Ph.D.
Professor
Biochemistry - CAFNR
Research at a glance
Area(s) of Expertise
Research Summary
The nature of protein interactions with other proteins in enzyme complexes and with components of cell surfaces continue to attract our interest. NMR spectroscopy is well suited to the fluidity of partners in these interactions. We have developed software to simplify complex changes in NMR spectra and in real-time cardiac MR imaging.
Protein interactions
Gatekeeper of synthesis of plant oils
The making of plant oils begins with the highly regulated first step of fatty acid biosynthesis. This is the conversion of the two carbons of acetyl-CoA to the three carbons of malonyl-CoA by acetyl-CoA carboxylase (ACCase). Some of the numerous subunits of the ACCase in chloroplasts regulate the flow of carbon into oil biosynthesis. We reported pH-sensing by the BADC and BCCP subunits, and suggested that it may influence enzyme activity during the daily light-dark cycle. Crosslinks recently suggested that the regulated catalytic subunit called biotin carboxylase forms dimers of dimers.
Membrane insertion and associations
Proteolytic activation of coronaviral Spike results in the mature N-terminus inserting in the host cell surface for viral fusion. We used NMR to demonstrate that encountering a membrane mimic transforms the fusion domain from disorder into a small wedge that inserts a surprising mix of charge and hydrophobicity into the membrane. Our MD simulations, gently guided by NMR-measured depths, subsequently suggest that the insertion of charge brought water into the membrane, inducing thinning and distortion of the bilayer.
Matrix metalloproteinases (MMPs) strongly influence tissue remodeling and inflammatory cell signaling in animals. We used NMR to demonstrate dual modes of binding of MMP-12, MMP-7, and the collagen-binding domain of MT1-MMP to membrane mimics. Such associations help account for strategic positioning of soluble MMPs for proteolysis at cell surfaces to influence cell signaling.
Complex signals simplified
We developed software to resolve many kinds of change from series of complicated spectra or images. Examples of the changes followed by NMR spectra include ligand binding, protein unfolding, and drug screening. Our TREND software for NMR is introduced and available at https://trend.missouri.edu/. NMRhub also hosts TREND for the research community. We adapted the approach to track heartbeats and mitigate breathing motion in free-breathing cardiac MRI, which is now patented. New insights into irregular heartbeats may also be possible.
Educational computer games for biochemistry
Some topics in biochemistry are perennially difficult. We and Adroit Studios collaborated to develop prototypes of computer games to help with a few of the trouble spots. The games of Emergence of the Biomolecules that regard charge of amino acids, transcription, and the genetic code are available online.
Educational background
- Ph.D. Biophysics, University of Illinois Urbana-Champaign
- B.S. Biochemistry/Computer Science, Oklahoma State University