Waterston, Robert

With the increasing number of available complete genome sequences, the challenge shifts to understanding how the stored information is interpreted to enable life. We are exploring ways to contribute to the understanding of the genome of the nematode worm, C. elegans.

C. elegans offers unique advantages in understanding the regulatory circuitry that underpins development. The ability to follow the invariant pattern of cell divisions in real time offers an opportunity to describe gene expression patterns of single cells at minute time resolution. To exploit this property, we have automated the determination of the lineage, and we can overlay any pattern of gene expression from a transgenic fluorescent reporter construct on the lineage pattern. We have determined expression patterns for more than 150 embryonically expressed transcription factors.  In addition to accumulating expression patterns for more transcription factors we using the available data to predict and test regulatory interactions.

As part of the NHGRI modENCODE project we are using RNAseq to refine gene models and to describe gene expression patterns in detail.  We have collected data for all the major stages of the life cycle and are currently determing expression for a detailed embryonic time course.  We are also applying RNAseq to determine mRNA content of different cell types in the embryo and larval stages. 

Exploiting the increasing capacity of next generation sequencing we are generating full sequence of 2,000 mutatgenized strains.  These will contain about 700,000 point mutations, with multiple alleles of almost all genes.  Beyond providing mutations for genes of interest to the community, we are developing novel approaches to use the resource to understand gene interactions in C. elegans.