I AM WRITING THIS LETTER TO NOTIFY YOU OF MY TEAMS INTENT TO SUBMIT AN APPLICATION ENTITLED EFFECTS OF MICROGRAVITY ON THE RISKS OF SPACE RADIATION INDUCED LEUKEMOGENESIS IN RESPONSE TO NASA SPACE BIOLOGYS NRA NNH16ZTT001N GL ROSBIO APPENDIX A ENTITLED GENELAB INNOVATION AWARDS FOR TRANSLATIONAL SYSTEMS BIOLOGY AND INFORMATICS RESEARCH USING THE GENELAB DATA SYSTEM. WE WILL SPECIFICALLY BE MAKING USE OF DATA GENERATED AS PART OF GENELAB EXPERIMENT SETS GLDS 53 GLDS 55 AND GLDS 25 AS THE BASIS FOR THE NOVEL HYPOTHESIS TO BE TESTED IN THE CURRENT PROPOSAL MICROGRAVITY G ACTS IN CONCERT WITH SOLAR PARTICLE EVENT SPE AND GALACTIC COSMIC RAY GCR RADIATION TO PRODUCE DELETERIOUS EFFECTS ON THE HUMAN HEMATOPOIETIC SYSTEM WHICH MAY LEAD TO AN ENHANCED RISK OF LEUKEMOGENESIS AS A RESULT OF BOTH INCREASED GENOMIC DAMAGE TO CELLS OF THE HEMATOPOIETIC SYSTEM AND A REDUCED ABILITY OF THE IMMUNE SYSTEM TO RECOGNIZE AND CLEAR HEMATOPOIETIC CELLS THAT HAVE UNDERGONE MALIGNANT TRANSFORMATION AS A RESULT OF EXPOSURE TO SPE GCR RADIATION AND CONDITIONS OF MICROGRAVITY. DATA GENERATED FROM THE AFORE MENTIONED GENELAB STUDIES SUPPORTTHIS HYPOTHESIS AS THESE DATA HAVE SHOWN THAT G 1 INDUCES HIGHER LEVELS OF SPONTANEOUS DNA DAMAGE IN HUMAN HEMATOPOIETIC CELLS 2 MARKEDLY ALTERS THE ABILITY OF MATURE HUMAN IMMUNE CELLS TO RESPOND APPROPRIATELY TO STIMULI 3 DIMINISHES THE ABILITY OF HUMAN LYMPHOCYTES TO EFFICIENTLY REPAIR DNA DAMAGE IN RESPONSE TO IONIZING RADIATION AND 4 LEADS TO ALTERATIONS IN THE LEVELS OF MULTIPLE MIRNAS THAT HAVE BEEN IMPLICATED IN A VARIETY OF HUMAN HEMATOPOIETIC MALIGNANCIES. WE HAVE ALSO GENERATED A WEALTH OF DATA TO SUPPORT THE HYPOTHESIS THAT G AND SPACE RADIATION LIKELY ACT SYNERGISTICALLY TO INCREASE ASTRONAUT RISK OF LEUKEMOGENESIS DURING A PROLONGED MISSION BEYOND LEO. IN THE PRESENT PROPOSAL WE WILL BUILD UPON THESE DATA BY PERFORMING STUDIES TO DIRECTLY TEST THE ABILITY OFG TO INCREASE THE RISK OF LEUKEMIC TRANSFORMATION IN HUMAN HSC WHILE SIMULTANEOUSLY REDUCING THE ABILITY OF GENERATED IMMUNE CELLS FROM RECOGNIZING AND REMOVING ANY MALIGNANT CLONES THAT ARISE.