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Within the decade, sequencing a person's DNA will cost just a few thousand dollars, compared with the billions of dollars spent sequencing the first human genome.
But as personalized genome sequencing becomes a common medical procedure, how will medicine sort through that vast pool of information to deliver health benefits?
Aimée Dudley's group at ISB is trying to answer this question using a branch of systems biology known as systems genetics.
Instead of examining the effects of genes one by one, the lab studies how networks of genes interact to shape the traits of an organism.
These investigations can reveal, for example, how the unique genetic sequences in each person can affect an individual's susceptibility to a
disease or response to a medical therapy. They can also determine how the interactions among a limited number of genes can give rise to a
very broad array of biological traits.
To understand gene interactions at this level, researchers must study large numbers of individuals that are genetically distinct.
Dudley's group uses yeast as a model system, since yeast have less than one-third as many genes as humans yet exhibit many of the same
biochemical pathways as more complex organisms. Dudley and her collaborators use a collection of more than 200 strains of yeast isolated
from six continents, including yeast used in wine making, sake production, and baking; yeast infecting immunocompromised people; and yeast
from natural sources, such as palm fronds, oak trees, and insects. The research team mates different strains to produce thousands of
recombinant progeny. The wide range of genetic variation produced through these crosses is comparable to the range of variation found in
populations of other organisms, including humans. Using a wide range of automated, robotic technologies the lab generates and automatically
assays thousands of recombinant progeny in order to measure the responses of the organism to combinations of genetic and environmental perturbations.
These responses are then analyzed to probe the interactions between genes, and the results are used to build models of genetic systems.
Recently, the group has focused on how genetic variation affects posttranscriptional mechanisms of gene regulation -- and specifically the
consequences of variation for protein-RNA complexes called P-bodies that regulate translation and mRNA degradation.
Dudley's work on P-bodies grew out of a broader interest in the mechanisms of gene regulation and a collaboration with computer
scientists including Daphne Koller's group at Stanford University. An algorithm the group has developed identifies groups of genes
whose expression is statistically correlated with mutations in regulatory factors. The method has broad applications, including predicting
polymorphisms in humans responsible for phenotypic effects.
As with much of the work being done at ISB, research in Dudley's lab is inherently collaborative. Besides working with many of the other
faculty groups at ISB, she works with groups at Washington University in St. Louis, Boston University, and the University of British Columbia
on topics including genetics, automated image analysis, mathematical modeling, and microfluidic based technologies. In particular, the adoption
and adaptation of new technologies have been critical components of her research. This approach requires a unique blend of biological understanding
and engineering expertise.
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Group Personnel |
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Research Scientist
Dani Vinh
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Postdoctoral Fellow
Cecilia Garmendia
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Graduate Student
Gregory Cary
Zhihao Tan
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Research Associate 2
Michelle Hays
Adrian Scott
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Research Associate 1
Amy Sirr
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Lab Assistant
Sean Michael
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Bioinformatics Scientist
Gareth A Cromie
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Lab Manager
Cathy Ludlow
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Visiting Scholar
Patrick May
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Project Coordinator
Theresa Fitzgerald
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