PROJECT SUMMARY Characterization of protein conformational changes is a crucial prerequisite to understanding biological functions on a molecular level. Circular dichroism (CD) spectroscopy has been an essential component of the biophysical tool kit for decades, exploiting the chiral properties of small molecules, proteins, and nucleic acids to provide information on molecular structure and its changes. For example, changes in secondary structure caused by protein unfolding (induced by perturbants such as temperature or pH), or folding (induced by the binding of a small molecule ligand, protein, or nucleic acid) can be quickly and easily quantified as changes in the far-UV CD spectrum. Separately, CD spectroscopy is also an essential technique in the study of chiral- selective properties of small molecules, including drugs, fluorescent dyes, and chemical catalysts designed to mimic enzymatic catalysis. Over the past decade, advancements in instrument optics and nitrogen purging, as well as the development of additional functionalities such as simultaneous fluorescence and absorbance detection, have further enhanced the utility of CD spectroscopy for biomedical studies. This proposal, in response to Program Announcement PAR-22-081, requests funds to purchase a state-of-the-art Jasco J-1500 CD spectropolarimeter to advance the research goals of University of Notre Dame scientists. This instrument will replace Notre Dame’s current Jasco J-815 instrument, which although still productive and carefully maintained for its >13-year lifespan, is optically inferior to modern instruments and operated by an obsolete computer. The new instrument will be housed in a recently renovated and expanded core facility; its acquisition is an important piece of a large effort currently underway to expand and improve research infrastructure at the University of Notre Dame. As such, supervision, care, and maintenance of this instrument will contribute to employment stability for core facility staff, while access to this state-of-the-art research equipment will continue to grow the research enterprise at Notre Dame.

PROJECT NARRATIVE Illumination of many biomolecules produces a characteristic optical signature. These signatures provide valuable information on the three-dimensional structure of the biomolecule, including how structural changes enable biomolecular function, and how mutations or other modifications affect function. Purchase of the proposed instrument will enable University of Notre Dame researchers to measure these optical signatures as part of a broader effort to understand the molecular details of a wide variety of biological processes, including protein folding and aggregation, bacterial pathogenesis, and cancer mechanisms.