Zarkower D et al. (1994) Worm Breeder's Gazette "mab-3 YAC Rescue"

De Bono M, Hodgkin JA, Zarkower D

[Worm Breeder's Gazette, 1994]

mab-3 YAC rescue David Zarkower, Mario de Bono, and Jonathan Hodgkin MRC Laboratory of Molecular Biology, Cambridge, England

Hu KJ et al. (1999) Nematology "Nematicidal metabolites produced by Photorhabdus luminescens (Enterobacteriaceae), bacterial symbiont of entomopathogenic nematodes."

Hu KJ, Li JX, Webster JM

[Nematology, 1999]

The secondary metabolites, 3,5-dihydroxy-4-isopropylstilbene (ST) and indole, from the culture filtrate of Photorhabdus luminescens MD, were shown to have nematicidal properties. ST caused nearly 100% mortality of 54 and adults of Aphelenchoides rhytium, Bursaphelenchus spp. and Caenorhabditis elegans at 100 mu g/ml, but had no effect on J2 of Meloidogyne incognita or infective juveniles (IJ) of Heterorhabditis megidis at 200 mu g/ml. Indole was lethal to several nematode species at 300 mu g/ml, and caused a high percentage of Bursaphelenchus spp. (54 and adults), M, incognita (J2) and Heterorhabditis spp. (IJ) to be paralysed at 300, 100 and 400 mu g/ml, respectively. Both ST and indole inhibited egg hatch of M, incognita. ST repelled IJ of some Steinernema spp. but not IJ of Heterorhabditis spp., and indole repelled IJ of some species of both Steinernema and Heterorhabditis. ST, but not indole, was produced in nematode-infected larval Galleria mellonella. after 24 h infection.

Melentijevic, Ilija et al. (2021) International Worm Meeting "High Throughput Exopher Whole Genome RNAi Screening with Machine Vision and Machine Learning Approaches"

St. Ange, Jonathan, Abbott, Mark, Guasp, Ryan, Driscoll, Monica, Melentijevic, Ilija

[International Worm Meeting, 2021]

It has recently come to be appreciated that neurodegenerative disease proteins/aggregates can be found outside of mammalian neurons, and when outside can actually be taken up by neighboring cells. Transfer of offending molecules has been suggested to be a mechanism of pathogenesis spread for multiple neurodegenerative diseases, including the prevalent Alzheimer's and Parkinson diseases. We discovered a novel capacity of young adult C. elegans neurons to extrude substantial membrane-bound packages of cellular contents via exohers, which can include aggregated human neurodegenerative disease proteins, mitochondria, or lysosomes, but no nuclear DNA. We speculate that the mechanism of exopher formation in C. elegans is analogous to that used in the transfer of aggregated proteins in human neurodegenerative disease. If so, it will be absolutely critical for us to identify genes contributing to the recognition/sorting of cellular trash and to the expulsion of this material. Although we have identified some exopher mechanism players in candidate gene RNAi screens, measurement rates are slow and important players are likely hard to predict, necessitating an unbiased candidate approach and faster methods in order to elucidate a genetic mechanism. To accomplish genome-wide screens for exopher-genesis modifier genes, we have developed a highly automated, high-throughput whole-genome RNAi screening platform that can be implemented at a fraction of the time and cost of manual screens. Our screening protocol employs robotic dispensers and aspirators, coupled with a high content imaging system for animals grown and measured in a 96-well plate format that mimics a standard solid media plate environment. We are developing several machine vision approaches to allow for automated scoring of animals with an exopher to expedite the analysis. Our screen protocol allows for an entire genome to be screened in about two weeks, fast enough to allow for replicated screens and epistasis analysis of hits. We have developed approaches to store a 3D digital library and physical library of prepared samples for later re-imaging at higher resolution and re-analysis. We will present our current genetic approaches to establish a high exopher baseline, and computational approaches to detect exopher events in a crowded well.

Hresko MC et al. (1994) Worm Breeder's Gazette "Shoot First, Ask Questions Later"

Shrimankar PV, Hresko MC, Waterston RH

[Worm Breeder's Gazette, 1994]

Shoot First, Ask Questions Later M.C Hresko, P.V. Shrimankar and R.H. Waterston. Washington Univ. Sch. of Med., St. Louis, MO 63110. coutu@sequencer.wustl.edu and pvs@elegans.wustl.edu

McCarter JP et al. (1994) Worm Breeder's Gazette "Somatic Regulation of Germ-line Development. Introduction and Part I; Mitotic Proliferation"

Schedl TB, McCarter JP

[Worm Breeder's Gazette, 1994]

Somatic Regulation of Germ-line Development Introduction, and Part I; Mitotic Proliferation Jim McCarter and Tim Schedl. Dept. of Genetics, Washington Univ. School of Medicine, St. Louis, MO 63110, jim@wugenmail.wustl.edu

Melentijevic, Ilija et al. (2019) International Worm Meeting "Exophers colocalize with hypodermal lysosomes via endocytic trafficking."

