We have the ultimate goal of characterizing gene expression dynamics in developing C. elegans embryos. In an effort to characterize the differences in mRNA content between individual embryonic cells, Dr. Nishimura characterized the individual transcriptomes of the first two zygotic daughter cells using single-cell RNA-seq [Osborne Nishimura et al., 2015]. She later contributed to a collaborative effort to characterize the transcriptomes of all cells produced through the first four cell divisions [Tintori et al., 2016]. Interestingly, the transcriptomes of even the earliest C. elegans cells begin to diversify despite the fact that de novo transcription does not initiate at those stages.

How do differences in mRNA abundance arise? Our group hypothesized that post-transcriptional mechanisms such as differential mRNA stabilization, transport, inheritance, or decay drive the patterning. Interestingly, we have found that mRNA transcripts with cell-specific patterns of enrichment often accumulate in interesting regions within the cell! This was a big surprise. Our current research seeks out the mechanisms directing mRNA to concentrate in different regions of the cell. We also want to understand the reason why these transcripts accumulate in different locales

Our efforts led to recent insights into how and why mRNA transcripts concentrate into P granules (biomolecular condensates important for germline function. We found that transcripts move to P granules dependent on their translational repression [Parker et al., 2020] and directed by signals in their 3'UTR regions that impede translation, suggesting that P granules scavenge messages undergoing low to no translation. Current work in the lab is investigating mechanisms that direct mRNA localization to membranes.

All intestines digest food, but the intestine of the C. elegans nematode worm undertakes additional tasks that, in humans, are performed by separate organs. This includes coordinating fat storage, growth, genetic aging, environmental stress, and response to infection. At only 20-cells, the C. elegans intestine is a model of developmental genetics. In it, a network of GATA transcription factors directs intestinal cell fate by culminating in the expression of ELT-2 (Erythroid Like Transcription factor), the major intestinal regulator. This network has been instrumental in revealing general aspects of network biology, but critical gaps remain and we have yet to satisfyingly link it to the various tasks the intestine accomplishes once formed. Our research seeks to rectify unexplained aspects of the regulatory network and to expand the network to integrate stages of development when the intestine performs multiple functions.