Zhao, Charles L et al. (2013) International Worm Meeting "New Computational Techniques for Automated Mutant Sorting, and an Application to the Identification of Synaptic Mutants in C. elegans."

Zhen, Mei, Zhao, Charles L, Lim, Ria, Lu, Hang

[International Worm Meeting, 2013]

The advent of microfluidics has enabled the development of high-throughput mutant sorting, expediting a previously tedious, manual procedure, and enabling the sorting of tremendous numbers of worms. However, to be effective, automated sorting relies on two layers of computational decision making: feature extraction from detected objects, and mutant identification. In the context of synaptogenesis, we examine new and existing general techniques which improve decision accuracy. With the role of malformed synapses in disease, synaptogenesis has attracted much study, but the need for fluorescent markers and the subtlety of mutant phenotypes have made screening challenging. Pixel-based classification identifies putative varicosities, but misclassifies fat droplets and other similar-looking auto-fluorescent objects. Human observers perform better, relying on the arrangement of varicosities along axons. Using image sets taken from synaptically-labeled strains of C. elegans, we show that density-based clustering can enhance the accuracy of varicosity identification and, hence, feature extraction. When structure is obvious to a human, density-based clustering can refine object classification. This can enable more effective image processing for a variety of applications. We further demonstrate improvements in mutant detection. Multiple thresholding performs well, but may neglect subtle multi-feature mutants. We demonstrate that, with reasonable assumptions, an Independent Component Analysis (ICA) can greatly simplify Parzen outlier detection. The method reliably extracts difficult mutants, achieving higher true positives with similar false positives, while requiring smaller sample sizes than necessary for the full Parzen method. To gain further insight, we compare the performance of our method with SVDD, one-class SVMs, and the full Parzen method.

Miller DM et al. (1992) Worm Breeder's Gazette "unc-4 LacZ Expression in A-Type Motor Neurons"

Miller DM, Niemeyer CJ

[Worm Breeder's Gazette, 1992]

unc-4 LacZ expression in A-type motor neurons David M. Miller and Charles J. Niemeyer, Dept. of Cell Biology, Duke Univ. Medical Ctr, Durham, NC 27710

Zhao C et al. (1993) Worm Breeder's Gazette "Cloning of the lin-32 Gene"

Emmons SW, Zhao C

[Worm Breeder's Gazette, 1993]

Cloning of the lin-32 gene Connie Zhao and Scott W. Emmons, Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461

Opperman CH et al. (1992) Parasitol Today "Nematode acetylcholinesterases--molecular forms and their potential role in nematode behavior."

Chang S-H, Opperman CH

[Parasitol Today, 1992]

Nematode movement is reliant upon the somatic musculature that runs longitudinally along the body wall. Neuromuscular synapses occur in the ventral and dorsal cords and employ the excitatory neurotransmitter, acetylcholine (ACh), for modulation of muscle activity. Acetylcholine activity is terminated by hydrolysis by acetylcholinesterase (AChE). Here, Charles Opperman and Stella Chang discuss the molecular forms and potential role of this enzyme.

Bowerman B et al. (2019) Dev Cell "Breaking Symmetry: Worm Cue Finally Found."

Bowerman B, Sugioka K

[Dev Cell, 2019]

In this issue of Developmental Cell, Zhao etal. (2019) show that the Aurora A kinase AIR-1 is the long-sought cue that downregulates cortical actomyosin to establish anterior-posterior polarity in the C.elegans zygote, diffusing from centrosomes to the overlying cortex to phosphorylate yet to be identified target(s).

Zhao, Yuehui et al. (2015) International Worm Meeting "Multigene analysis of aging markers in Caenorhabditis elegans using directed evolution."

Bates, Kathy, Lu, Hang, Zhao, Charles, Zhao, Yuehui, McGrath, Patrick

[International Worm Meeting, 2015]

Many human traits, including aging, are influenced by genetic variation. Decades of classical genetic screens and molecular biology research have identified several conserved signaling pathways involved in aging process. However, aging and most complex diseases are controlled by the collective actions of multiple genes. Classical genetic methods are biased towards isolating single-large effect gene that unlikely to explain aging mechanism completely. Thus, we may still miss genes with a subtle effect or work in specific genetic backgrounds to influence aging. To further understand the genetic architecture and molecular mechanism of aging, we are developing directed evolution as a new approach to generate and collect multi genetic changes affect aging in the model organism Caenorhabditis elegans. Previous research reports the expression level of a microRNA mir-71 can predict lifespan in young adult animals. We are performing unbiased mutagenesis of a strain with Pmir-71::GFP and sorting the animals with stronger GFP signal by high-throughput microfluidics system. By performing multiple mutagenesis-sorting experiments, genetic mutations have subtle effects or epistasis to influence aging can be accumulated and be rapidly identified by deep sequencing. We believe this approach can result in identifying new genes and new pathways involved in aging and enable us further the understanding of aging genetic network.

