[ Research Interests ] [ Representative Publications ]

Ludwig Brand Professor Department of Biology A.B. Harvard University Ph.D. Indiana University Postdoctoral Brandeis University Weizmann Institute

Department of Biology Johns Hopkins University 3400 North Charles Street Baltimore, MD 21218-2685 U.S.A. Office Telephone: Lab Telephone: Department Fax: Email: 410.516.7298 410.516.7300 410.516.5213 ludwig.brand@jhu.edu Office- Mudd 103D Lab- Mudd 103

Research Interests Conformation and Activity of Biological Macromolecules with Emphasis on Applications of Fluorescence Techniques The interest of our laboratory is to understand the static and dynamic structure of proteins, biological membranes, and nucleic acids. We are investigating motions of biological macromolecules that occur on time scales ranging from picoseconds to minutes. The work includes studies of the interactions between macromolecules and the relation between structure and function. Our research emphasizes the application of spectroscopy especially the use of steady-state and picosecond time-dependent fluorescence techniques. Fluorescence provides a relatively non-invasive probe whose power lies in its ability to examine intact, functional macromolecular assemblies. This type of spectroscopy is also applicable to studies of the intact cell. A variety of excited-state processes such as proton transfer, energy transfer, exciplex and excimer formation and solvent relaxation are being investigated so that these processes can be better used to study biological macromolecules in vivo and in vitro. These studies are done with intrinsic fluorophores such as the aromatic amino acids, the pyridine nucleotide co-enzymes, flavins, and pyridoxal. Related studies are done with a variety of extrinsic probes, some of which are specifically synthesized in the laboratory. Laser-based pulse and phase/modulation methods are utilized for the time-resolved fluorescence studies. Spectroscopic and other methods are used to study the galactose repressor and its interaction with galactose and other sugars. Oligonucleotides are lableled with fluorescence probes and fluorescence anisotropy and resonance energy transfer are used to study the interaction between the oligo and the galactose repressor. The aim of these studies is to better understand the statics and dynamics of the interaction between a repressor protein and DNA and allosteric effectors and thus to better understand the control of transcription. In collaboration with Professor Y.C. Lee we utilize steady-state and picosecond time-resolved fluorescence methods to study the conformations of complex carbohydrates and the interaction of carbohydrates with proteins. In collaboration with Professor Saul Roseman we use fluorescence and other biophysical methods to study the interaction of the protein and small molecule components involved in the phosphoenolpyruvate phosphotransferase system. It is of interest to understand the way in which phosphate is transferred from protein to protein and to learn more about the mechanisms involved in the control of the PTS in cells. We are involved in a study of conformational changes in interleukin-2, a cytokine. The fluorescence characteristics of this protein are unusual and probably involve an atypical hydrogen bond. We are interested in the monomer/dimer transition of this protein and how this is related to conformation and to aggregation. Representative Publications Xu J, Toptygin D, Graver KJ, Albertini RA, Savtchenko RS, Meadow ND, Roseman S, Callis PR, Brand L, Knutson JR. (2006). Ultrafast fluorescence dynamics of tryptophan in the proteins monellin and IIAGlc. J Am Chem Soc. 128(4):1214-21. Zheng Y, Mamdani F, Toptygin D, Brand L, Stivers JT, Cole PA. (2005). Fluorescence analysis of a dynamic loop in the PCAF/GCN5 histone acetyltransferase. Biochemistry. 44(31):10501-9. Toptygin, D., Savichenko, R.S., Meadow, N.D., Roseman S. and Brand, L.(2002). Effect of the solvent refractive index on the excited-state lifetime of a single tryptophan residue in a protein. Biophysics. J. 82: 425A Toptygin, D., Savichenko, R.S., Meadow, N.D. and Brand, L.  (2001). Homogeneous Spectrally and time-resolved fluorescence Emission from Single-Tryptophan of IIAGlc Protein. Journal of  Physical Chemistry B, 105, 2043-2055 . Nanda, V. and Brand, L. (2000) "Aromatic Interactions in Homeodomains Contribute to the Low Quantum Yield of a Conserved, Buried Tryptophan" PROTEINS, Structure, Function and Genetics, 40, 1121-125 Toptygin, D.and Brand, L., (2000)"Spectrally and Time-Resolved Fluorescence Emission of Indole During Solvent Relaxation: A Quantitative Model. Chem. Phys. Lett. 322, 496-502 Ya. K. Reshetnyak , O. A. Andreev , J. Borejdo, D. D. Toptygin, L. Brand and E. A. Burstein (2000)"The Identification of Tryptophan Residues Responsible for ATP-induced Increase in Intrinsic Fluorescence of Myosin Subfragment 1", Journal of Biomolecular Structure and Dynamics. 18, 113-125 Nanda, V., Liang, S-M. and Brand. L. (2000).Hydrophobic clustering in acid-denatured IL-2 and fluorescence of a Trp NH...p H bond.  Biochemical and Biophysical Research Communications 279, 770-778.

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3400 N. Charles St.
Baltimore, MD 21218

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