The specific objective of this proposal is to take fluorescent imaging instrumentation developed for our shuttle and ISS experiments and calibrate the hardware and data collection capabilities to timeframes optimal for parabolic flight and suborbital applications. We will build on extensive insights gained from spaceflight and ISS deployments of similar technologies, along with PI experience on previous parabolic flight campaigns, to address future science and technology deployments in parabolic and suborbital campaigns. This proposal has longer term development potential for small satellite and planetary lander applications as well, and speaks directly to aspects of the Nanotechnology Road Map (Technology Area 10), particularly the development sensitive, next-generation imagers that can collect data telemetrically, and in real time. This proposal contributes to the programmatic goal of our laboratory, which is dedicated to advancing and defining the technical limits of fluorescence biology telemetry imaging, and to raise that technology toward a readiness for deployment in any of a number of opportunities. Although the focus of this proposal is on applications to parabolic and suborbital flight platforms, insights gained here will support future applications and opportunities, including ASTID proposals, future Human Tended Suborbital calls and SALMON missions such as providing a next-generation instrument for science return from GeneSat and other related satellite missions, as well as future parabolic opportunities dedicated to science. This proposal builds on current shuttle and ISS technology, technology that has yet to be vetted for the parabolic or suborbital realms. The technology is fluorescent imaging of gene expression. The technology is flight ready for experiments involving timeframes reachable on the shuttle and ISS. The technology is not proven to be sensitive or robust enough for experiments involving timeframes reachable on parabolic or suborbital flights. This proposal is distinguished by the unique crosscutting of vetted, ISS spaceflight hardware into the parabolic and then suborbital realms. The instrumentation technology consists of the specialized imaging system, the GFP Imaging System (GIS) imager, a version of which has been operating on the ISS over several increments collecting fluorescence gene expression data. The GIS gathers biological fluorescent data from organisms equipped with a variety of genes designed to report the environmental responses. Data can be collected continuously, autonomously and transmitted telemetrically, making the instrumentation concept applicable for many development routes. In particular, we have strong biochemical evidence for rapid gene responses within parabolic flight parameters , responses that are very different from those seen after days on orbit. This leaves a large gap in knowledge regarding the early stages of spaceflight adaptation, and there is currently no means of collecting biologically relevant data in that timeframe. The anticipated outcome of this proposal is the advancement of the TRL of the GIS imaging system to create a stand-alone, mission -autonomous technology that is monitored solely by telemetry. The biology in this proposal should be viewed primarily as tools of calibration; our technical and operational aims for this flight are to use the parabolic platform to calibrate imager performance with biological responses, and to identify the development path for future deployment. However the need for the development and calibration of this hardware is indeed driven by our, and the scientific community’s hypothesis that there is a series of signal transduction events in biology, which includes human biology, that progress from the onset of a flight environment through an acclimation phase that leads to spaceflight adaptation.