Research and Technology Programs

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To address the question of how the specific size and shape of the Drosophila wing develops we propose to establish six interdisciplinary and interconnected Research and Technology Programs (RTP).

• In vitro culture system for imaginal discs: Using state-of-the-art microengineering technologies we will develop micro-culture chambers for the long term culture of imaginal discs. This system will not only permit imaging of wing development over extended periods of time but it will also facilitate high resolution measurements and perturbation studies using physical, chemical, and genetic tools. This system will also be used to assemble wing discs de novo from embryonic precursor cells.

• Development and application of novel imaging techniques: Advanced imaging techniques can provide quantitative information on the expression of genes and the spatiotemporal activity of proteins. A number of imaging techniques (including self focusing through time reversal and X-ray tomography) will be developed. These techniques will enable a 3D reconstruction of wing development from the embryonic progenitor cells to the morphogenesis during pupal stages. Furthermore, the development of an array of dynamic cellular sensors for key signaling pathways involved in growth and patterning will generate real time readouts to assay the response to mechanical, chemical, or genetic perturbations.

• Development and implementation of computational models with predictive capabilities for the development of the Drosophila wing. This project entails the integration of available biological knowledge and experimental data with reverse engineering techniques, advanced image processing algorithms, and uncertainty quantification methods in order to construct effective models for multiscale simulations of wing development. The project relies on combining computations and experiments for the validation of the simulations and further guidance of the experiments in a synergetic approach.

• Implementation of state-of-the-art proteomics tools to characterize the proteome of the developing wing, to quantify essential key signaling components and to determine their spatio- temporal variation in response to genetic perturbations.

• Record temporal and spatial changes in the epigenome during the development of the wing by using novel chromosome immunoprecipitation (ChIP) and deep sequencing methods.

• Establish open-source database tools to facilitate the incorporation of the diverse datasets from this project and to integrate these experimental and computational data with the existing data on wing development including an electronic curation of the information in the published literature.