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About Dr. Frasch  

Wayne D. Frasch joined the faculty at Arizona State University in Fall 1989 where he is now a Professor and a member of the ASU Center for the Study of Early Events in Photosynthesis. He is an active participant in the Biomolecular Nanotechology graduate research training program supported by a National Science Foundation IGERT grant.

 

Dr. Frasch previously held a faculty position at the University of Michigan in Ann Arbor, and was a visiting research scientist at the Mayo Clinic. He has served on a NIH study section, and has been a Fellow of the Horace Rackham Foundation as well as the Eli Lilley Foundation. In 1985-1986, he served on the NSF/USDA/DOE advisory panel to establish the Plant Science Centers Program. In 1994, he was awarded the Golden Key National Honor Society Award for Excellence in Teaching.

 

Dr. Frasch’s primary research interest concerns the FₒF₁ ATP synthase. This enzyme is required by virtually every living organism to catalyze the conversion of energy from food or light (during photosynthesis) into ATP, a form of energy that can be used to drive most cellular processes. The enzyme is the smallest molecular motor known. As it operates a core of protein subunits rotates inside a group of stationary subunits. Each of three surrounding stationary subunits contains a catalytic site for the synthesis of ATP from ADP and phosphate that work in an alternating mechanism much like a three cylinder engine.

 

The F₁ portion of the enzyme that contains the catalytic sites can be removed from Fo. Under these conditions the F₁ has ATP hydrolysis activity that drives the rotation of the gamma subunit in the inner core of the protein. The rotation of the gamma subunit in single F₁ enzyme molecules can be observed under a microscope when the nonrotating subunits are attached to a cover slip and an optical probe is attached to the gamma subunit.

 

With grant support from the National Institutes of Health, the Frasch laboratory is examining the mechanism with which F₁ uses the hydrolysis of ATP to drive the rotation of the gamma subunit. In these studies, site-directed mutagenesis is used to change specific amino acid side chains in the protein. The enzyme that contains each mutant is then evaluated for differences in the ability to hydrolyze ATP and for the ATPase-dependent rotation of the gamma subunit as observed in single molecule experiments. The residues that are receiving the most intense scrutiny have some connection to those that serve as ligands to the magnesium cofactor of the enzyme. In previous work, the Frasch laboratory pioneered the combined use of EPR spectroscopy of vanadyl, a magnesium surrogate for F₁, with site-directed mutagenesis to identify how the metal ligands change with each step in catalysis. These ligand changes were shown to be essential to the sequential protein conformational changes in the catalytic mechanism.

 

Dr. Frasch’s laboratory is also using the F₁-ATPase as a biomolecular motor in the development of the Molecular Semaphore Device with funding from DARPA. This device uses the ability to detect the rotation of single F₁ molecules as a means to detect the hybridization of single molecules of DNA. The device has the potential to increase the sensitivity of detection of DNA microarrays to the ultimate single molecule level, and has received support from the defense department specifically to detect biological warfare agents like Anthrax. Drug testing and proteomics are additional potential applications of this device. The development of the single molecule technology for this device also has direct application to the basic research on the rotational mechanism of the F₁-ATPase in the Frasch laboratory.

 

Dr. Frasch received his Bachelors degree from Hope College in Holland, Michigan and his Ph.D. at the University of Kentucky in Lexington. He was an NSF predoctoral research fellow at the Marine Biological Laboratory, Woods Hole, Massachusetts, and did his postdoctoral work in the Biochemistry Department at the University of Wisconsin in Madison.

 

Patents:

Frasch, W. D., Chapsky, L., Chou, C., Zenhausern, F., and Goronkin, H. (2002) “Molecular Semaphore Device for Single Molecule Detection”

 

Frasch, W. D., and Chapsky, L. (2002) “A Polarization-Enhanced Detector for Nanoscale Rotational Motion Using Gold Nanorods”

 

Selected Publications

Frasch, W. D. and Sayre, R. E. (2002) “Remembering George Cheniae, Who Never Compromised His High Standards of Science.” Photosynthesis Research 70, 245-247.

 

Chen, W. and Frasch, W. D. (2001) “Interaction of the Catch-Loop Tyrosine Y317 with the Metal at Catalytic Site 3 of Chlamydomonas Chloroplast F₁-ATPase”, Biochemistry 40, 7729-7735.

 

Crampton, D. J., LoBrutto, R., and Frasch, W. D. (2001) “Identification of the P-loop Lysine as a Metal Ligand in the Absence of Nucleotide at Catalytic Site 3 of Chloroplast F₁-ATPase from Chlamydomonas reinhardtii”,Biochemistry 40, 3710-3716.

 

Frasch, W. D. (2000) “Vanadyl as a Probe of the Function of the F₁-ATPase-Mg2+ Cofactor” J. Bioenergetics and Biomembranes 32, 539-546.

 

Chen, W., Hu, C.-H., Crampton, D. J., and Frasch, W. D. (2000) “Characterization of the Metal Binding Environment of Catalytic Site 1 of Chloroplast F₁-ATPase from Chlamydomonas“, Biochemistry 39, 9393-9400.

 

Frasch, W. D. (2000) “The Participation of Metals in the Mechanism of the F₁-ATPase” Biochim. Biophys. Acta1458, 310-325.

 

Hu, C.-Y., Chen, W., and Frasch, W. D. (1999) “Metal Ligation by Walker Homology B Aspartate bD262 at Site 3 of the Latent but not Activated Form of the Chloroplast F₁-ATPase from Chlamydomonas reinhardtii” J. Biol. Chem. 274, 30481-30486.

 

Chen, W., LoBrutto, R., and Frasch, W. D. (1999) “EPR Spectroscopy of VO2+-ATP Bound to Catalytic Site 3 of Chloroplast F₁-ATPase from Chlamydomonas Reveals Changes in Metal Ligation Resulting from Mutations to the Phosphate-binding Loop Threonine (bT168).” J. Biol. Chem. 274, 7089-7094.

 

LoBrutto, R., Hamstra, B. J., Colpas, G. J., Pecoraro, V. L., and Frasch, W. D. (1998) "Electron Spin Echo Envelope Modulation Spectroscopy Reveals and Distinguishes Equatorial and Axial Nitrogen Ligands Bound to VO2+." J. Am. Chem. Soc. 120, 4410-4416.

 

Hamstra, B. J., Houseman, A. L. P., Colpas, G. J., LoBrutto, R., Frasch, W. D., and Pecoraro, V. L. "Structural and Solution Characterization of Mononuclear Vanadium(IV) Complexes that Help to Elucidate the Active Site Structure of the Reduced Vanadium Haloperoxidases." (1997) Inorganic Chem. 36, 4866-4874.

 

Hu, C.-Y., Houseman, A. L. P., Morgan, L., Webber, A. N., and Frasch, W. D. (1996) "Catalytic and EPR Studies of the E204Q mutant of the b Subunit of the chloroplast F₁-ATPase from Chlamydomonas reinhardtii.",Biochemistry 35, 12201-12211.

DRAFT: This module has unpublished changes.