Jonathan P. Davis, Ph.D.

Assistant Professor 209 Hamilton Hall 1645 Neil Avenue Columbus  OH  43210-1218 Office Phone: 614-247-2559 Lab Phone: 614-688-4467 Fax: 614-292-4888 davis.812@osu.edu

Education:
B.A., Mathematics and Physics, Greenville College, Greenville, IL
Ph.D., Biophysics, The Ohio State University, Columbus, OH

Research Area:
Elucidate the biochemical and physiological mechanisms that determine the kinetics of cardiac and skeletal muscle contraction and relaxation in health and disease through the engineering of proteins.

Davis Lab 2008

From left to right:  Benjamin Jones, Sean Little, Bin Liu, Kristopher Kline, Ryan Lee, Dr. Jonathan Davis

1) Determine the cellular and molecular basis of muscle contraction and relaxation.
2) Understand how calcium binding proteins/enzymes are appropriately “tuned” kinetically to respond to calcium transients in vitro and in vivo.
3) Modulate cellular function through the design and engineering of calcium binding proteins and/or their binding partners.

All biological systems utilize directly or indirectly calcium, and thus calcium binding proteins to perform the functions of daily life (even death). The EF-Hand motif is the most common structure used by proteins to sense and respond to fluctuations in cellular calcium. Different EF-hand sequences found in proteins display calcium sensitivities and kinetics that can vary by over 3 orders of magnitude. One of the goals of the laboratory is to decipher the amino acid code that dictates the calcium binding properties of proteins.
 

Biochemical model systems can be too simplistic to be physiologically relevant. Alternatively, physiological systems can be so complex that without simplified biochemical systems it would be impossible to understand the underlying mechanisms of function. One of the approaches of the laboratory is to study systems of increasing complexity ranging from isolated proteins to muscle with the goal to understand, explain and modify physiological phenomena through its biochemistry. Cardiac, skeletal and smooth muscle all use EF-hand proteins (troponin C for striated muscle and calmodulin for smooth muscle) to initiate contraction and relaxation. However, these particular calcium binding “switches” do not function in isolation, but as part of multi-subunit protein complexes (excluding the small cytosolic calcium buffering protein parvalbumin). Upon calcium binding these “switches” change their structure, typically exposing hydrophobic residues (yellow residues in the above figure) that then are used to bind and change the structure/function of other protein binding partners. These subsequent protein-protein interactions further modify the calcium binding properties of the EF-Hand proteins. Thus, in order to understand the physiological calcium binding properties of the proteins, biochemical model systems must be developed that incorporate all the protein influences on calcium binding. Another goal of the laboratory is to decipher the protein-protein influences that modulate the calcium binding properties of muscle proteins. 

Techniques Available:
The laboratory uses tools from the disciplines of Biochemistry, Biophysics, Molecular Biology and Physiology. Techniques include protein engineering, adenoviral protein transduction, fluorescence/absorbance spectroscopy, stopped-flow technology (rapid kinetic measurements) and laser flash induction of muscle contraction or relaxation (measurements for muscle mechanics), etc. The general philosophy of the laboratory is to learn and utilize any technique that is necessary to answer the fundamental questions of the systems being studied.

Publications (since 2006):
• Swartz DR, Yang Z, Sen A, Tikunova SB, Davis JP. Myofibrillar troponin exists in three states and there is signal transduction along skeletal myofibrillar thin filaments. J Mol Biol 361:420-435, 2006.
• Engel PL, Kobayashi T, Biesiadecki B, Davis JP, Tikunova SB, Wu S, Solaro RJ. Critical area within the near N-terminus of troponin I alters cross-bridge dependent activation of cardiac thin filaments. J Biol Chem 282:183-193, 2007.
• Davis JP, Alionte C, Kobayashi T, Solaro RJ, Swartz DR, Tikunova SB. Effects of thin and thick filament proteins on calcium binding and exchange with cardiac troponin C. Biophys J 92:3195-3206, 2007.
• Kreutziger KL, Gillis TE, Davis JP, Tikunova SB, Regnier M. Influence of enhanced troponin C Ca²⁺ binding affinity on cooperative thin filament activation in rabbit skeletal muscle. J Physiol  583:337-350, 2007.
• Norman C, Rall JA, Tikunova SB, Davis JP. Modulation of the rate of cardiac muscle contraction by troponin C constructs with various calcium binding affinities. Am J Physiol Heart Circ Physiol  293:H2580-2587, 2007.
• Monasky MM, Varian KD, Davis JP, Janssen PM. Dissociation of force decline from calcium decline by preload in isolated rabbit myocardium. Pflugers Arch In Press, 2008.
• Davis JP, Tikunova SB. Ca²⁺ exchange with troponin C and cardiac muscle dynamics. Cardiovasc Res In Press, 2008.
• Liang B, Chung F, Yang Q, Pavlov D, Gillis TE, Tikunova SB, Davis JP, Tibbits GF. The familial hypertrophic cardiomyopathy related cardiac troponin C mutation L29Q affects calcium binding and myofilament caontractility. Physiol Genomics In Press, 2008.