Animal Development, Gene Expression and Locomotion In The Nematode, Caenorhabditis elegans.
Animal development is the process by which a single cell, the fertilised egg, becomes a mature and highly complex adult organism. Differential gene expression from cell to cell is a major factor in the generation of the cellular diversity generated during development. Nerve cells and muscle cells function to drive an animal's interaction with the environment to achieve purposeful locomotion. The nematode worm Caenorhabditis elegans (C. elegans) has many characteristics which make this species a particularly powerful model system for study of various aspects of biology, including development, genetics and behaviour. (See WormClassroom for more background information.) C. elegans is the subject of the research pursued in this laboratory.
Through the years we have used a series of approaches, with progressive improvements in efficiency and quality, for determination of the developmental expression patterns for genes across the C. elegans genome. In each approach regulatory regions of C. elegans genes have been fused to a reporter gene and transgenic C. elegans lines, transformed with these constructions, were examined to reveal gene expression patterns in situ. (See the publications from this laboratory for full details.) The strategies used most recently have involved MultiSite Gateway Recombination and Recombineering. MultiSite Gateway Recombination was applied in a collaboration led by Marc Vidal (CCSB, DFCI, Harvard), and including Marian Walhout (UMass Med School). Transgenic C. elegans lines containing these reporter gene fusions were made by microprojectile bombardment rather than the microinjection procedures used previously (Reece-Hoyes, J.S. et al. ('07) BMC Genomics, 8, 27, Dupuy, D., et al. ('07) Nature Biotechnology, 25, 663-8.). Currently, however, we use recombineering of fosmids to introduce reporter genes seamlessly into precise positions within genes within large genomic DNA fragments to maximize the likelihood that all regulatory elements acting on the target gene have been retained (Dolphin, C.T. and Hope, I.A. ('06) Nucleic Acids Research, 34, e72.) in a collaboration with Colin Dolphin (King's College, London). Recombineering has been used specifically to examine the operon based expression of the C. elegans sirtuin gene sir-2.1 (Bamps, S. et al. ('09) Mech. Aging Development, 130, 762-70.) and the regulation of transcription factor genes expressed in the nervous system (Bamps, S. et al. ('11) Mol. Genetics Genomics, 286, 95-107, Feng, H. et al. ('12) Gene, 494, 73-84.). Results of these studies are contributing to our understanding of how gene expression is orchestrated, genome wide, through development (Craig et al. ('13) BMC Genomics, 14, 249.).
Recently, collaborations with Elwyn Isaac (also in School of Biology, Leeds) and Netta Cohen (School of Computing, Leeds) have led into Systems Biology and Computer Modelling concerning the C. elegans nervous system and locomotory behaviour. For example, the differential turnover of proteins integral to muscle contraction has been documented (Ghosh, S. and Hope, I.A. ('10) Eur. J. Cell Biol. 89, 437-48.) and mathematical representations of C. elegans movement across an agar surface and in liquid of varying viscosities have been derived (Berri, S. et al. ('09) HFSP J., 3, 186-93, Boyle, J. et al. ('11) Frontiers in Behavioral Neuroscience, 5, 10.). Another collaboration, this time with Steve Sait (also in School of Biology, Leeds), has led in an ecological direction. The genetics behind the link between cold tolerance and longevity in C. elegans has been characterized (Savory, F. et al. ('11) PLoS One, 6, e24550.; Savory, F.R. et al ('14) Ecol. Evol., 4, 1176-85.). And yet another collaboration, this one with Marie-Anne Shaw (in the Leeds Institute of Biomedical & Clinical Sciences), is leading to use of C. elegans as a model for human malignant hyperthermia and related conditions.
Follow this link for more publications from this laboratory.
All the expression pattern data we have generated are available in our database. Our data may also be found in the C. elegans database WormBase, where it is integrated with the genetic and sequence data for this organism.
Another major project to determine gene expression patterns in C. elegans using reporter gene fusions, but constructed using an alternative strategy, is underway at UBC. The data generated by the BC C. elegans Gene Expression Consortium can be found on their web site at http://gfpweb.aecom.yu.edu/index. The BC database also includes expression pattern data generated by SAGE.
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