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Designing and interpreting large-scale experiments to understand pathway
structure and its relationship to phenotype and human disease.
Current experimental interests:
- Exploiting parallel sequencing technology to phenotype all pairwise
gene deletion combinations in S. cerevisiae, with initial application
to genes involved in transcription.
- Generation of S. cerevisiae strains carrying dozens of chosen
targeted deletions, with initial application to delete all ABC
transporters imparting multidrug resistance.
- Targeted insertion of gene sets encoding entire human pathways into
S. cerevisiae, with initial application to genes involved in drug
metabolism.
Current computational interests:
- Systematic analysis of genetic interacton to reveal redundant
systems and order of action in genetic pathways.
- using knockout, knockdown, overexpression or other
genetic perturbations of combinations of genes in S. cerevisiae,
C. elegans or mouse.
- Using genome-scale genotyping of natural polymorphisms in
S. cerevisiae and human populations.
- Integrating large-scale studies — including phenotype,
genetic epistasis, protein-protein and transcription-regulatory
interactions and sequence patterns — to quantitatively assign
function to genes and guide experimentation and disease
association studies.
- Alternative splicing and its relationship to protein
interaction networks.
Information on positions available in the Roth lab.
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