R35GM145323

SYNTHESIS AT THE INTERFACE OF CHEMISTRY AND BIOLOGY - PROJECT SUMMARY/ABSTRACT

THIS PROPOSAL EXPLORES THREE MAJOR ASPECTS OF SYNTHETIC BIOLOGY- ALL UNDER THE RELATED THEME OF THE EVOLUTION OF LIFE. A LOOK FORWARD INTO EVOLUTION BY CREATING ORGANISMS WITH AN EXPANDED GENETIC CODE, AND A LOOK BACK INTO EVOLUTION BY EXPLORING THE EVOLUTION OF MITOCHONDRIA IN A WELL- DEFINED “SYNTHETIC” ENDOSYMBIONT SYSTEM, AND BY EXPLORING ONE POSSIBLE MECHANISM FOR THE TRANSITION FROM THE RNA TO DNA WORLD THROUGH THE GENERATION AND CHARACTERIZATION OF BACTERIA WITH CHIMERIC DNA-RNA GENOMES.

SPECIFICALLY, WE WILL GENETICALLY ENCODE D-AMINO ACIDS IN BACTERIA AND CREATE AND APPLY A GENETICALLY ENCODED TOOL TO STUDY PROTEIN FOLDING/UNFOLDING ON A SUB-MICROSECOND TIMESCALE. WE WILL BEGIN TO MINIMIZE OUR BACTERIAL ENDOSYMBIONT GENOME BY DELETING METABOLIC AND CELL WALL BIOSYNTHETIC GENES, AS WELL AS EXPLORING THOSE FACTORS THAT CONTRIBUTE TO THE STABILITY OF THIS CHIMERIC SYSTEM. WE WILL ALSO CREATE A BIORTHOGONAL REPLICATION SYSTEM AND USE IT TO EXPLORE THOSE FACTORS THAT ALLOW THE INCORPORATION OF LARGE NUMBERS OF RIBONUCLEOTIDES INTO BACTERIAL DNA.

Scripps Research Institute

THE NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES (NIGMS) SUPPORTS BASIC RESEARCH THAT INCREASES OUR UNDERSTANDING OF BIOLOGICAL PROCESSES AND LAYS THE FOUNDATION FOR ADVANCES IN DISEASE DIAGNOSIS, TREATMENT, AND PREVENTION. NIGMS ALSO SUPPORTS RESEARCH IN SPECIFIC CLINICAL AREAS THAT AFFECT MULTIPLE ORGAN SYSTEMS: ANESTHESIOLOGY AND PERI-OPERATIVE PAIN; CLINICAL PHARMACOLOGY COMMON TO MULTIPLE DRUGS AND TREATMENTS; AND INJURY, CRITICAL ILLNESS, SEPSIS, AND WOUND HEALING. NIGMS-FUNDED SCIENTISTS INVESTIGATE HOW LIVING SYSTEMS WORK AT A RANGE OF LEVELSFROM MOLECULES AND CELLS TO TISSUES AND ORGANSIN RESEARCH ORGANISMS, HUMANS, AND POPULATIONS. ADDITIONALLY, TO ENSURE THE VITALITY AND CONTINUED PRODUCTIVITY OF THE RESEARCH ENTERPRISE, NIGMS PROVIDES LEADERSHIP IN SUPPORTING THE TRAINING OF FUTURE SCIENTISTS AND DEVELOPING RESEARCH CAPACITY THROUGHOUT THE COUNTRY.

93.859 - Biomedical Research and Research Training

National Institute of General Medical Sciences (NIGMS) [HHS - NIH]

La Jolla, California 920371000 United States

Single Zip Code

Maximizing Investigators' Research Award (R35 - Clinical Trial Optional) (PAR-19-367)

Amendment Since initial award the total obligations have increased 615% from $479,397 to $3,428,034.