Tools and Technologies I
Statement of Benefit to California:
This application focuses on the development of an adaptive optic, wide-field microscope that can be used to image cells deep within living tissues in real time. To achieve these ends, the applicants propose to use techniques conventionally employed by astronomers to quantify and correct optical aberrations caused by imaging through tissues. First, a number of fluorescent beads will be embedded at defined locations within a tissue and serve as reference beacons for quantifying the magnitude of aberration as a function of depth. Next, a microscope will be designed with sufficient correction to adjust and compensate for these measured aberrations. Finally, after building and testing its performance, the applicants propose to use this new microscope to examine mechanisms of stem cell self-renewal in a Dropsophila model system. The reviewers were enthusiastic about the proposed technology and its potential to advance stem cell science. The proposal was straightforward, well written and based on a sound and innovative premise. While technical concerns were noted, the potential utility and applicability of the described technology convinced the reviewers of its overall merit. The reviewers were uniformly enthusiastic about the potential of the proposed technology to advance the field of stem cell biology. Due to limitations of current instrumentation, it has not been possible to faithfully visualize cellular and subcellular processes that occur deep within living tissues. If successful, the proposed technology would enable stem cells and other objects of interest to be imaged in real time in their native environment, thus enabling a variety of studies to be performed that would not have been practical otherwise. Such a tool would be widely utilized and could greatly benefit all aspects of cell biology, including studies of stem cell behavior as well as in vivo engraftment for therapy. In terms of feasibility, the reviewers were confident in the qualifications of the research team. The proposal was well written, the research plan was straightforward, and the underlying premise was both innovative and sound. Although not definitive, the preliminary data were encouraging and spoke to the overall feasibility of the method. Despite their enthusiasm, however, the reviewers discussed several technical weaknesses that could diminish the overall impact of this effort. For example, it was unclear as to whether the bead quantity and types that were proposed would be sufficient for achieving the desired resolution. Furthermore, due to the observed increase in aberration at 25 microns, the reviewers questioned whether it would be realistic to image objects at a depth of several hundred microns, the level that would likely be necessary for this technology to be useful in the study of mouse tissues. In general, the reviewers felt that the qualifications of the research team were excellent. Although the track record of the principal investigator was judged to be appropriate but not very strong, the co-investigators were considered to be oustanding. Due to the complementary strengths of the collaborators, the team as a whole was considered an asset. Overall, this was an innovative and largely feasible proposal from a talented team of investigators with the potential to make significant contributions to the field of stem cell biology. PROGRAMMATIC REVIEW A motion was made to move this proposal from Tier 2, Recommended for Funding if Funds Available, to Tier 1, Recommended for Funding. Despite some technical uncertainties, the reviewers argued that this technology is needed, could be widely employed, and could be of practical utility both before and during translational research. The motion carried.