We seek to understand how are the properties of an organism – its development, physiology and behavior – are encoded in its genome. We primarily use molecular genetics of the nematode Caenorhabditis elegans but also apply proteomics, computational biology, biochemistry, cell biology, imaging, behavioral analysis, optogenetics, synthetic biology to not only C. elegans but also parasitic nematodes most notably Steinernema hermaphroditum, budding yeast, mice, jellyfish, fungi, and human cells as needed.
Specific areas of current interest are:
- How does the 302-neuron worm brain assess the future environment based on computation of sensory and physiological inputs?
- Does the male worm have a neural representation of its mating partner?
- How to worms navigate up a chemical gradient?
- How can we best predict gene expression from DNA sequence?
- What are the functional consequences of variants found in individual with autism spectrum disorder and other human phenotyps?
- How do cells migrate accurately during development?
Our major strategy is to perturb the activity of one or more genes and measure how cells or animals misbehave to infer gene function and genetic pathways. We measure gene expression by RNA-seq and transgenic reporters; we measure behavior using automated systems and optogenetics. We focus on intercellular signals and their transduction by the responding cell into transcriptional outputs. Many of the genes we have identified are the nematode counterparts of human genes, and we are leveraging C. elegans molecular genetics to study human genes with no actionable information and of the consequence of variants found in human individuals, including those with autism spectrum disorder. Nematodes are major health and agricultural problems, so we focus on parasite relevant biology such as dauer/infective juvenile development, using genomics and molecular genetics.
Lab News
Aidyl is honored as an Explorer!
New Alliance Release with new Textpresso full text, single sentence, ontology-based search.
Mark Zhang successfully defended his Ph.D. thesis! See preprint of chapter 2
New paper on WormBase transition and Nick's paper on improving enrichment analysis
Paul Sternberg was awarded Thomas Hunt Morgan Medal of the Genetics Society of America.
Xuan Wan applied her expertise in analyzing chemotaxis as part of an interdisciplinary team to improve anti-bacterial catheters, as described on the Caltech site and a recent paper in Science Advances.
We have a collection of cGAL drivers for C. elegans sensory neurons and additional effectors, described in a new team paper in the PNAS spearheaded by Stephanie Nava, Wilber Palma and Xuan Wan.
Drs. Hillel Schwartz and James Tan cloned a mutant locus in the insect-killing Steinernema hermaphroditum! A just published paper describes this first such success. The Dumpy mutants defective in this gene were discovered by Hillel, James, and two summer students, Jackeline Peraza and Krystal Raymundo.
The Global Biodata Coalition announces its first list of Global Core Biodata Resources. Our very own WormBase and the Alliance of Genome Resources are both included! See the article in The Caltech Weekly here.
Caltech Green Labs was co-founded by former lab manager Sarah Torres
Enrichment analysis: Markarian N, Van Auken KM, Ebert D, Sternberg PW. Enrichment on steps, not genes, improves inference of differentially expressed pathways. PLoS Comput Biol. 2024 Mar 25;20(3):e1011968. doi: 10.1371/journal.pcbi.1011968. PMID: 38527066; PMCID: PMC10994554.
Cloning genes in Steinernema! Schwartz HT, Tan CH, Peraza J, Raymundo KLT, Sternberg PW. Molecular identification of a peroxidase gene controlling body size in the entomopathogenic nematode Steinernema hermaphroditum. Genetics. 2023 Dec 11:iyad209. doi: 10.1093/genetics/iyad209. Epub ahead of print. PMID: 38078889.
Many more cGAL reagents! Nava S, Palma W, Wan X, Oh JY, Gharib S, Wang H, Revanna JS, Tan M, Zhang M, Liu J, Chen CH, Lee JS, Perry B, Sternberg PW. A cGAL-UAS bipartite expression toolkit for Caenorhabditis elegans sensory neurons. Proc Natl Acad Sci U S A. 2023 Dec 19;120(51):e2221680120. doi: 10.1073/pnas.2221680120. Epub 2023 Dec 14. PMID: 38096407.https://doi.org/10.1073/pnas.2221680120
CO2 and dauer: Banerjee N, Rojas Palato EJ, Shih PY, Sternberg PW, Hallem EA. Distinct neurogenetic mechanisms establish the same chemosensory valence state at different life stages in Caenorhabditis elegans. G3 (Bethesda). 2023 Nov 23:jkad271. doi: 10.1093/g3journal/jkad271. Epub ahead of print. PMID: 38092065.
