Project Grant 2514977

INTBIO: COLLABORATIVE RESEARCH: FUNCTIONAL SYNERGY BETWEEN DISORDERED PROTEINS AND THEIR ENVIRONMENT IN DESICCATION PROTECTION -AS OUR CLIMATE CHANGES, ANIMALS AND PLANTS ARE INCREASINGLY EXPOSED TO DEHYDRATION. REMARKABLY, A COMMON STRATEGY THAT HAS EVOLVED TO HELP ORGANISMS ACROSS ALL KINGDOMS OF LIFE DEAL WITH DESICCATION IS THROUGH THE SYNTHESIS OF A SPECIAL CLASS OF PROTEINS KNOWN AS INTRINSICALLY DISORDERED PROTEINS. DESPITE THEIR IMPORTANCE IN PROTECTING ANIMALS AND PLANTS FROM DRYING OUT, HOW THESE PROTEINS WORK IS UNRESOLVED. THIS PROJECT WILL COMBINE EXPERIMENTS THAT SPAN INDIVIDUAL MOLECULES TO WHOLE ORGANISMS TO UNDERSTAND HOW DISORDERED PROTEINS PROVIDE PROTECTION FROM DEHYDRATION ACROSS ALL KINGDOMS OF LIFE. AS PART OF THIS STUDY, THIS PROJECT WILL RECRUIT STUDENTS FROM RURAL COMMUNITIES VIA REMOTE-LEARNING AND INCLUDE THEM IN CUTTING EDGE, INTERDISCIPLINARY RESEARCH WHICH WILL FACILITATE THEIR INTEGRATION INTO THE US STEM WORKFORCE. PROTEOMES ACROSS ALL KINGDOMS OF LIFE CONTAIN A SIGNIFICANT FRACTION OF SEQUENCES THAT ARE INTRINSICALLY DISORDERED AND DO NOT ADOPT A STABLE THREE-DIMENSIONAL STRUCTURE. INSTEAD, THESE SEQUENCES EXIST IN AN ENSEMBLE OF RAPIDLY INTERCONVERTING CONFORMATIONS THAT CAN BE HIGHLY SENSITIVE TO CHANGES IN THE CELLULAR ENVIRONMENT IN WHICH THEY FUNCTION. INTERESTINGLY, MANY OF THESE DISORDERED PROTEINS ARE IMPLICATED IN MEDIATING RESISTANCE TO ENVIRONMENTAL STRESSES, INCLUDING DESICCATION, IN WHICH THE PHYSICAL-CHEMICAL COMPOSITION OF THE CELL CHANGES DRAMATICALLY. THE GOAL OF THIS PROJECT IS TO GAIN A HOLISTIC UNDERSTANDING OF HOW DISORDERED PROTEINS AND THE CELLULAR ENVIRONMENT COME TOGETHER TO PROVIDE PROTECTION TO THE CELL DURING EXTREME DESICCATION. TOWARDS THIS GOAL, THE PROJECT WILL EMPLOY A MULTILEVEL, INTERDISCIPLINARY, AND INTEGRATED APPROACH. STARTING AT THE MOLECULAR LEVEL, IN VITRO AND COMPUTATIONAL EXPERIMENTS WILL BE PERFORMED THAT WILL PROVIDE INSIGHT INTO HOW DESICCATION-PROTECTIVE DISORDERED PROTEINS FUNCTION IN CONJUNCTION WITH WELL DEFINED AND CONTROLLABLE ENVIRONMENTS. THIS INFORMATION WILL BE INTEGRATED WITH HIGH THROUGHPUT, SEQUENCING-BASED STUDIES OF DISORDERED PROTEIN-MEDIATED DESICCATION PROTECTION PERFORMED IN YEAST (CELLULAR LEVEL), AND A MULTICELLULAR ANIMAL MODEL (THE ROUNDWORM, CAENORHABDITIS ELEGANS, ORGANISMAL LEVEL). THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.