CAREER: Measuring the Structural Transitions of Electrosprayed Proteins

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With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Ian Webb and his group at Indiana University-Purdue University Indianapolis are developing methods to investigate how proteins change their structure as they transition from liquid phase to gas phase. This work is important as it has the potential to significantly increase the understanding of protein structure and how it changes during electrospray ionization (ESI). The studies have the potential to illuminate which specific regions of proteins are responsible for compaction and expansion in the gas phase. Through interaction with industrial partners, research results are to be disseminated to other laboratories which will increase the impact of the methods and contribute to the advancement of available infrastructure for biomolecular structural analysis. Individuals and families living near the Children's Museum of Indianapolis will benefit from the education plan which aims to broaden exposure to STEM. The use of mass spectrometry to study structures of proteins and protein complexes is widespread. However, the extent which proteins keep their native structures inside a mass spectrometer is under debate. This proposed research will use mass spectrometric tools to directly determine the changes in structure to natively folded proteins during mass spectrometric analyses with chemical probes. Successful implementation of the proposed project will lead to a greater understanding of the side chain chemistries and structural motifs that are either stabilized or destabilized in solution, the gas phase, or in the transition between solution and gas phase. This research also includes an integrated educational plan with the goal of bringing a structural mass spectrometry experiments to local Indianapolis community children ages 6-12, parents/guardians, and educators in an exciting and informative STEM learning experience at the Children’s Museum of Indianapolis. The Children’s Museum’s urban location, free admission to individuals and families living within six surrounding neighborhoods, and many STEM learning resources attract a diverse group of attendees, with great potential to increase interest in STEM from historically excluded families in these communities. This partnership between the Webb laboratory and the Children’s Museum will make chemical measurements more accessible, allowing individuals from historically excluded groups to participate directly in STEM experiments.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.