Banerjee N, Shih PY, Rojas Palato EJ, Sternberg PW, Hallem EA. Differential processing of a chemosensory cue across life stages sharing the same valence state in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2023 May 9;120(19):e2218023120. doi: 10.1073/pnas.2218023120. Epub 2023 May 1. PMID: 37126715; PMCID: PMC10175840.
mating behavior: Weng JW, Park H, Valotteau C, Chen RT, Essmann CL, Pujol N, Sternberg PW, Chen CH. Body stiffness is a mechanical property that facilitates contact-mediated mate recognition in Caenorhabditis elegans. Curr Biol. 2023 Jul 28:S0960-9822(23)00927-2. doi: 10.1016/j.cub.2023.07.020. Epub ahead of print. PMID: 37541249.
Reilly DK, Schwarz EM, Muirhead CS, Robidoux AN, Narayan A, Doma MK, Sternberg PW, Srinivasan J. Transcriptomic profiling of sex-specific olfactory neurons reveals subset-specific receptor expression in Caenorhabditis elegans. Genetics. 2023 Apr 6;223(4):iyad026. doi: 10.1093/genetics/iyad026. PMID: 36801937; PMCID: PMC10319972.
Cell biology: Tan C-H, Chen K-W, Park H, Sternberg PW, Chou T-F. (2023). LINKIN-associated proteins necessary for tissue integrity during collective cell migration. bioRxiv https://doi.org/10.1101/2023.02.02.527750
Alliance preprint: Alliance of Genome Resources Consortium. Updates to the Alliance of Genome Resources Central Infrastructure. bioRxiv [Preprint]. 2023 Nov 22:2023.11.20.567935. doi: 10.1101/2023.11.20.567935. PMID: 38045425; PMCID: PMC10690154.
GO: Gene Ontology Consortium. The Gene Ontology knowledgebase in 2023. Genetics. 2023 May 4;224(1):iyad031. doi: 10.1093/genetics/iyad031. PMID: 36866529; PMCID: PMC10158837.
knowledge modeling: Prakash SJ, Van Auken KM, Hill DP, Sternberg PW. Semantic Representation of Neural Circuit Knowledge in Caenorhabditis elegans. Brain Inf. 10, 30 (2023). doi: 10.1101/2023.04.28.538760. PMID: 37162850; PMCID: PMC10168330.
transcriptomics: Truong L, Chen YW, Barrere-Cain R, Levenson MT, Shuck K, Xiao W, da Veiga Beltrame E, Panter B, Reich E, Sternberg PW, Yang X, Allard P. Single-nucleus resolution mapping of the adult C. elegans and its application to elucidate inter- and trans-generational response to alcohol. Cell Rep. 2023 May 23;42(6):112535. doi: 10.1016/j.celrep.2023.112535. Epub ahead of print. PMID: 37227821.
Imaging: Holman EA, Krishnan H, Holman DR, Holman HN, Sternberg PW. Toward implementing autonomous adaptive data acquisition for scanning hyperspectral imaging of biological systems. Appl Phys Rev. 2023 Mar 28;(10)1:011319.
weird photochemistry artifact analyzed: Chieh-Hsiang Tan, Keke Ding, Mark G Zhang, Paul W. Sternberg. Fluorescence dynamics of lysosomal-related organelle flashing in the intestinal cells of Caenorhabditis elegans. bioRxiv [Preprint]. 2023. doi: https://doi.org/10.1101/2023.10.16.562538
data standards: Wright A, Wilkinson MD, Mungall C, Cain S, Richards S, Sternberg P, Provin E, Jacobs JL, Geib S, Raciti D, Yook K, Stein L, Molik DC. DATA RESOURCES AND ANALYSES FAIR Header Reference genome: A TRUSTworthy standard. bioRxiv [Preprint]. 2023 Dec 1:2023.11.29.569306. doi: 10.1101/2023.11.29.569306. PMID: 38076838; PMCID: PMC10705436.doi: https://doi.org/10.1101/2023.11.29.569306
Rodak, NY; Tan, CH; Sternberg, PW (2024). An improved solid medium-based culturing method for <i>Steinernema hermaphroditum</i>. microPublication Biology. <a href="https://doi.org/10.17912/micropub.biology.001110" target="_blank" rel="noopener noreferrer">10.17912/micropub.biology.001110</a>.