Genetic Interaction Networks in Development
An organism’s fitness is determined by the coordinated action of gene networks. While some heritable diseases arise from mutations in individual genes, most arise from genetic interactions between multiple loci. We are using the nematode C. elegans to investigate how genes interact with each other to influence early development in this simple animal model system. Comprehensive gene knock-down studies have revealed that only around 15% of genes are essential on their own, whereas over half of annotated protein-coding genes are expressed in any individual cell. Therefore, we are particularly interested in learning about how non-essential genes contribute to essential developmental processes.
To study the architecture of genetic interactions in early development, we have developed a high-throughput (HTP) approach that combines genetically sensitized strains with RNAi to identify genetic modifiers of essential genes (Cipriani and Piano, 2011). So far, we have performed genome-wide screens for enhancers and suppressors of 24 temperature-sensitive alleles of genes with essential roles in the early embryo. Our HTP screening platform is aided by an image analysis algorithm we have developed called DevStaR, which uses computer vision and machine learning to quantify the survival rates of progeny in mixed populations of animals (White et al., 2013).
These studies are revealing how the embryo balances different competing demands, such as the generation of energy vs. the production of materials required during the rapid cell divisions that take place early in development.