An ordinary nematode that has a great deal in common genetically with humans will improve our insight into the development of cancer. A group of European scientists led by Jan Kammenga of the Laboratory for Nematology at Wageningen University is exploring the genetic variation of the Caenorhabditis elegans and the development of its genitalia.
The C. elegans has a length of less than a millimetre and can be found in garden compost heaps. Scientists have been using it as a model organism for many years because it feeds on bacteria, reproduces at a fast pace and is transparent, allowing changes to be easily monitored. The best thing about the C. elegans and its circa 18,000 genes is that it is an 80 percent genetic match for humans and our 22 thousand genes, and therefore easy to manipulate genetically. It has been a rewarding model organism for people in various ways, including research into neurological illnesses such as Alzheimer’s as well as the effects of medications.
System biologists, computer scientists and nematode experts recently joined forces for the first time to see if genetic variation in the C. elegans can be used to predict cancer development in humans, explains Jan Kammenga, coordinator of the project that was given the name Panacea (quantitative pathway analysis of natural variation in complex disease signalling in C. elegans). “People have all different kinds of genotypes: They have the same genes but with slightly different markers. All those different markers can have a different effect on the disease process. We know that genes are involved in cancer but not why some are and some aren’t.” Current research into cancer development mainly consists of association studies examining statistical links between the genes of individuals. Although the results of Panacea are yet to be translated into the human situation, the scientists expect that the research will provide useful clues. The European Union also recognises the potential and has funded the proposal within the Seventh Framework Programme (FP7), the subsidy programme for research and technology development.
The scientists are studying the nematode’s genes that are involved in the development of the body and genitalia. Of those genes, several are identical to the genes responsible for cancer development in humans. “This is what makes the nematode so useful,” says Kamminga. “We know that genitalia start developing differently when certain genes of the C. elegans are over-activated. Now we want to specifically search for candidate genes that are involved in that process.”
In addition to finding new candidate genes responsible for the initial stages of cancer, the scientists are addressing the question of whether the basic processes responsible for cancer development in humans can be modelled. This would be useful for predicting how this development occurs. “If we understand what is happening in the genitalia of the C.elegans and how they are affected by genetic variation, this information can be used to see how it works in humans,” Kamminga adds. Once you have a model you can start predicting, so eventually the step from gene to nematode should become clear. “This synthesis of system biology and genetic variation is what is new in this project, made possible by the new technologies and the resulting data. The challenge is to use this information to make a model.” Kammenga emphasises that his work is not aimed at any specific type of cancer: “The more we know about the basic processes in the nematode, the easier it will be to find out how cancer develops in humans.”
The scientists have already determined the genetic variation within C. elegans and selected the two types with the greatest genetic differences. These have been cross bred and their 200 offspring are now available and characterised. Kammenga: “We are currently measuring the gene transcription in the gene chains, studying protein patterns and monitoring how cell structures can be traced back to genotypes.”
While the C. elegans itself cannot develop cancer, there could be changes in development patterns according to Kammenga. “This means it will look different, for instance with multiple genitalia.”
* Panacea is:
Quantitative pathway analysis of natural variation in complex disease signaling in C. elegans
Source: Yvonne de Hilster, Newsletter Plant Sciences Group, June 2009