Project Grant 2145494

CAREER: EXTRACELLULAR HYDROGEN PEROXIDE AND NITRIC OXIDE DETECTION AND QUANTIFICATION VIA BIOCOMPATIBLE CARBON NANOTUBES -REACTIVE OXYGEN AND NITROGEN SPECIES (ROS AND RNS) ARE ESSENTIAL COMPONENTS IN CELL SIGNALING AND THEY ARE KNOWN TO PLAY AN IMPORTANT ROLE IN HEALTH AND DISEASE/INFLAMMATION?BOTH HELPFUL AND HARMFUL; HOWEVER, THEIR CONCENTRATIONS AND MECHANISMS DURING HEALTHY AND DISEASED STATES ARE LARGELY UNKNOWN. THIS CAREER PROJECT WILL ADVANCE THE UNDERSTANDING OF HOW ROS AND RNS LEVELS IMPACT THE FUNCTION OF CELLS AND TISSUES USING NANO-SCALE SENSORS TO QUANTIFY ROS/RNS CONCENTRATIONS. ULTIMATELY, UNDERSTANDING HOW ROS/RNS LEVELS CORRELATE WITH DISEASED CELLS AND USING NOVEL SENSORS TO SUBSEQUENTLY QUANTIFY THESE CONCENTRATIONS COULD PROVIDE QUICK DETECTION OF INFECTED INDIVIDUALS, THUS LEADING TO IMPROVED DIAGNOSTICS AND HEALTH OUTCOMES. INTEGRATED WITH THIS RESEARCH ARE EDUCATIONAL EFFORTS THAT AIM TO TEACH RURAL MIDDLE SCHOOL STUDENTS, UNDERGRADUATE AND GRADUATE STUDENTS, AND ADULTS OVER 50 AT THE OSHER LIFELONG LEARNING INSTITUTE (OLLI) ABOUT NANOTECHNOLOGY AND SENSORS. UNIVERSITY STUDENTS WILL RECEIVE TRAINING, MENTORSHIP, AND HANDS-ON EXPERIENCE WHILE DIRECTLY CONTRIBUTING TO THE RESEARCH OBJECTIVES AND WILL ENHANCE THEIR SCIENCE COMMUNICATION SKILLS BY ASSISTING WITH THE OUTREACH PROGRAMS, CREATING A RECIPROCAL RELATIONSHIP BETWEEN THE EDUCATION AND RESEARCH OBJECTIVES. PARTICIPANTS IN THE MIDDLE SCHOOL AND OLLI PROGRAMS WILL ENHANCE THEIR UNDERSTANDING OF NANOTECHNOLOGY AND SENSORS AND BE ABLE TO SHARE THEIR NEWLY ACQUIRED KNOWLEDGE WITH OTHERS, EXTENDING THE PROJECT?S IMPACT BEYOND THE INDIVIDUALS DIRECTLY PARTICIPATING IN THE PROGRAMS. THE INVESTIGATOR?S LONG-TERM CAREER GOAL IS TO DEVELOP AND USE SINGLE WALLED CARBON NANOTUBE (SWNT) SENSORS TO LEARN ABOUT BIOLOGICAL PHENOMENA WHILE PREPARING THE NEXT GENERATION FOR CAREERS IN NANOTECHNOLOGY AND SENSOR DEVELOPMENT. TOWARDS THIS GOAL, THIS PROJECT FOCUSES ON ADVANCING THE UNDERSTANDING OF ROS AND RNS IN CELL SIGNALING BY DEVELOPING A SINGLE WALLED CARBON NANOTUBE SENSOR SYSTEM THAT QUANTIFIES HYDROGEN PEROXIDE (H2O2) AND NITRIC OXIDE (NO) SIMULTANEOUSLY. RESEARCH OBJECTIVES INCLUDE TO: (1) DEVELOP A STERILE PLATFORM SYSTEM THAT CAN SIMULTANEOUSLY QUANTIFY H2O2 AND NO CONCENTRATIONS; (2) IDENTIFY THE CONCENTRATION PROFILES OF EXTRACELLULAR H2O2 AND NO ASSOCIATED WITH BREAST, SKIN, AND LYMPHOCYTE CELLS; AND (3) EVALUATE THE IMPORTANCE OF H2O2 AND NO IN CELLULAR PROLIFERATION, RELEASE OF INFLAMMATORY MARKERS, AND CELL MIGRATION. IT IS HYPOTHESIZED THAT DISEASED CELLS WILL HAVE SIGNIFICANTLY HIGHER LEVELS OF H2O2 AND NO AND THAT PROLIFERATION RATE, MIGRATION, AND INFLAMMATORY FACTORS CAN BE INCREASED OR DECREASED WITH THE ADDITION (CAUSING AN INCREASE) OR SCAVENGING (CAUSING A DECREASE) OF REACTIVE SPECIES. THIS PROGRAM REPRESENTS A NOVEL AND TRANSFORMATIVE APPROACH FOR QUANTIFYING H2O2 AND NO AND WILL ILLUMINATE BASIC FACTS ABOUT CELL SIGNALING THAT WERE PREVIOUSLY UNATTAINABLE. FURTHERMORE, THIS RESEARCH REPRESENTS A NEW MILESTONE IN THE FIELD OF CARBON NANOTUBES, WHICH HAS LARGELY FOCUSED ON DEVELOPING NEW SENSORS RATHER THAN USING THESE UNIQUE SENSORS TO UNDERSTAND HOW BIOLOGICAL SYSTEMS FUNCTION. FINDINGS FROM THIS RESEARCH WILL SERVE AS A ROADMAP FOR DETECTING OTHER SMALL MOLECULES IN THE FUTURE AS ADDITIONAL SENSORS ARE DEVELOPED. THIS PROJECT IS JOINTLY FUNDED BY THE BIOSENSING PROGRAM AND THE ESTABLISHED PROGRAM TO STIMULATE COMPETITIVE RESEARCH (EPSCOR). 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.