The objective of this project is to quantify the genetic program that governs the growth and shape of an organ, namely the Drosophila wing. Using advances in developmental genetics that provide us today with the toolkit (morphogens, transcription factors etc.) of organogenesis, we will employ a synergetic experimental and computational approach to identify how this toolkit is used to build the Drosophila wing of reproducible size and form. We will provide a quantitative description of wing development at a multiscale systems level as determined by the interaction of processes at the molecular, cellular, and tissue level. We consider that the Drosophila wing is a model uniquely suited for a systems biology approach.

In addition, the methods and results of this program will advance the state of the art in developmental biology as spatiotemporal events will be identified at a level of description heretofore impossible. The wing of Drosophila melanogaster is one of the best-studied organ systems. It is a relatively simple system and fundamentally amenable to a systems approach as it originates from a group of progenitor cells set aside during embryogenesis, that develop as a single-layer epithelium composed of ultimately some 60'000 cells. Decades of developmental (regeneration, transdetermination), cell biological (imaging, mass isolation), and above all genetic research (clonal analysis, signaling pathways) provide a solid foundation for a systems approach.

Despite the vast progress, some of these hitherto very successful approaches have reached their limits. The potential of genetic screens to identify key regulators has been almost fully exploited. The transition to a systems level understanding requires new approaches involving expertise and technical developments that cannot come from the presently strong biology community alone. Specifically, there is a need for in vitro culture systems, imaging techniques and systematic modeling efforts as well as higher sensitivity genomics and proteomics tools.

This project is inherently interdisciplinary and will provide a fertile ground for the interaction among different experimental and computationally oriented groups. We aim to exploit this interdisciplinarity to form a new generation of scientists capable of transcending disciplines while conducting state of the art research in systems biology. To this effect we envision projects conducted by pairs of graduate students from different disciplines working jointly under the supervision of two group leaders. Since systems biology research requires a different kind of biology and physics education the project also includes a training program for students (MSc and PhD) of the associated groups.

Developing Drosophila wing is a substantially more challenging system for a systems approach than cellular or subcellular systems to which this new type of scientific approach is successfully applied presently. However, the Drosophila wing is well suited as a model multicellular tissue for such an approach because of its relative simplicity and the high degree of biological understanding. The results obtained will advance the understanding of organogenesis and will set new standards in the application of optical and computational methods for complex biological problems.