The early C. elegans embryo is a powerful model to study the global genetic architecture underlying development. During the current funding period we have (1) identified most of the genes required for all visible processes during early embryonic development using large-scale RNAi followed by analysis of time-lapse recordings;(2) built a global view of the molecular complexes required for early embryogenesis by integrating high-resolution phenotypes with other functional genomic data;and (3) explored the properties of the map by studying the function of several new proteins. For example, we have found that MEL-28 plays an essential role coordinating nuclear envelope and kinetochore functions in the early embryo. In the current proposal we aim to extend these studies to identify the role of proteins beyond the essential ones and to identify how the essential complexes are coordinated and functionally linked with one other. We have developed a high-throughput system for genome-wide RNAi to identify suppressor and enhancer interactions using existing conditional alleles. Using ~30 alleles of representative genes from diverse processes in the early embryo, we aim to apply this approach to build a global scaffold of suppressor and enhancer interactions in the early embryo. We expect that the identification and analysis of these genetic interactions will extend dramatically our view of the genes working in the early embryo and how they interact to coordinate biological processes. Elucidating these mechanisms will help further our understanding of complex phenotypes underlying human disease. 1 7. Narrative A fundamental question, now that the human genome sequence has been elucidated, is to understand how it directs complex biological and development programs in both normal and disease states. Over the last few years we have made progress in deciphering the single gene requirements in many basic developmental processes but we have a very limited view of how multi-gene interactions affect these programs. Since most human diseases arise from complex effects of multiple interacting components it is imperative that we gain insights into these mechanisms. We will conduct genome-wide analyses to uncover genetic interactions required during the early developmental programs in the genetic model C. elegans. The resulting map will help us understand complex genetic networks underlying development and disease in humans. 1

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Coulombe, James N
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
New York University
Schools of Arts and Sciences
New York
United States
Zip Code
West, Sean M; Mecenas, Desirea; Gutwein, Michelle et al. (2018) Developmental dynamics of gene expression and alternative polyadenylation in the Caenorhabditis elegans germline. Genome Biol 19:8
Weicksel, Steven E; Mahadav, Assaf; Moyle, Mark et al. (2016) A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in C. elegans. Development 143:3540-3548
Gómez-Saldivar, Georgina; Fernandez, Anita; Hirano, Yasuhiro et al. (2016) Identification of Conserved MEL-28/ELYS Domains with Essential Roles in Nuclear Assembly and Chromosome Segregation. PLoS Genet 12:e1006131
Chen, Jia-Xuan; Cipriani, Patricia G; Mecenas, Desirea et al. (2016) In Vivo Interaction Proteomics in Caenorhabditis elegans Embryos Provides New Insights into P Granule Dynamics. Mol Cell Proteomics 15:1642-57
Fernandez, Anita G; Mis, Emily K; Lai, Allison et al. (2014) Uncovering buffered pleiotropy: a genome-scale screen for mel-28 genetic interactors in Caenorhabditis elegans. G3 (Bethesda) 4:185-96
Stoeckius, Marlon; Grün, Dominic; Kirchner, Marieluise et al. (2014) Global characterization of the oocyte-to-embryo transition in Caenorhabditis elegans uncovers a novel mRNA clearance mechanism. EMBO J 33:1751-66
Cicconet, Marcelo; Gutwein, Michelle; Gunsalus, Kristin C et al. (2014) Label free cell-tracking and division detection based on 2D time-lapse images for lineage analysis of early embryo development. Comput Biol Med 51:24-34
Mizrak, Dogukan; Ruben, Marc; Myers, Gabrielle N et al. (2012) Electrical activity can impose time of day on the circadian transcriptome of pacemaker neurons. Curr Biol 22:1871-80
Fernandez, Anita G; Bargmann, Bastiaan O R; Mis, Emily K et al. (2012) High-throughput fluorescence-based isolation of live C. elegans larvae. Nat Protoc 7:1502-10
Gunsalus, Kristin C; Rhrissorrakrai, Kahn (2011) Networks in Caenorhabditis elegans. Curr Opin Genet Dev 21:787-98

Showing the most recent 10 out of 33 publications