Current Research

Noncoding cis-Regulatory Sequence Evolution

Shared motif method (SMM) Illustration of the shared motif method (SMM)
Differences in gene expression between species may entail changes in spatial, temporal, and environmental dimensions. The genetic basis of such changes and how they evolve is currently not known. By identifying the types of cis-regulatory changes that affect quantitative changes in gene expression between species we aim to elucidate some of the general rules that underlie gene regulation. Toward this end we combine different types of genomic expression and sequence data to model how cis-regulatory sequence change and gene expression are related.

Gene Network Evolution

Gene network
Networks of interacting genes are responsible for generating life's diversity. Gene networks play a central role in our sophisticated immune response, the ability to digest food, and even for causing cancer - the disaster that occurs when gene networks become un-regulated. Thus understanding the properties of gene networks is of fundamental importance in the post-genomic era.

However, very little is known about already well-characterized genetic networks. Outstanding and fundamental questions include: How much natural variation is present in gene networks among individuals? Among species? What is the genetic basis for such differences? Do certain parts of gene networks change their ability to tolerate variation (mutational insult) over evolutionary time?

The comparison of a well-understood gene network among related species is a powerful way to gain insight into these questions. Each species represents a natural experiment and, when compared, can shed light on the structure, dynamics, and function of a gene network. Our goal is ambitious: to discover general principles underlying gene network function, variation and evolution.

To do this, we use a combination of statistical and computational techniques coupled with molecular genetic experiments in the fruit fly, Drosophila melanogaster and its relatives. The fruit fly is our chosen organism of study because of the powerful molecular and genetic tools available to manipulate this organism. The genomes of 11 other species in the genus Drosophila have recently been sequenced. These species span a range of 3 million to 40 million years in relationship to one another. The ability to compare the genomes and phenotypes of multiple fly species provides an oppotunity to determine how gene networks function and evolve.