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See the 2004 C. elegans Knockout Project Midwest Meeting Poster

The C. elegans Gene Knockout Project at OMRF would like to thank the Donald W. Reynolds Foundation for providing the funding for our new home!

The C. elegans Gene Knockout project was initiated in 1998 at OMRF by Dr. Robert Barstead and Gary Moulder as a genomic resource project in support of research programs internationally, using the model organism Ceanorhabditis elegans as a research tool.

C. elegans Lab OMRF
The C. elegans Knockout Lab at OMRF
From Left to Right: Top- Bob Barstead, Gary Moulder, Jeff Holmes, James Robertson
Bottom: Bethany Hannafon, Julia Buckner, Beth Rogers, Julie Farley

The lab itself primarily functions as a production facility, with each bay functioning as a specific station in the production flow.

Library Production
Mutant Library Preparation
Library Screening Organization
Organization of Library Screening

Robotics
Robotics technology helps maintain high-throughput work flow

Library PCR Screening
Investingating New Data Recording Technologies

PCR Results
PCR Results assayed by electrophoresis

Library PCR Screening
Even More PCR Results assayed by electrophoresis

worm picking
Worm Culturing and PCR for mutant isolation

Library PCR Screening
More Isolation of Worm Cultures

C. elegans has become a premier research tool both for basic research and drug discovery. Many pharmaceutical research companies are using C. elegans as a tool to discover and evaluate drugs that may have an impact on human disease.

EleGene is an innovative biotech company focusing on the identification and validation of new drug targets to define lead compounds for the development of novel therapeutic drugs. Founded in February 1999, EleGene operates in the field of neurological disorders as well as in cancer, musculoskeletal disorders and cardiovascular diseases. EleGene´s research strategy is based on the latest technologies in molecular genetics. It exploits the exponentially growing informational background of how homologous genes interact in evolutionary conserved pathways. The central core of our technology platform is the nematode Caenorhabditis elegans, currently the best studied animal model in the world. It stands out among all model organisms due to an entirely sequenced genome, detailed knowledge of its anatomy, and of the connectivity of its nervous system. EleGene is convinced that its C. elegans in vivo system provides a significant improvement over traditional screening procedures. EleGene develops proprietary disease models in less time than it is standard for any other in vivo model. Our "living test tube"-system allows unique high-throughput screening (HTS) of whole animals and will, therefore, accelerate the identification of lead compounds for novel drugs.

Axys Pharmacueticals: Axys' NemaPharm technologies focus exclusively on the use of model animals, principally the well-studied nematode Caenorhabditis elegans (C. elegans), to promote human drug discovery. Most human disease-related genes have structural and functional homologs in simpler model organisms. C. elegans is the most thoroughly understood animal in terms of cellular development, anatomy, and genome content. C. elegans genetic studies have led to major advances in the understanding of several disease pathways.

Devgen: In C. elegans, chemistry and pharmacology can be combined with the power of genetics and molecular biology. Moreover, C. elegans can be grown and genetically manipulated with the speed and ease of a microorganism. Devgen's success in this disease area is based on the fact that insulin signaling is conserved between C. elegans and humans. An insulin-resistant assayable phenotype in C. elegans has been built as model for human type II diabetes (US patent granted in 2001). In summary, the conservation of many aspects of neuronal function between C. elegans and mammals, combined with the versatility of C. elegans for experimental use, makes it a perfect model organism to investigate the biochemical and biological function of complex neuronal and neuromuscular targets.

Collaborations developed during the early phase of our method development have resulted in the publication of a significant body of work clearly demonstrating the value of this work in advancing science both at OMRF and abroad.

 

 

Hao JC, Yu TW, Fujisawa K, Culotti JG, Gengyo-Ando K, Mitani S, Moulder G, Barstead R, Tessier-Lavigne M, Bargmann CI.

C. elegans slit acts in midline, dorsal-ventral, and anterior-posterior guidance via the SAX-3/Robo receptor.
Neuron. 2001 Oct 11;32(1):25-38.
PMID: 11604136 [PubMed - indexed for MEDLINE]

Kelleher JF, Mandell MA, Moulder G, Hill KL, L'Hernault SW, Barstead R, Titus MA.

 

Myosin VI is required for asymmetric segregation of cellular components during C. elegans spermatogenesis.
Curr Biol. 2000 Nov 30;10(23):1489-96.
PMID: 11114515 [PubMed - indexed for MEDLINE]

 

Kohn RE, Duerr JS, McManus JR, Duke A, Rakow TL, Maruyama H, Moulder G, Maruyama IN, Barstead RJ, Rand JB.

Expression of multiple UNC-13 proteins in the Caenorhabditis elegans nervous system.
Mol Biol Cell. 2000 Oct;11(10):3441-52.
PMID: 11029047 [PubMed - indexed for MEDLINE]

 

Friedman L, Higgin JJ, Moulder G, Barstead R, Raines RT, Kimble J.

Prolyl 4-hydroxylase is required for viability and morphogenesis in Caenorhabditis elegans.
Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4736-41.
PMID: 10781079 [PubMed - indexed for MEDLINE]

 

Kraemer B, Crittenden S, Gallegos M, Moulder G, Barstead R, Kimble J, Wickens M.

NANOS-3 and FBF proteins physically interact to control the sperm-oocyte switch in Caenorhabditis elegans.
Curr Biol. 1999 Sep 23;9(18):1009-18.
PMID: 10508609 [PubMed - indexed for MEDLINE]

 

Dernburg AF, McDonald K, Moulder G, Barstead R, Dresser M, Villeneuve AM.

Meiotic recombination in C. elegans initiates by a conserved mechanism and is dispensable for homologous chromosome synapsis.
Cell. 1998 Aug 7;94(3):387-98.
PMID: 9708740 [PubMed - indexed for MEDLINE]

 

Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR, Mukherji M, Metzen E, Wilson MI, Dhanda A, Tian YM, Masson N, Hamilton DL, Jaakkola P, Barstead R, Hodgkin J, Maxwell PH, Pugh CW, Schofield CJ, Ratcliffe PJ.

C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation.
Cell. 2001 Oct 5;107(1):43-54.
PMID: 11595184 [PubMed - indexed for MEDLINE]

 

A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans

 

Sarah L. Crittenden, David S. Bernstein, Jennifer L. Bachorik, Beth E. Thompson, Maria Gallegos, Andrei G. Petcherski, Gary Moulder, Robert Barstead, Marvin Wickens, Judith Kimble
SUMMARY: Germline stem cells are defined by their unique ability to generate more of themselves as well as differentiated gametes. The molecular mechanisms controlling the...

Nature advance online publication DOI: 10.1038/nature754 Letters to Nature

 

 

A new and novel screening technique has been published based on a concept proposed by Gary Moulder at OMRF and a protocol developed by Mark Edgley at UBC Vancouver, BC as part of a joint effort to developed new mutation identification and isolation technologies.

Nucleic Acids Research
VOLUME 30 ISSUE 12
Improved detection of small deletions in complex pools of DNA
Mark Edgley, Anil D'Souza, Gary Moulder, Sheldon McKay, Bin Shen, Erin Gilchrist, Donald Moerman and Robert Barstead

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