Melentijevic, Ilija, St. Ange, Jonathan, Grant, Barth, Wang, Yu, Parekh, Manan, Driscoll, Monica

[International Worm Meeting, 2019]

A general hallmark of neurodegenerative disease is pathology associated with aberrant aggregates. Moreover, it has recently come to be appreciated that neurodegenerative disease proteins/aggregates can be found outside of mammalian neurons, and when outside can actually be taken up by neighboring cells. Transfer of offending molecules has been suggested to be a mechanism of pathogenesis spread for multiple neurodegenerative diseases, including the prevalent Alzheimer's and Parkinson diseases. Understanding of the basic mechanisms by which aggregates are extruded and handled by their cellular neighbors is thus a critical problem is neurodegenerative disease. We discovered a novel capacity of young adult C. elegans neurons to extrude large membrane-bound packets of cellular contents called exohers, which can include aggregated human neurodegenerative disease proteins, mitochondria, or lysosomes, but no nuclear DNA. Interestingly, exophers can selectively incorporate aggregation-prone proteins and oxidized mitochondria. Exophers extruded from touch neurons are initially taken up by the hypodermis, after which their fluorescent contents are either degraded, persist in a networked form we have called the "starry night" phenotype, or are thrown about again into the pseudocoloem and appear later in remote cells. The extruded exopher clearance in the hypodermis appears to be mediated by the ced-1, ced-6, and ced-7engulfment pathway, but how exopher content is handled by the hypodermis is unknown. We have begun to track the molecular details by which the hypodermis addresses invading exopher contents. Our investigations into the hypodermal processing of exopher mCherry aggregates shows that the aggregates will colocalize with the hypodermal lysosome network, as visualized by the lysosome membrane protein SCAV-3::GFP. We also find that this touch neuron-derived cargo colocalizes with late endosome components RAB-7 and RAB-10. We will present these findings as well as current data on other phagocytosis, endocytosis and autophagic machinery that influence our working models of the fates of extruded cargoes derived from neurons that end up in other cells.

Consortium TCeGS (1994) Worm Breeder's Gazette "The C. elegans Genome Sequencing Project: A Progress Report."

Consortium TCeGS

[Worm Breeder's Gazette, 1994]

The C. elegans genome sequencing project: A progress report. The C. elegans Genome Consortium, Genome Sequencing Center, Washington University School of Medicine, St. Louis, Missouri, USA and Sanger Centre, Hinxton Hall, Cambridge, UK.

Consortium TCeGS (1994) Worm Breeder's Gazette "The C. elegans Genome Sequencing Project: A Progress Report"

Consortium TCeGS

[Worm Breeder's Gazette, 1994]

The C. elegans genome sequencing project: A progress report. The C. elegans Genome Consortium, Genome Sequencing Center, Washington University School of Medicine, St. Louis, Missouri, USA and Sanger Centre, Hinxton Hall, Cambridge, UK.

Li WQ et al. (1992) Worm Breeder's Gazette "Characterization of the Axonal Guidance and Outgrowth gene Unc-33"

Shaw JE, Li WQ, Herman RK

[Worm Breeder's Gazette, 1992]

Characterization of the axonal guidance and outgrowth gene unc-33 W. Li, R. K. Herman and J. E. Shaw Department of Genetics and Cell biology, University of Minnesota, St Paul, MN 55108

Verma S et al. (2015) IUBMB Life "Understanding the complexities of Salmonella-host crosstalk as revealed by in vivo model organisms."

Srikanth CV, Verma S

[IUBMB Life, 2015]

Foodborne infections caused by non-typhoidal Salmonellae, such as Salmonella enterica serovar Typhimurium (ST), pose a major challenge in the developed and developing world. With constant rise of drug-resistant strains, understanding the epidemiology, microbiology, pathogenesis and host-pathogen interactions biology is a mandatory requirement to enable health systems to be ready to combat these illnesses. Patient data from hospitals, at least from some parts of the world, have aided in epidemiological understanding of ST-mediated disease. Most of the other aspects connected to Salmonella-host crosstalk have come from model systems that offer convenience, genetic tractability and low maintenance costs that make them extremely valuable tools. Complex model systems such as the bovine model have helped in understanding key virulence factors needed for infection. Simple systems such as fruit flies and Caenorhabditis elegans have aided in identification of novel virulence factors, host pathways and mechanistic details of interactions. Some of the path-breaking concepts of the field have come from mice model of ST colitis, which allows genetic manipulations as well as high degree of similarity to human counterpart. Together, they are invaluable for correlating in vitro findings of ST-induced disease progression in vivo. The current review is a compilation of various advances of ST-host interactions at cellular and molecular levels that has come from investigations involving model organisms.