Grant: Operating Grant

The small free-living worm Caenorhabditis elegans has only a thousand cells in its body; its intestine has only twenty cells. In contrast, human intestines have trillions of cells. Yet the worm intestine and our own intestine have many similar features and clearly came from some ancient common ancestor. We have been studying how the worm intestine develops from a single cell to a functioning digestive organ in roughly 12 hours. We have found that the transcription factor that controls most of intestine development (i.e. the particular protein responsible for turning intestine genes on and off) is highly similar to the transcription factor that controls the development of our own intestines. In this proposal, we first wish to ask questions of mechanism, i.e. how does all this work? Secondly, we will isolate an entire active gene from the intestine, together with its chromosomal environment, and then identify all the associated proteins (using the technique known as mass spectrometry). Thirdly, we will being to investigate how intestine genes become active inside the living developing worm embryo, using the newest generation of so-called "super-resolution " microscopes, which can detect single molecules. The hope is that we will begin to understand intestine development at a detail that was thought impossible only a few years ago.