The central aim of projects in the McGhee laboratory is to understand, at the molecular level, the development of the intestine in the small free-living nematode worm Caenorhabditis elegans.  The major emphasis is on transcriptional control, i.e. what transcription factors are involved in controlling which genes, and how does it all work?  The following are summaries of the individual projects ongoing during 2009.

·         The year began with the publishing of our study demonstrating that the GATA-type transcription factor ELT-2 is the predominant protein controlling transcription of the large majority (possibly all) of genes expressed in the intestine, beginning at a point when the intestine has only two cells and ending when the worm dies several weeks later.

·         We produced worm strains that are now being used to investigate transcriptional control in the very early embryo (when the endoderm has only one or two cells).  These early embryonic intestine cells will be purified by FACs sorting and complete transcript inventories will be produced.  The aim is to understand how earlier transcription factors hand off control to the ELT-2 factor and to identify the genes involved in the earliest steps of intestinal formation.

·         We spent a large fraction of our efforts working on biochemical methods to test our model for ELT-2 predominance.  These efforts are persisting.  We are also extending this approach into the study of chromatin (e.g. nucleosome phasing) in the developing intestine.

·         We continued our analysis of the elt-2 gene promoter, in order to determine what controls the initiation of elt-2 transcription in the early embryo.

·         We have worked on several projects with the aim of understanding how other intestinal transcription factors combine with ELT-2 in order to confer special properties of transcriptional control on target genes in the intestine.  In particular, we have uncovered a TGF-Beta/SMAD pathway that impinges on the promoter of yolk genes and works in combination with ELT-2.  Our general view is that this dual mechanism of gene control might be how the mother worm assesses the availability of food in her environment and decides whether to continue producing oocytes (“the molecular basis of maternal resource allocation”).

·         An undergraduate-led project in the lab disproved the central observation of a recent high profile paper claiming that the hypodermal GATA factor ELT-3 is centrally involved in the aging-longevity pathway of C. elegans.

·         We have essentially completed a proteomic (mass spectrometry) study of the C. elegans oocyte.

• “Development of the c. elegans intestine” 2007-2012

• “Tier 1 Canada Research Chair in Developmental Biology: 2002-2009