Project R-2902

Validation and valorisation of flatworms as model system in primary toxicity screenings (Research)

To determine the toxicity of substances - present in the environment, in food or in drugs- a wide range of screening assays exists. Most of these currently used model systems have a limited repertoire of responses, are expensive to maintain and manipulate and are not suitable for a variety of techniques. This increases the costs and the time that has to be invested in toxicity screenings. In this study, the flatworms Schmidtea mediterranea and Macrostomum lignano are presented as new model organisms for 'first line' toxicity screenings. These organisms are sensitive to low concentrations of external toxins as they rapidly exhibit toxic responses. They show a high degree of similarity with vertebrates concerning anatomical, physiological and biochemical organization, which ensures a similar sensitivity for a lot of toxic compounds. In addition, they have a well-organized nervous system that contains many of the same neuroactive compounds as vertebrates and that enables a broad behavioral repertoire. However, the most exceptional property of both organisms is the presence of a totipotent, somatic stem cell system, consisting of neoblasts, which provides these flatworms an enormous regenerative potential. As neoblasts are the only dividing cells in the adult flatworm, carcinogenic responses in these animals are being dedicated to stem cell responses. In addition, flatworms are inexpensive and easy to maintain in the laboratory, and they are suitable for a variety of techniques (RNAi, transgenesis, stains). In summary, we propose S. mediterranea and M. lignano as suitable organisms for pre-screening toxic substances. This hypothesis will be examined by determining if these organisms expose specific markers of carcinogenicity and neurotoxicity. I will focus on ultrastructural and molecular markers, as our laboratory has built up an extensive expertise within these domains. With this research, we hope to contribute to a cheaper and more efficient toxicity assay, in which it is possible to reveal new aspects in the disease process of cancer.

01 January 2011 - 31 December 2014