RNA WORLD THEORIES FEATURE PROMINENTLY IN ORIGINS-OF-LIFE MODELS WHICH PROPOSE THAT RNA OR A SIMILAR POLYMER PLAYED MAJOR ROLES IN BIOLOGICAL CATALYSIS IN ADDITION TO STORING HERITABLE GENETIC INFORMATION. WHILE SOME RNA WORLD ELEMENTS ARE WELL SUPPORTED BY EXPERIMENTAL DATA THE BIOLOGICAL VIABILITY OF SUCH RIBO-ORGANISMS REMAINS SPECULATIVE OR REQUIRES EXTRAPOLATION WELL BEYOND THE EXISTING DATA. IN PARTICULAR IT IS WELL-ESTABLISHED THAT RNA CAN PROMOTE SEVERAL CLASSES OF CHEMICAL REACTIONS IN SINGLE-TURNOVER FORMAT WITH NON-BIOLOGICAL SUBSTRATES BUT IT IS UNKNOWN WHETHER RNA CAN PROVIDE THE NECESSARY CATALYSIS TO SUPPORT COMPLEX CELLULAR FUNCTIONS OR HOW SUCH CATALYSTS MIGHT EMERGE. INDEED THE DEARTH OF ROBUST RNA CATALYSTS FOR SMALL MOLECULE TRANSFORMATION IS THE SINGLE BIGGEST BOTTLENECK IN THE CONSTRUCTION OF MODEL RIBO-ORGANISMS. A LONG-TERM GOAL OF OUR CONSORTIUM IS TO DEFINE THE POTENTIAL OF RNA TO SUSTAIN CELLULAR METABOLISM AND TO FULLY BRIDGE THE GAP BETWEEN BOTTOM-UP AND TOP-DOWN APPROACHES TO RNA WORLD RESEARCH THEREBY TOUCHING ON BOTH THE PCE3 AND FECM RESEARCH COLLABORATIVE NETWORKS (RCNS). THE PROPOSED RESEARCH WILL PROVIDE EXPERIMENTAL UNDERPINNING TO A CRITICAL MISSING PIECE OF THE RNA WORLD PUZZLE: EMERGENCE OF ROBUST TRULY CATALYTIC MULTIPLE TURNOVER RIBOZYMES AS PRECURSORS TO CONTEMPORARY METABOLIC PATHWAYS. METHODS/TECHNIQUES/APPROACH: THE TEAM COMPRISES 12 FACULTY FROM 8 INSTITUTIONS WITH EXPERTISE IN RNA BIOCHEMISTRY STRUCTURAL BIOLOGY ENZYMOLOGY RIBOZYME SELECTION SYNTHETIC ORGANIC CHEMISTRY BACTERIOLOGY SYNTHETIC BIOLOGY SYSTEMS BIOLOGY MODELING AND INFORMATICS OF EVOLVING RNA POPULATIONS. RELEVANCE TO NASA OBJECTIVES: AN RNA WORLD COULD PROVIDE A BRIDGE BETWEEN BOTTOM-UP AND TOP-DOWN APPROACHES THAT ARE AT THE HEART OF THE PCE3 AND FECM RESEARCH COORDINATION NETWORKS.