Development of multi-cellular organisms is an ideal model to study the sources contributing to phenotypic variation, such as disease susceptibility, agriculturally or evolutionarily important features. The corollary question, regarding factors that contribute to the robustness of development and phenotypic stability, is however under-appreciated.
The project aims to identify factors that influence the variation and stability of transcription of genes regulating the early development in Drosophila (an unparalleled model species). To this end, several steps will and have been taken. Firstly, population samples show that there is considerable variation in regulatory sequences within D. melanogaster, with several mutations affecting DNA known to be important for expression. The plan is to extend this survey to more genes and survey additional species. Secondly, the focus is on the intrinsic noise in expression, and testing explicitly the novel hypothesis that somatic mutations in the DNA binding domains of Transcription factor proteins contribute. The third component relates to the second, and centres on testing the utility of fruitflies as a model species to study somatic mutations at the DNA level.
A combination of cutting edge population and experimental genetics will be applied to study the stability of development in this unique system. This can identify the factors affecting stability and variation in phenotypes, and by testing the effects of somatic mutations, the study is designed to improve our understanding of the material basis of cancer.
Fields of science
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