Advanced Screening and Integrative Analysis for Biotechnology and Disease

In the era of big data, there is an ever-increasing breadth of both open-source data and advanced quantitative tools available for studying biology; from RNA-sequencing to high-throughput screening (HTS), advanced technologies have changed the landscape of biological research and medicine. However, there are still many challenges associated with fully harnessing the available resources for particular applications; specifically, comparatively little has been done to integrate data and disparate tools for systems-level solutions. The work herein describes multiple case studies where integrative approaches were applied to synthesize and build on the wealth of resources available to advance biotechnology, preclinical medicine, and more fundamentally in developmental biology. This thesis describes several milestone applications that advance the state-of-the art in each field: the generation of the first chemically defined cell culture medium enabling long term culture of a Drosophila cell lines (Chapter 2); building on these results led to unexpected discoveries in the field of developmental biology with the discovery of novel spatiotemporal patterning of polyamines during organogenesis (Chapter 3); the optimization and application of an in vivo tumor screening approach to efficiently identify novel functional targets during secondary metastatic outgrowth in tumors (Chapter 4); and through a close, multidisciplinary collaboration, the characterization of novel compounds through both cytotoxicity and mechanism of action studies, along with the preliminary creation of an ultra-high-content screening platform for structure-activity analysis of compound libraries (Chapter 5). For each application, several avenues are available to further progress the technology, which is discussed in the concluding chapter (Chapter 6).