2005 — 2006 |
Willis, Kristine Amalee |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Ms Inbre Usm: Functional Genomics Facility @ University of Southern Mississippi
functional /structural genomics
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1 |
2008 — 2010 |
Willis, Kristine Amalee |
R15Activity Code Description: Supports small-scale research projects at educational institutions that provide baccalaureate or advanced degrees for a significant number of the Nation’s research scientists but that have not been major recipients of NIH support. The goals of the program are to (1) support meritorious research, (2) expose students to research, and (3) strengthen the research environment of the institution. Awards provide limited Direct Costs, plus applicable F&A costs, for periods not to exceed 36 months. This activity code uses multi-year funding authority; however, OER approval is NOT needed prior to an IC using this activity code. |
Movement of Regulated Genes to the Nuclear Periphery
[unreadable] DESCRIPTION (provided by applicant): The long term objective of this project is to understand the relationship between the regulation of gene expression and nuclear substructure. Recent reports indicate that, soon after they are transcriptionally induced, genes in the model eukaryote Saccharomyces cerevisiae move to the nuclear periphery and associate with nuclear pore complexes. Specific Aim 1 is to use a single cell assay for regulated gene expression to determine the relationship between perinuclear gene anchoring and the ON and OFF transcriptional states. Specific Aim 2 is to explore the possibility that movement to the nuclear periphery is a universal property of transcriptionally induced genes. If not it will be important to determine whether transcriptionally active genes not anchored at the nuclear periphery become anchored elsewhere in the nucleus, for example within the nucleolus. Understanding these and other related aspects of gene regulation is key to the development of effective therapeutics for human diseases, since improperly regulated transcription is often responsible for congenital disorders and cancer. For example, the neurodegenerative disease spinocerebellar ataxia 7 results from a trinucleotide expansion in the SCA7 subunit of the chromatin modifying TFTC complex. These studies will take advantage of the integrated approach, including genetic, cell biological, and biochemical analyses, that is possible in the S. cerevisiae model system. The ease with which this organism can be grown and manipulated also makes it an ideal choice in providing research opportunities for undergraduate students. PUBLIC HEALTH RELEVANCE: The long-term objective of this project is to understand the relationship between the regulation of gene expression and nuclear substructure. Understanding these and related aspects of gene regulation is key to the development of effective therapeutics for human diseases, since improperly regulated transcription is often responsible for congenital disorders and cancer. [unreadable] [unreadable] [unreadable]
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0.948 |
2011 |
Willis, Kristine Amalee |
R15Activity Code Description: Supports small-scale research projects at educational institutions that provide baccalaureate or advanced degrees for a significant number of the Nation’s research scientists but that have not been major recipients of NIH support. The goals of the program are to (1) support meritorious research, (2) expose students to research, and (3) strengthen the research environment of the institution. Awards provide limited Direct Costs, plus applicable F&A costs, for periods not to exceed 36 months. This activity code uses multi-year funding authority; however, OER approval is NOT needed prior to an IC using this activity code. |
Movement of Induced Genes to the Nuclear Periphery
DESCRIPTION (provided by applicant): Recent analyses have shown that many eukaryotic genes change position or mobility when induced. These changes occur independently in each cell in a population, but to date gene expression has been measured as an average across many thousands of individuals or as a frozen instant in time in a single fixed cell. These limitations have complicated analysis of the relationship between gene position, mobility, and transcription. To address this problem, we have developed a reporter assay that allows convenient and simultaneous monitoring of both the position and expression of a given gene in a single living cell. As a result, we have discovered that deletion of MIG1, the extensively-studied repressor of approximately 300 glucose-regulated genes in the model eukaryote Saccharomyces cerevisiae, has a profoundly asymmetric effect on expression from the promoter of its archetypical target SUC2;repression is lost in only half of all cells, and transcription remains fully inhibited in the other half. The goal of Specific Aim 1 is to determine whether these two populations are truly distinct, or if individual cells can switch between populations. If switches occur, we will determine what relationship, if any, exists between gene position and changes in expression state. The goal of Specific Aim 2 is to identify the molecular mechanism or mechanisms that mediate repression of SUC2 in the absence of MIG1. Understanding glucose-regulated gene expression is key to the development of effective therapies for diabetes, metabolic syndrome, and cancer;the conserved AMP kinase pathway, which operates upstream of Mig1, has been implicated in all of these diseases. The studies described here will apply genetic, cell biological, biochemical, and genomic techniques, thereby making full use of the integrative approach to problem solving that is available in the S. cerevisiae model system. The ease with which this organism can be grown and manipulated also makes it an ideal choice in providing research opportunities for undergraduate students. PUBLIC HEALTH RELEVANCE: Understanding glucose-regulated gene expression is key to the development of effective therapies for diabetes, metabolic syndrome, and cancer. The AMP kinase (AMPK) pathway, which responds to the presence of glucose in eukaryotic organisms from yeast to humans, controls the function of numerous transcription factors. The long-term objective of this project is to understand how nuclear organization contributes to the regulation of genes targeted by the AMPK pathway.
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0.948 |