Gresham:Research

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(Systems biology of cell growth and quiescence)
 
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== Current Research ==
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== Research ==
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Our aim is to understand the structure and behavior of the genetic networks that interpret the external environment of the cell.  We use the budding yeast to study these networks using a combination of genetics, cell biology and genomic/computational approaches.  Our research addresses three fundamental questions:
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The Gresham lab studies the regulation of cell growth and the regulation of mRNA decay.  We use the budding yeast (''Saccharomyces cerevisiae'') as a model system and a combination of genetic, genomic and computational methods to address these questions.
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1) What are the pathways, dynamics and principles of adaptive evolution in response to environmental conditions? In order to investigate how genetic networks evolve in response to environmental conditions we perform evolution experiments over hundreds of generations in defined environments using chemostat (continuous) cultures.  We study the multigenic basis of evolved quantitative phenotypes to understand the evolutionary trajectories of fitness landscapes and how genes interact to produce quantitative variation. 
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== ''Systems biology of cell growth and quiescence'' ==
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2) How does post-transcriptional regulation of gene expression facilitate response to environmental conditions? The response of biological networks to dynamic environments requires processes that occur on very short timescales.  The fastest means of altering transcriptional programs is through the degradation or stabilization of pre-existing transcripts.  We study the mechanisms that regulate the fate of RNAs in response to environmental signals. 
 
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3) What is the high-resolution structure of genetic interaction networks? In order to build a map of genetic interactions we employ high throughput suppressor screens using conditional lethal alleles.  We use forward and reverse genetic approaches to explore a large fraction of sequence space allowing us to identify both those genes (and their products) that interact and the sequence specificity of those interactions. Our ultimate aim is to infer the rules that govern the interaction and co-evolution of genes.
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We are interested in the regulation of cell growth and how it is coordinated with progression through the cell cycle, metabolism and the synthesis and degradation of macromolecules.  To control the growth rate of cells we use chemostats, which allows us to systematically study the metabolic, physiological and molecular programs associated with different rates of cell growth.  We are taking a variety of approaches to study how cell growth is regulated including:<br>
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-the study of mutants with increased growth rates selected from long term nutrient-limited chemostats <br>
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-mapping QTL that underlie variation in growth rate in natural isolates of yeast<br>
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-using massively parallel phenotyping to identify genetic networks that regulate cell growth and quiescence.<br><br>
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== ''Regulation of mRNA decay'' ==
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The fastest way to remodel global transcriptional states is to regulate the stability of existing populations of messenger RNAs. In response to particular extracellular stimuli we have found that the half-life of specific transcripts is dramatically decreased. We are studying how the fate of mRNAs is regulated using:<br>
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-''in vivo'' labeling of mRNAs<br>
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-kinetic studies of mRNA synthesis and decay<br>
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-identification of ''cis'' and ''trans'' factors that alter mRNA decay rates  <br><br>

Current revision

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Research

The Gresham lab studies the regulation of cell growth and the regulation of mRNA decay. We use the budding yeast (Saccharomyces cerevisiae) as a model system and a combination of genetic, genomic and computational methods to address these questions.

Systems biology of cell growth and quiescence

We are interested in the regulation of cell growth and how it is coordinated with progression through the cell cycle, metabolism and the synthesis and degradation of macromolecules. To control the growth rate of cells we use chemostats, which allows us to systematically study the metabolic, physiological and molecular programs associated with different rates of cell growth. We are taking a variety of approaches to study how cell growth is regulated including:

-the study of mutants with increased growth rates selected from long term nutrient-limited chemostats

-mapping QTL that underlie variation in growth rate in natural isolates of yeast

-using massively parallel phenotyping to identify genetic networks that regulate cell growth and quiescence.

Regulation of mRNA decay

The fastest way to remodel global transcriptional states is to regulate the stability of existing populations of messenger RNAs. In response to particular extracellular stimuli we have found that the half-life of specific transcripts is dramatically decreased. We are studying how the fate of mRNAs is regulated using:

-in vivo labeling of mRNAs

-kinetic studies of mRNA synthesis and decay

-identification of cis and trans factors that alter mRNA decay rates

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