Development of high-throughput genotype-phenotype associations in zebrafish
Our lab is highly interested in developing systematic understanding of the relationship between genes and environment using high throughput, phenotype-driven genetic and chemical screens in the zebrafish. Our interest ranges from the most primitive cellular behaviors to more complex pathophysiological processes. Taking advantage of the scalability and rapid development of the zebrafish, we have used these startegies to study gene-gene and gene-environment interactions in development and in disease biology. Recently we used this approach to identify chemical suppressors of different genetic causes of heart failure, and we are now using the initial ‘hit’ compounds to explore new therapies for these conditions. We are now expanding these efforts to undertake ‘co-clinical’ modeling of specific disease genes with a view to rapid pathway insights and capturing real time insight for individual patients.
We have also developed a systematic approaches to predicting gene-phenotype relationships based on iterative in silico modeling and in vivo validation. These studies have demonstrated that efficient prioritization in zebrafish can accelerate the pace of gene function discovery.