With this award, the Chemistry of Life Processes Program of the Chemistry Division in the Directorate for Mathematical and Physical Sciences, the Developmental Systems Cluster in the Division of Integrative Organismal Systems of the Directorate for Biological Sciences, and the CBET-Nano-Biosensing Program in the Directorate for Engineering are funding Dr. James Chen from Stanford University to develop lanthanide-based systems for the imaging of RNAs and proteins in vivo. RNA aptamers and polypeptide receptors that bind to lanthanide chelates and enhance their photoluminescence will be developed through iterative rounds of molecular evolution, selection, and amplification. The receptor/chelate pairs will then be used to detect subnanomolar levels of mRNAs and proteins in live zebrafish embryos, taking advantage of the long luminescence lifetimes of lanthanide complexes. In combination with genome editing using transcription activator-like effect nucleases, these technologies have the potential to enable the simultaneous observation of tissue patterning and organogenesis and the macromolecules that regulate these processes. Through this interdisciplinary approach, the study will help decode the dynamic genetic programs that give rise to complex organisms.
While currently embryonic development can be observed with single-cell resolution by time-lapse microscopy, the biological molecules that contribute to this remarkable transformation remain largely invisible. As a result, our understanding of how specific RNAs and proteins contribute to the formation of distinct tissues and organs is limited. This study develops new technologies that may overcome this hurdle by enabling the real-time detection of RNAs and proteins in live zebrafish embryos and other organisms. The approach is based on use of methods pertaining to different related disciplines, specifically synthetic chemistry, molecular imaging, and developmental biology. A scientifically multilingual cadre of graduate students and postdoctoral fellows will be trained. The project will also promote interdisciplinary research in scientific communities from developing countries through a chemical biology short-course at the University of São Paulo in Brazil and by exposing talented Brazilian graduate students to research at Stanford University.
