Office: Mrb 239
Phone: (970) 491-6233
- Ph.D., University of California, Berkeley
- B.S. University of California, Santa Cruz
The genome is the blueprint of the body... ...but it is unclear how genetic information is accessed to produce the shape and form of the body. Biologists have long sought to determine how transcriptomes – the sets of mRNA transcripts – change during embryogenesis in an attempt to gain insight into this question.
Why is this hard to study? With the advent of high throughput genome sequencing, it should be possible to map how transcriptomes change through embryogenesis. However, it is difficult to obtain enough material from specific cell types for use in genomic assays. Further, it is often difficult, in most animals, to link a transcriptome profile from cells in an early stage of development to their eventual fates in a later stage.
How does our lab meet these challenges? Using hand dissection coupled with low-input RNA-seq, we have generated cell-specific transcriptome profiles in early embryonic stages of the nematode worm, C. elegans. To link these genome-wide assays to specific developmental fates, we rely on the determinant property of C. elegans development. C. elegans embryos produce an invariant number of cells that divide with highly reproducible timing and certain fate allowing us to link embryonic cells in early stages to their eventual fates.
A complementary approach: In addition to using high-resolution genomic assays, we also use high-resolution microscopy (smFISH) to observe individual molecules of mRNA transcripts with sub-cellular resolution in nematode embryos. This technique allows us to test for factors (sequences and proteins) required for mRNA regulation.
Projects: We are currently focused on the following research objectives:
- Identifying mechanisms responsible for mRNA patterning prior to the onset of zygotic transcription and in its earliest stages
- Assessing the functional significance of cell-specific mRNAs
- Identifying general features of lineage-specific transcriptional activation
- Hand Dissection of <em>Caenorhabditis elegans</em> Intestines Journal of Visualized Experiments, 187.
- It’s Just a Phase: Exploring the Relationship Between mRNA, Biomolecular Condensates, and Translational Control Frontiers in Genetics.
- The ERM-1 membrane-binding domain directs erm-1 mRNA localization to the plasma membrane in the C. elegans embryo Development, 22, 2022.
- Hyper-active RAS/MAPK introduces cancer-specific mitotic vulnerabilities Proceedings of the National Academy of Sciences, 41, 2022.
- Improved Methods for Single-Molecule Fluorescence In Situ Hybridization and Immunofluorescence in Caenorhabditis elegans Embryos Current Protocols.
- The transcription factor ELT-2 positively and negatively impacts direct target genes to modulate the Caenorhabditis elegans intestinal transcriptome BioRXiV, 2021.
- LCD-Composer: an intuitive, composition-centric method enabling the identification and detailed functional mapping of low-complexity domains. NAR genomics and bioinformatics, 2, 2021.
- Improved methods for protein and single-molecule RNA detection in C. elegans embryos BioRXiV, 2021.
- mRNA localization is linked to translation regulation in the Caenorhabditis elegans germ lineage. Development (Cambridge, England), 2020.
- YTHDF2 destabilizes m6A-modified neural-specific RNAs to restrain differentiation in induced pluripotent stem cells. RNA (New York, N.Y.), 2020.
- mRNA localization is linked to translation regulation in the Caenorhabditis elegans germ lineage BioRXiv, 2020.
- Widespread roles for piRNAs and WAGO-class siRNAs in shaping the germline transcriptome of Caenorhabditis elegans. Nucleic acids research, 2019.
- TIR domains of plant immune receptors are NAD+-cleaving enzymes that promote cell death Science, 6455, 2019.
- A Strategy To Isolate Modifiers of Caenorhabditis elegans Lethal Mutations: Investigating the Endoderm Specifying Ability of the Intestinal Differentiation GATA Factor ELT-2. G3 (Bethesda, Md.), 5, 2018.
- Quantitating transcription factor redundancy: The relative roles of the ELT-2 and ELT-7 GATA factors in the C. elegans endoderm. Developmental biology, 2, 2018.
- TIR-only protein RBA1 recognizes a pathogen effector to regulate cell death in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America, 10, 2017.
- A Transcriptional Lineage of the Early C. elegans Embryo Dev Cell, 4, 2016.
- Polar Positioning of Phase-Separated Liquid Compartments in Cells Regulated by an mRNA Competition Mechanism Cell, 6, 2016.
- Probing and rearranging the transcription factor network controlling the C. elegans endoderm Worm, 3, 2016.
- The function and regulation of the GATA factor ELT-2 in the C. elegans endoderm Development, 3, 2016.
- Asymmetric transcript discovery by RNA-seq in C. elegans blastomeres identifies neg-1, a gene important for anterior morphogenesis PLoS Genet, 4, 2015.
- RNA-seq in the tetraploid Xenopus laevis enables genome-wide insight in a classic developmental biology model organism Methods, 3, 2014.
- The enigmatic conservation of a Rap1 binding site in the Saccharomyces cerevisiae HMR-E silencer G3 (Bethesda), 12, 2012.
- Symmetry, asymmetry, and kinetics of silencing establishment in Saccharomyces cerevisiae revealed by single-cell optical assays Proc Natl Acad Sci U S A, 4, 2011.
- The establishment of gene silencing at single-cell resolution Nat Genet, 7, 2009.
- Maize mutants lacking chloroplast FtsY exhibit pleiotropic defects in the biogenesis of thylakoid membranes Plant Cell, 1, 2004.
- Toward a systems approach to understanding plant cell walls Science, 5705, 2004.
- WIN1, a transcriptional activator of epidermal wax accumulation in Arabidopsis Proc Natl Acad Sci U S A, 13, 2004.
- Group II intron splicing factors derived by diversification of an ancient RNA-binding domain EMBO J, 15, 2003.
- Microspore separation in the quartet 3 mutants of Arabidopsis is impaired by a defect in a developmentally regulated polygalacturonase required for pollen mother cell wall degradation Plant Physiol, 3, 2003.