Not listed
CAREER: EXPERIMENTAL AND COMPUTATIONAL STUDIES OF BIOMOLECULAR TOPOLOGY -NON TECHNICAL SUMMARY EVERYTHING WE MAKE, WE MAKE OUT OF ATOMS OR MOLECULES. WE HAVE A GOOD UNDERSTANDING OF HOW ATOMS AND SIMPLE MOLECULES BEHAVE, BUT IT IS HARDER TO UNDERSTAND MORE COMPLICATED MOLECULES. SOME OF THE MORE COMPLICATED MOLECULES ARE CONNECTED IN WAYS THAT SIMPLER MOLECULES AREN?T. WHERE SIMPLE MOLECULES MIGHT CONNECT LIKE LEGO BRICKS, MORE COMPLICATED MOLECULES MIGHT CONNECT LIKE LINKS ON A CHAIN. THE CHALLENGE IS THAT MOLECULES ARE VERY SMALL, TOO SMALL TO SEE WITH A MICROSCOPE, AND TOO FAST TO RECORD WITH A CAMERA. WE OVERCOME THIS CHALLENGE IN TWO WAYS. ONE IS BY USING BIGGER MOLECULES. DNA IS BEST KNOWN FOR CONTAINING OUR GENETIC CODE, BUT IT?S ALSO JUST AN EXTREMELY LARGE MOLECULE THAT WE CAN STUDY IN A MICROSCOPE. WE CAN DO EXPERIMENTS WITH DNA TO LEARN ABOUT HOW MOLECULES BEHAVE, AND APPLY THOSE LESSONS TO SMALLER MOLECULES. FOR EXAMPLE, WE MEASURE HOW STRETCHY A SINGLE DNA MOLECULE IS, AND USE THAT INFORMATION TO UNDERSTAND HOW THE MOLECULES THAT MAKE UP RUBBER BECOME STRETCHY. THE OTHER WAY IS TO USE COMPUTER SIMULATIONS, WHICH CAN SHOW US HOW MOLECULES WOULD BEHAVE IF WE COULD SEE THEM. THE MAIN MOLECULES STUDIED IN THIS PROJECT ARE CALLED KINETOPLASTS, WHICH ARE LIKE MEDIEVAL CHAINMAIL ARMOR MADE OF THOUSANDS OF CONNECTED LOOPS OF DNA. WE STUDY THESE WITH A MICROSCOPE, AND WITH COMPUTER SIMULATIONS, TO UNDERSTAND HOW MUCH SMALLER CHAINMAIL-LIKE MOLECULES, WHICH CHEMISTS ARE NOW LEARNING TO MAKE, WOULD BEHAVE. IN THE FUTURE, OUR UNDERSTANDING OF CHEMICAL CHAINMAIL MOLECULES COULD ALLOW NEWER, FANCIER MATERIALS AND NANOMACHINES CREATED ATOM BY ATOM, IF WE FIRST UNDERSTAND DNA CHAINMAIL. WE WILL ALSO TEACH A NEW GENERATION OF STUDENTS TO STUDY MOLECULES, BY HAVING THEM TAKE MICROSCOPIC VIDEOS OF DROPLETS FULL OF MOLECULES AS THEY EVAPORATE. SINCE NOBODY HAS OBSERVED THOSE SPECIFIC MOLECULES EVAPORATING IN THAT WAY BEFORE, THE STUDENTS WILL LEARN WHAT IT?S LIKE TO DISCOVER SOMETHING NEW, IN ADDITION TO LEARNING HOW TO DO THE EXPERIMENTS. AS PART OF THE EDUCATIONAL ASPECTS OF THIS GRANT, STUDENTS AT A MINORITY-SERVING PRIMARILY-UNDERGRADUATE INSTITUTION WILL CARRY OUT ORIGINAL RESEARCH AS PART OF A COURSE-BASED UNDERGRADUATE RESEARCH