Eric A Price

Interests

Teaching

Here is my philosophy of teaching:It is my belief that a lecturer is well served by pursuing the following four critical components of instruction: knowledge, enthusiasm, organization, and investment.• To be knowledgeable is to make sure one is well-versed in one's subject. Being knowledgeable is evidenced by confidence in the accuracy of content when giving lectures. When an instructor is thoroughly knowledgeable, academic freedom in education is completely justified. By this, I mean the lecture hall becomes not only a forum for imparting information but also a forum for highlighting relevance to personal and public health (a treasured opportunity afforded to we who teach physiology), for providing historical perspective, for inspiring student inquiry, and for illuminating the significant role of current institutional (departmental) research within an academic discipline.• To be enthusiastic is to exhibit genuine excitement when teaching. Being enthusiastic is evidenced by a consistent demonstration of confidence over nervousness and fun over monotony. Confidence follows knowledge and practice, fun follows confidence (as well as through a natural affection for teaching), and in my opinion these two scales are critical in that they are used by students to gauge instructor competence. Enthusiasm for teaching is also evidenced by one’s own interest in a subject and a drive to incorporate new and engaging instructional techniques to better share one’s interest in the subject to improve student comprehension.• To be organized is to demonstrate thorough preparation. Being organized is evidenced by delivering well-designed lectures that not only present the topic at hand but also present the broad context into which the lecture’s topic fits. This permits an instructor to transition well between topics, to discuss each topic in proper context at the appropriate level, and to place conclude topics in such as way that they dovetail together to reinforce course themes. This could be described as a forward-minded teaching style, and teaching is this way can help the many students who struggle to comprehend the “big picture” in one’s course.• To be invested is to show students that one is dedicated to student success. Being invested is evidenced by concern for the course from the point of view of the student. By this I mean an instructor should be concerned with the clarity of lectures and the level of student comprehension. An instructor should also work to ensure fair assessment and to quickly address student concerns, whether those concerns are expressed in course evaluations or via other correspondence. Through such actions, an instructor shows they are committed to student success and demonstrates in part to students the high value of learning itself.

Research

Using computational tools to match experimental results for nucleic acid structural data to possible 3D structure conformations as predicted by computations tools I have helped to develop. Past collaborations have included matching EPR results for site-directed spin labeled nucleotides in RNA structures, but I would like to someday extend the applications to all manner of experimental investigation of nucleic acid structure.

