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Professor of BiologyProfessor of
Office: 202 BBEIowa City, IA 52242
Email: email@example.comWeb: More About Dr. Fassler - Related Websites and Resources
BS, Micro., Comms. Arts, Cornell UniversityPhD, Biology, Purdue UniversityRockefeller UniversityHarvard University
Biosciences Graduate ProgramInterdisciplinary Graduate Program in GeneticsInterdisciplinary Graduate Program in InformaticsInterdisciplinary Graduate Program in NeuroscienceInterdisciplinary Graduate Program in Translational BiomedicineMedical Scientist Training Program
"Molecular Genetics of Signal Transuction and Transcriptional Activation in Yeast
All cells modulate the levels at which specific genes are expressed under different conditions. In single-celled organisms the capacity for regulation of gene expression enables successful adaptation to the environment. In multi-cellular organisms regulation of gene expression is the key to complex developmental programs. Modulation of gene expression in response to the environment has at least three components: (1) external signals are recognized and converted into information that can be transmitted to genes in need of regulation (signal transduction); (2) DNA binding proteins with the ability to activate transcription (transcriptional activators) recognize specific DNA binding sites in the regulatory regions of appropriate genes; and (3) transcriptional activators trigger transcription by interacting with the transcriptional machinery. Our research uses molecular, genetic and biochemical techniques in investigating the mechanics of transcriptional activation in response to external stimuli using the single-celled eukaryote, Saccharomyces cerevisiae (yeast).
We are studying an interesting type of signal transduction pathway in yeast. This pathway mediates the response of yeast cells to osmotic stress and may mediate a response to additional environmental signals as well. Molecular characterization of the SLN1 gene by our lab revealed a high degree of similarity to the common ""two-component"" signaling system in prokaryotes. The SLN1 signaling pathway consists of a histidine/aspartate phosphorelay in which phosphate is transferred from a histidine residue to an aspartate residue in one protein (the ""transmitter) to a histidine residue in a second protein (the ""phosphorelay protein') to aspartate in a final ""receiver"" protein. We found that the SLN1 signaling pathway is branched. The transmitter and phosphorelay proteins are shared, but there are two receiver proteins. One activates a second signal transduction cascade, ultimately activating a set of osmotic response genes. The other receiver protein enters the nucleus, binds to DNA and activates genes involved in control of cell growth . We found that the two branches of the pathway are reciprocally regulated. When the activity of one branch is increased, the activity of the other is decreased. This suggests cells may need to coordinate the osmotic response with aspects of cell growth.
Using genetic screens, we have identified some of the signaling molecules involved in each of the two branches, learned more about the stimulus, and identified some of the target genes of the SLN1 pathways. In collaboration with Dr. Deschenes' laboratory (Dept. of Biochemistry, Univ. of Iowa), we have developed an in vitro system for examining phosphorylation of the intermediate proteins. Using these approaches we are in the process of addressing the following and other interesting questions about the pathway: (1) how is information transferred between molecules of the pathway? (2) what additional environmental signals activate the pathway? and (3) how are the two branches of the pathway related?"
Date Last Modified: 08/04/2015 -
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