James D. McGhee
Professor, Departments of Biochemistry and Molecular Biology Department of Medical Genetics
University of Calgary, Faculty of Medicine
Health Sciences Centre, Room 2205
3330 Hospital Drive NW
Calgary, AB T2N 4N1
Phone: 403-220-4476 Fax: 403-270-0737
Email: jmcghee@ucalgary.ca
Research Interests
Over the past year, we have re-investigated the proposed role for two small GATA-type transcription factors (the med genes) in specifying the C. elegans intestine and have found that their importance has been vastly over-emphasized, at least in part because of mis-interpretation of RNAi experiments. In fact, we find that the med genes play only a small role in allowing intestine genes to be expressed and this finding leads to a re-interpretation of the standard model of endoderm specification in the worm. (published as Captan et al.epub in 2006, final publication February 2007)
• Probably the most important accomplishment over the last year was to assemble a comprehensive list of all genes expressed in the adult C. elegans intestine, revealing the enormous variety of biochemical reactions that the worm uses for digestion and food storage. We have also showed (or made the case) that all of these genes may be controlled by a single master regulator, the ELT-2 transcription factor. The evidence is based on computational analysis of intestinal gene promoters and the approach sets the stage for future quantitative analysis of intestinal gene regulation. (published as McGhee et al epub 2006; final publication February 2007.)
• What began as a short project for a HYRS summer student turned out to have interesting implications for digestion in worms and in ourselves. It can be estimated that an adult C. elegans worm must consume on the order of several million bacteria every day. We showed that the average residence time of each bacterium in the worm intestine was only 1-2 minutes, an incredibly brief period in which to extract nutrients and pointing to the prodigious digestive capacity of the worm. (published as Ghafouri and McGhee, 2007
The above describes completed studies. By far my greatest effort over the past year has been to continue our global analysis of transcriptional control in the C. elegans intestine, from the early embryo to adulthood and all stages in between.) We began with a worm strain in which embryonic intestine cells are labelled with GFP under control of the elt-2 promoter and (in a collaboration) isolated embryonic intestine cells using FACS. I have spent the majority of my time analyzing the SAGE library that we have prepared from these isolated embryonic intestine cells. I am also analyzing the transcript inventory in worms that lack the major transcription factor ELT-2. This latter study is our first to take advantage of the new massively parallel sequencing technologies (again in a collaboration). Overall, our analysis should be (I believe) the most complete analysis of the roles of a single transcription factor driving differentiation of a simple organ, the C. elegans intestine.
Publications
Captan VV, Goszczynski B, McGhee JD. Neither maternal nor zygotic med-1/med-2 genes play a major role in specifying the Caenorhabditis elegans endoderm.
Genetics. 2007 Feb;175(2):969-74. Epub 2006 Dec 6.
McGhee JD, Sleumer MC, Bilenky M, Wong K, McKay SJ, Goszczynski B, Tian H, Krich ND, Khattra J, Holt RA, Baillie DL, Kohara Y, Marra MA, Jones SJ, Moerman DG, Robertson AG. The ELT-2 GATA-factor and the global regulation of transcription in the C. elegans intestine. Dev Biol. 2007 Feb 15;302(2):627-45. Epub 2006 Oct 21.
Ghafouri, S. and McGhee, J.D. (2007) Bacterial Residence Time in the Intestine of Caenorhabditis elegans. Nematology 9: 87-91.
McGhee, J.D. The C. elegans Intestine (March27, 2007) WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.133.1, http://www.wormbook.org
Research Funding
CIHR
CRC
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