EXPERIENCE. THE EXPERIENCE OF A NEW DISCOVERY WILL BUILD A SENSE OF BELONGING IN THE SCIENTIFIC COMMUNITY AND SUPPORT THEIR IDENTITIES AS SCIENTISTS RATHER THAN JUST SCIENCE STUDENTS. TECHNICAL SUMMARY THE GOAL OF THIS PROJECT IS TO UNDERSTAND THE RELATIONSHIP BETWEEN MOLECULE TOPOLOGY AND MATERIAL PROPERTIES OF COMPLEX BIOPOLYMERS THROUGH SINGLE-MOLECULE EXPERIMENTS AND COARSE-GRAINED SIMULATIONS. BIOPOLYMERS SERVE AS A MESOSCOPIC SYSTEM ON THE MICRON SCALE ANALOGOUS TO SYNTHETIC POLYMERS ON THE NANOMETER SCALE. THE EXPERIMENTS WILL LARGELY FOCUS ON SINGLE-MOLECULE FLUORESCENCE MICROSCOPY. KINETOPLASTS, WHICH ARE PLANAR NETWORKS OF TOPOLOGICALLY LINKED DNA, WILL BE STUDIED AS A MODEL SYSTEM FOR SYNTHETIC POLYCATENANES AND THERMALIZED GRAPHENE. IN PARTICULAR, WE ARE INTERESTED IN HOW THE TOPOLOGY OF THEN NETWORK, WHICH CAN BE TUNED BY THE ACTION OF ENZYMES, EFFECTS THE ELASTIC RESPONSE TO KINETOPLASTS IN MICROFLUIDIC SHEAR FLOW. WE WILL ALSO DEVELOP ASSAYS TO USE GENOMIC-LENGTH DNA AS A TRACER POLYMER IN ACTIVE FLUIDS, WHICH DRIVE THEIR OWN INTERNAL COMPLEX FLOWS THROUGH THE CONVERSION OF CHEMICAL ENERGY. THE FLUCTUATIONS AND CONFORMATIONS OF THE MOLECULE WILL BE USED TO DETERMINE HOW LIFE-LIKE SYSTEMS APPROACH AND AVOID MAXIMUM-ENTROPY STATES, ESTABLISHING RULES THAT HELP US UNDERSTAND THE PHYSICS OF LIFE. ADDITIONALLY, WE WILL EXPLORE THE USE OF PARTIAL DENATURATION (A TOPOLOGICAL CHANGE IN LINEAR DNA) TO IMPROVE NANOPORE GENOMIC MAPPING TECHNOLOGY. SIMULATIONS WILL USE LANGEVIN DYNAMICS AND GRADIENT OPTIMIZATION TO STUDY THE RELATIONSHIP BETWEEN THE TOPOLOGY OF MOLECULAR CHAINMAIL AND THE LARGE-SCALE STRUCTURE OF THE SHEETS THAT THEY FORM, AS WELL AS TO INVESTIGATE THE RELATIONSHIP BETWEEN DENATURATION TRANSITIONS AND KNOTTED MOLECULAR TOPOLOGIES. AS PART OF THE BROADER IMPACTS OF THIS GRANT, STUDENTS AT A MINORITY-SERVING PRIMARILY-UNDERGRADUATE INSTITUTION WILL CARRY OUT ORIGINAL RESEARCH AS PART OF A COURSE-BASED UNDERGRADUATE RESEARCH EXPERIENCE, INITIALLY STUDYING NEMATIC LIQUID CRYSTALS IN MARANGONI FLOW. THE EXPERIENCE OF A NEW DISCOVERY WILL BUILD A SENSE OF BELONGING IN THE SCIENTIFIC COMMUNITY AND SUPPORT THEIR IDENTITIES AS SCIENTISTS RATHER THAN JUST SCIENCE STUDENTS. 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.
$160.2k 1/3/24