development

how the worm allows humans to investigate themselves

why look at development?

Despite having been completed in 1998, the entire C.elegans genome continues to be a main source of research. Though the sequence is known in its entirety, gene function remains a very ellusive enterprise. Thus, much research is devoted to uncovering each genes' function and its associated pathways with other genes. In turn, due to a high degree of homology with humans, we will be able to use this information to look at our own genes and related biochemical pathways. A key to unlocking "normal" development processes as well as shedding light on "abnormal" development - often referred to as diseased states. To view normal C.elegans development from a single cell to its multi-cell state, click the picture on the right. (*note:you need Quicktime to view the movies which are courtesy of the Goldstein Lab. Upload may take a few minutes).

some techniques used in development research

Along with the invaluable development of many databases, such as those mentioned above, the completion of the C.elegans genome has allowed for the advancement of the DNA microarray which in turn has allowed for a fast search of genomic interactions. Also developed recently, largely due to genomic endeavors, is the ChIP (chromatin immunoprecipitation), which is a technique used prior to the microarray in order to separate your protein or other molecule of choice. A very recently developed tool used in genomic research is that of the gene expression map, developed in the Kim lab at Stanford University. Though this list is far from exhaustive, the last major technique named here is that of worm microinjection which allows a sample of foreign DNA to be integrated into the worm's own DNA with relative ease (Goldstein, 2002). For a further search of other techniques, please go to the other worm links page.

research in development

As stated above, research in C.elegans development is tantamount to understanding our own body's functions, especially at the molecular level. The graph below demonstrates this clearly, showing that humans share nearly all of the worm's essential gene families. Also, the evolution from worm to simple vertebrate to complex vertebrate (fish or human), required only one independent genome duplication.

"Essentially all genes and pathways shown to be important in cell-, developmental- and disease-biology have been found to be conserved between worm and man. This conservation applies to the number and type of protein families, gene structure, the hierarchy of genes in genetic pathways and even gene regulation.

A consequence of this conservation is that human genes can readily be inserted into the worm genome, to functionally replace the worm genes even in complex cell biological and signal transduction pathways. Conversely, key worm genes identified using genetics can be used to trigger specific biochemical processes in human cells."

*(Graph and quote taken by permission from the Devgene website cited below)

Research in development is currently focused on using genomic information to create experiments which identify differential gene expression. In specific cases, this will allow for an understanding of biological pathways at the protein, and thus molecular, level. Determining which genes are active at the same time within an organism's development as well as which genes or their products interact with each other during simultaneous expression is key to piecing together the many biological puzzles.

Some examples of such research include :
(a) use of full-genome DNA microarrays to determine gene expression levels throughout development (Jiang et al.,2001).
(b) use of hundreds of microarrays to develop a new tool for the mapping of gene expression patterns (Kim et al., 2001).
(c) examination of protein interaction via traditional two-yeast hybridizations using the C.elegans genome as guidence (Walhout et al.,2000).

references
1. Jiang, M., Jubin, R., Kiraly, M., Duke, K., Reinke, V., and Kim, S.K. 2001. Genome-wide analysis of developmental and sex-regulated gene expression profiles in Caenorhabditis elegans. Proceedings of the National Academy of Science of the United States of America 98(1):218-223.

2. Kim, S.K., Lund, J., Kiraly, M., Duke, K., Jiang, M., Stuart, J.M., Eizinger, A., Wylie, B.N., and Davidson, G. 2001. A gene expression map for Caenorhabditis elegans. Science 293(5537): 2087-2092.

3. Reinke, V., Smith, H.E., Nance, J., Wang, J., Van Doren, C., Begley, R., Jones, S.J.M., Davis, E.B., Scherer, S., Ward, S., and Kim, S.K. 2000. A global profile of germline gene expression in C. elegans. Molecular Cell 6:605-616

4. Walhout, A.J.M., Sordella, R., Lu, X., Hartley, J.L., Temple, G.F., Brasch, M.A., Thierry-Mieg, N., and Vidal, M. 2000. Protein interaction mapping in C. elegans using proteins involved in vulval development. Science 287(5450):116-122

5. Moving worm, worm development picture and graph courtesy of Devgen found at : http://www.devgen.com/devpage/productoffering/c_elegans.html#top

6. Link to movies courtesy of Dr. Bob Goldstein and the Goldstein lab found at : http://www.bio.unc.edu/faculty/goldstein/lab/