Research Interests

We study the genetic and evolutionary mechanisms underlying early embryonic development using functional genomics approaches in C. elegans and related nematodes.  One of our major goals has been to use RNA interference (RNAi) of ovary-expressed genes followed by time-lapse microscopy to identify the embryonic function of C. elegans genes.  RNAi offers a powerful way to obtain information about the loss-of-function phenotypes, while the early embryo offers a system in which basic cellular and developmental processes can be studied in great detail.  We currently have tested over 1,000 genes and identified about 300 genes required for embryogenesis.  Although most of these genes are highly conserved, fewer than 10% have been identified in classic genetic screens.  We use the data obtained from the RNAi tests to build gene clusters based on phenotypes.  The clusters are then used to guide two broad lines of investigation:  (1) functional analysis of the genome, and (2) molecular dissection of specific cellular processes. 

From the initial studies, we have found groups of genes required for basic processes such as nuclear movements, mitotic spindle formation, cytokinesis, cell cycle progression, and proper asymmetric cell division.  In many cases, these clusters contain genes that are conserved in humans.  However, their function in humans is not yet known.  Therefore, our data can be used not only to analyze the C. elegans genome but also to guide the functional examination of the human genome.  In our current dataset we have already found genes for which the human homolog is associated with a genetic disease, including some that have been previously targeted for anti-cancer drug development.  We analyze specific genes by looking at their localization pattern and dissecting how they affect cellular and subcellular processes in the early embryo.

In a related project we are using the early nematode embryo as a model to study the evolution of developmental mechanisms.  Comparisons across species have revealed fundamental differences during early embryogenesis.  Significantly, in some species the wild-type patterns of early cleavages resemble those produced by specific C. elegans mutants.  We are examining these phenotypic differences in conjunction with molecular analyses to identify mechanisms underlying the phenotypic diversity seen in nature.