Courses

Scholarly Contributions

Journals/Publications

• Popova, A. M., Hatmal, M. M., Frushicheva, M. P., Price, E. A., Qin, P. Z., & Haworth, I. S. (2012). Nitroxide sensing of a DNA microenvironment: mechanistic insights from EPR spectroscopy and molecular dynamics simulations. The journal of physical chemistry. B, 116(22), 6387-96.
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  The behavior of the nitroxide spin labels 1-oxyl-4-bromo-2,2,5,5-tetramethylpyrroline (R5a) and 1-oxyl-2,2,5,5-tetramethylpyrroline (R5) attached at a phosphorothioate-substituted site in a DNA duplex is modulated by the DNA in a site- and stereospecific manner. A better understanding of the mechanisms of R5a/R5 sensing of the DNA microenvironment will enhance our capability to relate information from nitroxide spectra to sequence-dependent properties of DNA. Toward this goal, electron paramagnetic resonance (EPR) spectroscopy and molecular dynamics (MD) simulations were used to investigate R5 and R5a attached as R(p) and S(p) diastereomers at phosphorothioate (pS)C(7) of d(CTACTG(pS)C(7)Y(8)TTAG). d(CTAAAGCAGTAG) (Y = T or U). X-band continuous-wave EPR spectra revealed that the dT(8) to dU(8) change alters nanosecond rotational motions of R(p)-R5a but produces no detectable differences for S(p)-R5a, R(p)-R5, and S(p)-R5. MD simulations were able to qualitatively account for these spectral variations and provide a plausible physical basis for the R5/R5a behavior. The simulations also revealed a correlation between DNA backbone B(I)/B(II) conformations and R5/R5a rotational diffusion, thus suggesting a direct connection between DNA local backbone dynamics and EPR-detectable R5/R5a motion. These results advance our understanding of how a DNA microenvironment influences nitroxide motion and the observed EPR spectra. This may enable use of R5/R5a for a quantitative description of the sequence-dependent properties of large biologically relevant DNA molecules.
• Cai, Q., Kusnetzow, A. K., Hideg, K., Price, E. A., Haworth, I. S., & Qin, P. Z. (2007). Nanometer distance measurements in RNA using site-directed spin labeling. Biophysical journal, 93(6), 2110-7.
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  The method of site-directed spin labeling (SDSL) utilizes a stable nitroxide radical to obtain structural and dynamic information on biomolecules. Measuring dipolar interactions between pairs of nitroxides yields internitroxide distances, from which quantitative structural information can be derived. This study evaluates SDSL distance measurements in RNA using a nitroxide probe, designated as R5, which is attached in an efficient and cost-effective manner to backbone phosphorothioate sites that are chemically substituted in arbitrary sequences. It is shown that R5 does not perturb the global structure of the A-form RNA helix. Six sets of internitroxide distances, ranging from 20 to 50 A, were measured on an RNA duplex with a known X-ray crystal structure. The measured distances strongly correlate (R(2) = 0.97) with those predicted using an efficient algorithm for determining the expected internitroxide distances from the parent RNA structure. The results enable future studies of global RNA structures for which high-resolution structural data are absent.
• Price, E. A., Sutch, B. T., Cai, Q., Qin, P. Z., & Haworth, I. S. (2007). Computation of nitroxide-nitroxide distances in spin-labeled DNA duplexes. Biopolymers, 87(1), 40-50.
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  Nanometer distances in nucleic acids can be measured by EPR using two 1-oxyl-2,2,5,5-tetramethylpyrroline radicals, with each label attached via a methylene group to a phosphorothioate-substituted backbone position as one of two phosphorothioate diastereomers (R(P) and S(P)). Correlating the internitroxide distance to the geometry of the parent molecule requires computational analysis of the label conformers. Here, we report sixteen 4-ns MD simulations on a DNA duplex d(CTACTGCTTTAG) .d(CTAAAGCAGTAG) with label pairs at C7/C19, T5/A17, and T2/T14, respectively. For each labeled duplex, four simulations were performed with S(P)/S(P), R(P)/R(P), S(P)/R(P), and R(P)/S(P) labels, with initial all trans label conformations. Another set of four simulations was performed for the 7/19-labeled duplex using a different label starting conformation. The average internitroxide distance r(MD) was within 0.2 A for the two sets of simulations for the 7/19-labeled duplex, indicating sufficient sampling of conformational space. For all three labeled duplexes studied, r(MD) agreed with experimental values, as well as with average distances obtained from an efficient conformer search algorithm (NASNOX). The simulations also showed that the labels have conformational preferences determined by the linker chemistry and label-DNA interactions. These results establish computational algorithms that allow use of the 1-oxyl-2,2,5,5-tetramethylpyrroline label for mapping global structures of nucleic acids.
• Qin, P. Z., Haworth, I. S., Cai, Q., Kusnetzow, A. K., Grant, G. P., Price, E. A., Sowa, G. Z., Popova, A., Herreros, B., & He, H. (2007). Measuring nanometer distances in nucleic acids using a sequence-independent nitroxide probe. Nature protocols, 2(10), 2354-65.
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  This protocol describes the procedures for measuring nanometer distances in nucleic acids using a nitroxide probe that can be attached to any nucleotide within a given sequence. Two nitroxides are attached to phosphorothioates that are chemically substituted at specific sites of DNA or RNA. Inter-nitroxide distances are measured using a four-pulse double electron-electron resonance technique, and the measured distances are correlated to the parent structures using a Web-accessible computer program. Four to five days are needed for sample labeling, purification and distance measurement. The procedures described herein provide a method for probing global structures and studying conformational changes of nucleic acids and protein/nucleic acid complexes.
• Chambers, E. J., Price, E. A., Bayramyan, M. C., & Haworth, I. S. (2003). Computation of DNA backbone conformations. Journal of biomolecular structure & dynamics, 21(1), 111-25.
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  We present an algorithm for the computation of 2'-deoxyribose-phosphodiester backbone conformations that are stereochemically compatible with a given arrangement of nucleic acid bases in a DNA structure. The algorithm involves the sequential computation of 2'-deoxyribose and phosphodiester conformers (collectively referred to as a backbone 'segment'), beginning at the 5'-end of a DNA strand. Computation of the possible segment conformations is achieved by the initial creation of a fragment library, with each fragment representing a set of bond lengths, bond angles and torsion angles. Following exhaustive searching of sugar conformations, each segment conformation is reduced to a single vector, defined by a specific distance, angle and torsion angle, that allows calculation of the O(1)' position. A given 'allowed' conformation of a backbone segment is determined based on its compatibility with the base positions and with the position of the preceding backbone segment. Initial computation of allowable segment conformations of a strand is followed by the determination of continuous backbone solutions for the strand, beginning at the 3'-end. The algorithm is also able to detect repeating segment conformations that arise in structures containing geometrically repeating dinucleotide steps. To illustrate the utility and properties of the algorithm, we have applied it to a series of experimental DNA structures. Regardless of the conformational complexity of these structures, we are able to compute backbone conformations for each structure. Hence, the algorithm, which is currently implemented within a new computer program NASDAC (Nucleic Acids: Structure, Dynamics and Conformation), should have generally applicability to the computation of DNA structures.

Poster Presentations

• Stanescu, C. I., Cohen, Z., & Price, E. A. (2016, October). Physiology Undergraduate Curricular Changes in Response to Program Assessment. Arizona Physiological Society. Tucson, AZ: American Physiological Society.

Others

• Chambers, E., Price, E. A., Bayramyan, M., & Haworth, I. (2001, APR). Computation of DNA conformational transitions: Base slippage in D(CTG)(N) triplet repeat DNA.. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY.