Gunsalus and Piano Lab

The main focus of our research centers on the key broad question of how the genome directs early animal development. We have used a variety of genome-wide approaches to elucidate the genetic architecture of molecular networks underlying complex developmental programs. We are interested not only in the roles that specific genes play, but also how groups of genes and interactions of pathways work together to ensure that embryos develop properly.

Using the animal model C. elegans, we generated the first molecular map of early embryonic development (Gunsalus et al., Nature 2005). This work demonstrated a modular architecture of molecular machinery by identifying groups of genes that share phenotypes, interact with each other, and are co-expressed across a variety of conditions. In collaboration with the Oegema lab at UCSD, we extended the map to include an earlier developmental stage, the germline, which revealed how some of the same molecular components are reused for different cellular processes during different stages of development (Green et al., Cell 2011).

The integrated embryo network illustrated that interconnected molecular modules form the basic functional units within molecular networks and led us to shift our overall focus from individual genes to molecular modules and their functional relationships. An emergent theme from these early studies was the idea that the loss of function of most genes can be buffered through compensatory mechanisms. It is now clear that many diseases are caused by context-dependent genetic interactions rather than mutations in individual genes. As a result, small individual differences can lead to highly variable responses to treatments for diseases like cancer. Thus, gaining a global perspective on the functional dependencies within genetic networks is an important goal in understanding complex genetic systems, with direct relevance to human health.