| Our laboratory develops
new machine learning techniques and algorithms to model the transcriptional
regulatory networks that control gene expression programs in living cells.
We have a very productive interdisciplinary collaboration with leading biologists
that has allowed us to tackle extraordinarily difficult and interesting
problems that underlie cellular function and development. For example, we
have developed probabilistic models of cellular function (PSB),
built a comprehensive model of the yeast cell cycle (Science
2002), participated in the discovery of the draft transcriptional regulatory
code of yeast (Nature 2004), and helped
uncover how key diabetes related transcription factors regulate cellular
function in the human pancreas and liver (Science
2004). Current work in our laboratory is examining how we can computationally
model chromatin modifying complexes that are associated with the genome
of living yeast cells. New kinds of mechanistic computational models are
necessary to capture how chromatin structure encodes cellular memory, and
how the state of this memory is used to control gene expression. In particular,
we are investigating new modular graphical models that use mechanistic constraints
to describe biological mechanism.
A new focus is an interdisciplinary project that seeks
to build computational models of the transcriptional regulatory networks
that control the differentiation of specific cell types. Elucidating these
regulatory networks will enable us to define the regulatory processes
that determine a cell's progress to its terminally differentiated state,
and position us to differentiate embryonic stem (ES) cells for the treatment
of debilitating human diseases. New computational techniques for elucidating
transcriptional regulatory networks based on the integration of diverse
high-throughput experimental data (genome sequence, chromatin structure,
transcription factor-DNA binding, gene expression) provide a powerful
foundation for discovering the detailed mechanisms of regulatory network
control of cell differentiation during development.
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