This overall goal of our Proposed Center is to use a physics-based approach towards understanding the evolution of cancer resistance. From an experimental point of view, this will be accomplished using the "microhabitat patch" (MHP) technology developed on a microfluidic chip platform at Princeton. This, experimental technique is central to all aspects of our proposal as it allows us to experimentally "tune" parameters which affect cell migration and evolution and then watch the evolution of interacting populations of cells as they move and evolve in space and time. The main focus of this proposed section of our Center is to rapidly extend this technology to mammalian cells (from initial studies in bacteria), and to develop additional capabilities for such MHP's for studying how cancer cells respond to stress. These include 2-dimensional or 3-dimenstional arrays in addition to 1-dimension, the ability to tune the coupling parameters between MHP's and between MHP's and food supplies as a function of time, and to adjust the local temperature as a function of time. We will also develop approaches for extracting cells from chips after evolution experiments for off-chip genomic analysis, and eventually methods for on-chip genomic analysis. Once these technologies and capabilities are invented and developed, they will be transferred to the Princeton Microfluidic Shared Resource (Section N4) so that all Center members (cancer biologists, e.g.) and external researchers such as those on pilot or transnetwork projects can use the new capabilities.
The main focus of this proposed section of our Center is to rapidly extend this technology to mammalian cells (from initial studies in bacteria), and to develop additional capabilities for such MHP's for studying how cancer cells respond to stress.
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