R01AI193502

TREGS: THE FORCE IS STRONG IN THIS ONE - ABSTRACT/SUMMARY THE VITAL PURPOSE OF REGULATORY T CELLS (TREGS) IS TO SUPPRESS IMMUNE RESPONSES AGAINST SELF IN AN ANTIGEN SPECIFIC MANNER. IN ADDITION THEY PARTICIPATE IN CANCER AND INFECTIOUS DISEASE. TREGS RECOGNIZE ANTIGEN VIA THEIR T CELL RECEPTOR (TCR), YET THE FUNDAMENTAL MEASURE OF HOW TREGS DIFFER FROM EFFECTOR T CELLS (TEFF) WHEN BINDING ANTIGENS IS UNKNOWN. THEREFORE, A THOROUGH UNDERSTANDING OF THE TRIGGERS THAT OCCUR IN TREGS FOLLOWING RECOGNITION OF ANTIGEN WOULD PROVIDE A BASE THAT COULD BE EXPLOITED TO BETTER UNLOCK THEIR THERAPEUTIC POTENTIAL. HERE, WE WILL DISSECT THE INTERACTION BETWEEN TCR AND ANTIGEN USING SENSITIVE TECHNOLOGIES TO MEASURE PARAMETERS GOVERNING TCR RECOGNITION OF ANTIGEN WITH A FOCUS ON THE DYNAMIC INTERFACE OF THE BOND. TYPICALLY, AFFINITY AND BOND LIFETIME BETWEEN TCR AND ANTIGEN ARE THE FOCUS OF RESEARCH IN THE FIELD. OF NOTE, ALL T CELLS APPLY FORCE TO THE BOND BETWEEN TCR AND ANTIGEN, WHICH IS ULTIMATELY REFLECTED BY CHANGES IN HOW LONG THE PROTEINS INTERACT. IT IS THE AMOUNT OF FORCE THAT WE PROPOSE TO FOCUS ON IN THE GRANT PROPOSAL. IN OUR PRELIMINARY WORK, WE DISCOVERED DIFFERENCES IN AMOUNT OF FORCE BETWEEN THAT CAN OCCUR FOR THE TREG TCR INTERACTION WITH ANTIGEN AS OPPOSED TO TEFF CELLS. WE ALSO IDENTIFIED PROTEIN(S) EXPRESSED BY TREGS THAT COULD EXPLAIN THESE DIFFERENCES IN THE CELLULAR FORCES DURING THE INTERACTION. WE THEREFORE HYPOTHESIZE THAT THESE DIFFERENCES ARE FUNDAMENTALLY WHAT MAKE TREGS UNIQUE AND DETERMINE THEIR OPTIMAL SUPPRESSIVE ACTIVITY. WE HAVE DESIGNED THREE AIMS TO TEST THIS HYPOTHESIS. THUS, OUR PROPOSED WORK WILL BE THE FIRST TO INVESTIGATE THE AMOUNT OF FORCE AS A POTENT BIOMARKER FOR TREGS THAT DICTATES THEIR SUPPRESSIVE PHENOTYPE. IN ADDITION, OUR PROJECT WILL PROVIDE NOVEL INSIGHT INTO THE CURRENTLY UNKNOWN MECHANISMS GOVERNING TREG BIOLOGY WITH IMPACT FOR THEIR THERAPEUTIC USE.

University Of Utah

<P>THE GOALS ARE:</P><UL><LI>TO FOSTER FUNDAMENTAL CREATIVE DISCOVERIES, INNOVATIVE RESEARCH STRATEGIES, AND THEIR APPLICATIONS AS A BASIS FOR ULTIMATELY PROTECTING AND IMPROVING HEALTH;</LI><LI>TO DEVELOP, MAINTAIN, AND RENEW SCIENTIFIC HUMAN AND PHYSICAL RESOURCES THAT WILL ENSURE THE NATION'S CAPABILITY TO PREVENT DISEASE;</LI><LI>TO EXPAND THE KNOWLEDGE BASE IN MEDICAL AND ASSOCIATED SCIENCES IN ORDER TO ENHANCE THE NATION'S ECONOMIC WELL-BEING AND ENSURE A CONTINUED HIGH RETURN ON THE PUBLIC INVESTMENT IN RESEARCH; AND</LI><LI>TO EXEMPLIFY AND PROMOTE THE HIGHEST LEVEL OF SCIENTIFIC INTEGRITY, PUBLIC ACCOUNTABILITY, AND SOCIAL RESPONSIBILITY IN THE CONDUCT OF SCIENCE.</LI></UL><P>IN REALIZING THESE GOALS, THE NIH PROVIDES LEADERSHIP AND DIRECTION TO PROGRAMS DESIGNED TO IMPROVE THE HEALTH OF THE NATION BY CONDUCTING AND SUPPORTING RESEARCH:</P><UL><LI>IN THE CAUSES, DIAGNOSIS, PREVENTION, AND CURE OF HUMAN DISEASES;</LI><LI>IN THE PROCESSES OF HUMAN GROWTH AND DEVELOPMENT;</LI><LI>IN THE BIOLOGICAL EFFECTS OF ENVIRONMENTAL CONTAMINANTS;</LI><LI>IN THE UNDERSTANDING OF MENTAL, ADDICTIVE AND PHYSICAL DISORDERS; AND</LI><LI>IN DIRECTING PROGRAMS FOR THE COLLECTION, DISSEMINATION, AND EXCHANGE OF INFORMATION IN MEDICINE AND HEALTH, INCLUDING THE DEVELOPMENT AND SUPPORT OF MEDICAL LIBRARIES AND THE TRAINING OF MEDICAL LIBRARIANS AND OTHER HEALTH INFORMATION SPECIALISTS.</LI></UL>

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Salt Lake City, Utah 841121100 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-25-301)