Sterling P et al. (2023) Anim Cogn "Why an animal needs a brain."

Sterling P, Laughlin S

[Anim Cogn, 2023]

In Principles of Neural Design (2015, MIT Press), inspired by Charles Darwin, Sterling and Laughlin undertook the unfashionable task of distilling principles from facts in the technique-driven, data-saturated domain of neuroscience. Their starting point for deriving the organizing principles of brains are two brainless single-celled organisms, Escherichia coli and Paramecium, and the 302-neuron brain of the nematode Caenorhabditis elegans. The book is an exemplar in how to connect the dots between simpler and (much) more complex organisms in a particular area. Here, they have generously agreed to republish an abridged version of Chapter 2 (Why an Animal Needs a Brain), in which many of their principles are first described.

Terskikh A et al. (2000) Science ""Fluorescent timer": protein that changes color with time."

Matz M, Ermakova G, Siebert P, Kim SK, Lukyanov S, Kajava AV, Weissman I, Zaraisky A, Terskikh A, Tan PBO, Fradkov A, Zhao X

[Science, 2000]

We generated a mutant of the red fluorescent protein drFP583. The mutant (E5) changes its fluorescence from green to red over time. The rate of color conversion is independent of protein concentration and therefore can be used to trace time-dependent expression. We used in vivo labeling with E5 to measure expression from the heat shock-dependent promoter in Caenorhabditis elegans and from the Otx-2 promoter in developing Xenopus embryos. Thus, E5 is a "fluorescent timer" that can be used to monitor both activation and down-regulation of target promoters on the whole-organism scale.AD - School of Medicine, Stanford University, Stanford, CA 94305, USA. Alexey.Terskikh@Stanford.eduFAU - Terskikh, AAU - Terskikh AFAU - Fradkov, AAU - Fradkov AFAU - Ermakova, GAU - Ermakova GFAU - Zaraisky, AAU - Zaraisky AFAU - Tan, PAU - Tan PFAU - Kajava, A VAU - Kajava AVFAU - Zhao, XAU - Zhao XFAU - Lukyanov, SAU - Lukyanov SFAU - Matz, MAU - Matz MFAU - Kim, SAU - Kim SFAU - Weissman, IAU - Weissman IFAU - Siebert, PAU - Siebert PLA - engID - 1 RO3 TW01362-01/TW/FICPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Heat-Shock Proteins)RN - 0 (Luminescent Proteins)RN - 0 (Nerve Tissue Proteins)RN - 0 (Otx2 protein)RN - 0 (Trans-Activators)RN - 0 (red fluorescent protein)SB - IM

Memar, Nadin et al. (2009) International Worm Meeting "A view on the embryogenesis of the Caenorhabditis Family."

Martin, Katharina, Schnabel, Ralf, Memar, Nadin

[International Worm Meeting, 2009]

The molecular differences of the four Caenorhabditis species C. elegans, C. briggsae, C. remanei and C. brenneri are currently of great interest, however little is known about development. Zhao et al. (2008) reported an automatic lineage of C. briggsae and came - based mostly on the cleavage pattern and cell positions - to the conclusion that the embryogenesis of the two species is very similar. We now present detailed 4D analyses of the species including the terminal differentiation patterns. All analyses including bioinformatical quantifications of cell behaviour show a huge similarity between those species. Immunochemical analyses of the tissue distributions only reveal a difference in the intestinal differentiation of C. brenneri. Interestingly hybrid embryos always appear to fail in different ways in embryogenesis.

Wyatt TD (2017) Curr Biol "Pheromones."

Wyatt TD

[Curr Biol, 2017]

The reality of invisible chemical signals, pheromones, between members of the same species was recognized long before they could be identified. Charles Darwin proposed that the breeding season sexual smells of male crocodiles, goats and other animals, too, could have evolved by sexual selection of the smelliest males through female choice. But it's not just sex. We now know that pheromones are used by species all across the animal kingdom, in every habitat, and in a wide range of biological contexts, from trail, alarm, and queen pheromones in social insects to the mammary pheromone produced by mother rabbits. Pheromones have provided fascinating examples of signal evolution. In some model organisms, such as moths, Drosophila, Caenorhabditis elegans, and Mus musculus, a complete signaling system can be genetically dissected, from the enzymes producing pheromones, perception by chemosensory receptors, through to the neural circuits processing the signals.