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 genetic, cell biology and genomic/ computational approaches. Our
research addresses three fundamental questions:
1.) What are the pathways, dynamics and
principles of adaptive evolution 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.
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.
3.) What is the high-resolution structure of
genetic interaction networks? 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.
Areas of Research/Interest
Genomics of adaptive evolution, growth-rate regulation and post-transcriptional gene regulation.
Publications
A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds.
Nat Biotechnol (2009 Apr)
Ho CH, Magtanong L, Barker SL, Gresham D, Nishimura S, Natarajan P, Koh JL, Porter J, Gray CA, Andersen RJ, Giaever G, Nislow C, Andrews B, Botstein D, Graham TR, Yoshida M, Boone C |
Coordination of growth rate, cell cycle, stress response, and metabolic activity in yeast.
Mol Biol Cell (2008 Jan)
Brauer MJ, Huttenhower C, Airoldi EM, Rosenstein R, Matese JC, Gresham D, Boer VM, Troyanskaya OG, Botstein D |
Email update requests to
fas.bio.computing@nyu.edu
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