Research Interests   Multinuclear Magnetic Resonance, Metal Homeostasis, Zinc-Finger Transcription Factor Activation, Alzheimer's Disease and Immunophilins

My laboratory is involved with the development and application of state-of-the-art multinuclear, multidimensional magnetic resonance methods to elucidate the structure, dynamics and mechanism of action of biological macromolecules. The strategy that is frequently used to focus on a particular aspect of a complex biological system such as an enzyme's active site or intermediates in the reaction profile, is the selective observation of less abundant nuclei present naturally or incorporated by specific biosynthetic or chemical labeling procedures. Specific systems under current investigation include: metalloproteins involved in metal homeostasis, metallothioneins, which includes studies of their role in the activation of zinc-finger containing transcription factors and the physiological role of the brain specific metallothionein, MT3, in Alzheimer's disease; and molecules involved in the immune response, the immunosuppressive drug cyclosporin A (CsA), and its cytosolic receptor protein, cyclophilin (CyP) and the penultimate interaction of the CsA:CyP complex with calcineurin.

Another area of past active research involved fundamental studies of factors affecting the relaxation (MRI) of protons in tissue with applications to clinical magnetic resonance imaging techniques.

Recent Publications
El Ghazi, I., Martin, B. L., and Armitage, I. M., Metallothionein-3 is a Component of a Multiprotein Complex in the Mouse Brain", Exp Biol Med, 231, 1500-1506 (2006). PubMed

Martin, B.L. , Tokheim, A.M., McCarthy, P.T., Doms, B.S., Davis, A.A. and Armitage, I.M. "Metallothionein-3 and neuronal nitric oxide synthase levels in brains from the Tg2576 mouse model of Alzheimer's disease." Molecular and Cellular Biochemistry, 286, 129-136. (2006) E-Journal

Lahti, D. W., Hoekman, J. D., Tokheim, A. M., Martin, B. L., and Armitage, I. M., "Identification of Mouse Brain Proteins Associated with Isoform 3 of Metallothionein", Protein Science, 14, 1151-1157 (2005). PubMed

Tokheim, A. M., Armitage, I. M., and Martin, B. L., "Antiserum Specific for the Intact Isoform-3 of Metallothionein", J. Biochem. Biophys. Methods, 63, 43-52 (2005). PubMed

Zangger, K. and Armitage, I. M., "Metallothionein" in Handbook of Metalloproteins , Volume 3, W. Bode, M. Cygler and A. Messerschmidt (eds) John Wiley & Sons, 351-364, (2004).

Cobine, P. A., McKay, R. T., Zangger, K., Dameron, C. T., and Armitage, I. M., "Solution Structure of Cu6 Metallothionein from the fungus Neurospora crass a," Eur. J. Biochem. (now FEBS J. ) 271 , 4213-4221 (2004). PubMed

Zangger, K. and Armitage, I. M. (2002) "Dynamics of Interdomain Interactions in Mammalian Metallothioneins," J. Inorg. Biochem., 88 ,(2), 135-143. PubMed

Zangger, K., Shen, G., Oz, G., Otvos, J.D. and Armitage, I.M., (2001) "Oxidative Dimerization in Metallothionein is a Result of Intermolecular Disulfide Bonds between Cysteines in the a-Domain," Biochem. J., 359, 353-360. PubMed

Oz, G., Zangger, K., and Armitage, I.M., (2001) "Three-dimensional Structure and Dynamics of a Brain Specific Growth Inhibitory Factor: Metallothionein-3," Biochemistry, 40, 11433-11441. PubMed

Zangger, K., Oz, G., Haslinger, E., Kunert, O. and Armitage, I.M., (2001) "Nitric Oxide Selectively Releases Metals from the N-terminal Domain of Metallothioneins: Potential Role at Inflammatory Sites," FASEB J., 15 (7): 1303-5. FASEB J

Zangger, K. Oz, G., and Armitage, I.M., (2000) "Re-evaluation of the Binding of ATP to Metallothioneins", J. Biol. Chem. 275:7534-8. PubMed.

Zangger, K. and Armitage, I.M. (2000) "The Accordian-HMQC:Heteronuclear Correlations Over a range of Coupling Constants," Magn. Reson. Chem. 38: 452-458.

Zangger, K., Oz, G., Otvos, J.D., Armitage, I.M. (1999) Three-dimensional solution structure of mouse [Cd7]-metallothionein-1 by homonuclear and heteronuclear NMR spectroscopy. Protein Sci. 8(12):2630-8. PubMed

A postdoctoral opening is anticipated for someone to use NMR & other biophysical methods for the structural characterization of a multiprotein complex found associated with metallothionein 3 in brain tissue. Available NMR instrumentation includes: 1 x 500, 2 x 600, and 1 x 800 MHz with cyroprobe Varian NMR spectrometers (http://www1.umn.edu/nmr) and mass spectrometry (http://biosci.cbs.umn.edu/mass_spec/).

Candidates with a strong background in NMR are encouraged to apply. The studies will provide an opportunity to gain experience in a broad range of methods which includes NMR, mass spectrometry, immunological techniques as well as techniques in protein expression/purification. Experience with computational methods will be given special consideration. The position is anticipated to be available mid tolate in 2005, the salary will be competitive and commensurate with experience with a term of 2-3 years.

Interested candidates should submit their curriculum vitae and letter outlining the expertise they feel they would bring to this new area of structural investigation. Letters of reference will be requested following the favorable review of this submitted material.

Professor Ian M. Armitage
Department of Biochemistry, Molecular Biology and Biophysics
University of Minnesota
6-155 Jackson Hall
321 Church Street S.E.
Minneapolis, MN 55455