of therapeutics for IDD, we will carry out the following aims: 1) Provide Core facilities and services to advance IDD research. Six cores are proposed to provide innovative, high-quality and cost-effective research services to assist investigators in studies of molecules (Molecular and Expression Analysis), cells and tissues (Cell and Tissue Pathogenesis), circuits (Circuit Analysis and Modulation), and whole organisms (Preclinical and Clinical Outcomes). The Clinical Translational Core will provide services specific for clinical research infrastructure and the Center Administration Core will coordinate overall Center operations along with stakeholder engagement, communication and education; 2) Promote and enhance collaborative efforts and dissemination activities with a comprehensive engagement, communication, and education plan. The Admin Core will promote interactions locally, nationally, and internationally, will implement best practices for community partnerships and dissemination of research findings, and will enhance the training of next-generation IDD researchers; 3) Conduct a multidisciplinary signature research project that leads to clinical trial readiness. The emergence of DNA-based therapies, coupled with exciting discoveries and preclinical studies from the BCM IDDRC, provides exciting opportunities to treat IDDs, but the fact that many IDD-causing genes are dosage sensitive (too much or too little is detrimental) poses a serious challenge requiring robust biological markers meaningful for the individual rather than the population. The Signature Project seeks to develop multidimensional biomarkers (molecules and circuits) for target engagement, safety, and efficacy in six gene dosage dependent IDDs. The Center will support 75 investigators and 72 research projects. For 30+ years the BCM IDDRC has had a profound impact on IDD, elucidating causes, determining mechanisms, and developing interventions. It has fostered an environment that welcomes and supports additional investigators and emphasizes training. As we enter the next decade, Center investigators, their collaborators, and trainees are poised to transform dozens of exciting discoveries into safe therapeutics that will improve the quality of life and well-being of individuals with IDD.
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0.958 |
2021 |
Nelson, David Loren Todd, Peter K |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Fragile X Premutations, Mechanisms and Modifiers @ Baylor College of Medicine
Fragile X Premutations- Mechanisms and Modifiers Fragile X-associated disorders are a heterogeneous group of conditions arising from alterations in the size, content, and epigenetic state of a polymorphic CGG repeat within the FMR1 gene. Described as the first repeat expansion disorder nearly 30 years ago, FMR1 CGG repeat expansions are both an important cause of neurological, reproductive and neurodevelopmental disease as well as an archetype for understanding repeat expansions and the mechanisms by which they elicit dysfunction. Work over past decades delineated the native functions of the fragile X protein, FMRP, and the consequences of its loss and the explored toxic gain-of function mechanisms (RNA-mediated toxicity via protein sequestration, and protein mediated toxicity from Repeat associated non-AUG (RAN) translation) elicited by transcribed CGG repeats. Despite these efforts, we still lack effective therapies for any of the cardinal Fragile X- associated disorders. Here we propose a paradigm shift in our approach to FX associated disorders. Rather than focusing solely on specific diseases (Fragile X Syndrome (FXS), fragile X-associated tremor/ataxia syndrome (FXTAS), and fragile X-associated primary ovarian insufficiency (FXPOI)), the Center structure enables us to directly engage the mechanistic cross-talk between conditions and between the FMR1 locus and related repeat expansion disorders. Our central hypothesis is that a deeper understanding of genetic factors which underlie clinical disease onset and penetrance in premutation associated disorders and an exploration of native CGG repeat functions will reveal novel insights into both how repeats cause disease and how they might be targeted therapeutically. Led by a multidisciplinary team featuring many leaders in the Fragile X field, we will address this hypothesis in three cohesive projects all focused on premutation disorders by using data-driven genomic and bioinformatics approaches coupled with emerging tools and integrative model systems. By pooling our substantial data, expertise and resources, we will pursue a deeper understanding of FX premutation pathogenic mechanisms and define a series of robust and viable targets for therapeutic development across Fragile X-associated disorders.
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0.958 |
2021 |
Nelson, David Loren |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Fxtas: Mechanisms and Modifiers @ Baylor College of Medicine
SUMMARY Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder that affects individuals with premutation alleles (55?~200 CGG repeats) in fragile X mental retardation 1 (FMR1). Common features of FXTAS include progressive intention tremor, gait ataxia, Parkinsonism, and cognitive decline. Penetrance is age-dependent and reaches ~75% in male carriers by age 80. Up to ~15% of women with premutations also show symptoms of FXTAS. The neuropathological hallmarks of FXTAS include ubiquitin- positive intranuclear inclusions throughout the brain and marked dropout of Purkinje neurons in the cerebellum. At the molecular level, FMR1 premutation alleles exhibit a 2 to 8-fold increase in FMR1 mRNA and expression of mutant mRNAs containing long (~100) CGG triplets has been shown to be toxic in cell and animal models. Current data support two non-mutually exclusive molecular pathogenesis mechanisms for FXTAS: 1) RNA gain- of-function, in which the expression of expanded CGGs in RNA (rCGG) interferes with a subset of RNA-binding proteins (RBPs), functionally limiting their availability through sequestration, and 2) Repeat-associated non-AUG (RAN) translation, whereby translation through the rCGG (and/or antisense rCCG) repeats leads to the production of toxic homo-polypeptides, the most abundant of which is FMRpolyGlycine (FMRpolyG), that in turn interfere with cellular functions. Multiple mouse models have been developed and used by us and others to study these mechanisms. Previous work by the Nelson, Todd, Allen and Jin groups using model organisms (flies, mice) and cell models has identified several RBPs affected by expression of rCGGs. Among these are Pur ?, hnRNP A2/B1, DROSHA/DGCR8, and TDP43. Increasing expression of these proteins can modulate rCGG-mediated toxicity in model systems, supporting the RNA-mediated sequestration model of FXTAS. In addition, RAN translation products are found in patient inclusions and mouse models and appear to also confer toxicity in numerous studies. In studies to determine the contributions of both the RAN translation and RBP sequestration mechanisms to FXTAS pathogenesis, we have generated transgenic lines of mice that express hnRNP A2/B1 and suppression of rCGG repeat-mediated toxicity without alteration of FMRpolyG positive inclusions. Parallel efforts at the Emory Fragile X Center used whole genome sequence (WGS) analysis of premutation carriers with early or late onset of FXTAS, combined with fly genetic screens to identify additional genetic modifiers that influence age of onset of FXTAS. Understanding the role of variation in these genes could suggest candidate therapeutic targets. In this application, we propose to confirm and extend identification of genetic modifiers through sequence analysis and analyze potential modifiers of FXTAS identified at Emory using human genetics and model system studies at Baylor, Emory and Michigan using additional fly, cell and mouse models. In coordination with Projects 1 and 3, we expect to improve understanding of mechanisms that lead to FXTAS and other Fragile X-associated Disorders, such as Fragile X associated Primary Ovarian Insufficiency (FXPOI).
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0.958 |