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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15GM083309-01A1
Application #
7516086
Study Section
Nuclear Dynamics and Transport (NDT)
Program Officer
Carter, Anthony D
Project Start
2008-09-01
Project End
2009-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
1
Fiscal Year
2008
Total Cost
$32,890
Indirect Cost
Name
University of Southern Mississippi
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
623335775
City
Hattiesburg
State
MS
Country
United States
Zip Code
39406
Sarma, Nayan J; Willis, Kristine (2012) The new nucleoporin: regulator of transcriptional repression and beyond. Nucleus 3:508-15
Sarma, Nayan J; Buford, Thomas D; Haley, Terry et al. (2011) The nuclear pore complex mediates binding of the Mig1 repressor to target promoters. PLoS One 6:e27117