The Varga lab focuses on the biophysical characterization of protein structure and function. We use NMR and other spectroscopic techniques to investigate protein structure, protein-protein, and protein-ligand interactions. Another major research interest is the design and characterization of chiral nanoparticles. Ongoing projects include:
Antifreeze proteins are found in a wide range of cold adapted organisms, and they contribute to their freeze resistance. Antifreeze proteins adsorb to the ice surface and inhibit the growth of ice crystals. The goal of this project is to investigate the mechanism by which antifreeze proteins protect against the damage typically inflicted by cold, including the underlying molecular mechanism of ice-binding. This project is supported by NASA-EPSCoR and NIH.
Quantum dots (QDs) are nanometer size semiconductor crystals with excellent and tunable electronic and optical properties. Colloidal quantum dots consist of an inorganic semiconductor core (e.g. CdSe) and an organic capping ligand shell (e.g. cysteine). We aim to determine how chiral organic ligands induce chiroptical activity in achiral semiconductor QDs and how QDs can be used to enhance the chiroptical signal of biomolecules. Chiral QDs are promising candidates for bioimaging, biosensing, environmental nanoassays, catalysis, and chiral memory. his project was supported by NSF.
REGULATORS OF G-PROTEIN SIGNALING PROTEINS
The discoveries of a class of intracellular regulatory proteins known as regulators of G-protein signaling (RGS) proteins that mediate GPCR signaling via protein-protein interactions between the RGS domains and the gamma-subunit of G-proteins and their covalent inhibitors have opened a new venue for allosteric targeting in GPCRs. We are studying inhibitor-induced structural perturbations using NMR and MD analyses of the RGS8 protein and its mutant forms to understand the role of cysteine residues in affecting potency and specificity of inhibitors. This project is supported by NIH.
RATES OF PROTEIN EVOLUTION
We aim to identify the factors that have an important impact on the rates of protein evolution and elucidate the reasons why these factors affect rates of evolution. During evolution, different proteins accumulate amino acid changes at enormously different rates as a result of the different selective pressures to which they are subjected. This project is supported by NSF.
BACTERIAL MECHANISMS IN ESTABLISHING AND MAINTAINING CELL POLARITY
The polar organizing protein Z (PopZ) is necessary for the formation of three-dimensional microdomains at the cell poles in Caulobacter crescentus, where it functions as a hub protein that recruits multiple regulatory proteins from the cytoplasm. Although a large portion of the protein is predicted to be natively unstructured, in reconstituted systems PopZ can self-assemble into a macromolecular scaffold that directly binds to at least ten different proteins. We have utilized NMR spectroscopy to study its interaction with its binding partners. This project was supported by NIH.
Ph.D., Chemistry, Columbia University
M.S., Biology, St. John’s University
B.S., Chemistry, St. John’s University
BCHM 999: Doctoral Research
BCHM/BMCB 850/750: Physical Biochemistry
BCHM/BMCB 851/751: Principles of Biochemistry I
BMCB 658: General Biochemistry
BMCB 799H: Honors Senior Thesis
MCBS 901: Intro to Research in Life Sci
MCBS 999: Doctoral Thesis
MICR 999: Doctoral Research
Nordyke, C. T., Ahmed, Y. M., Puterbaugh, R. Z., Bowman, G. R., & Varga, K. (2020). Intrinsically Disordered Bacterial Polar Organizing Protein Z, PopZ, Interacts with Protein Binding Partners Through an N-terminal Molecular Recognition Feature. Journal of Molecular Biology, 432(23), 6092-6107. doi:10.1016/j.jmb.2020.09.020
Gupta, R., Liu, Y., Wang, H., Nordyke, C. T., Puterbaugh, R. Z., Cui, W., . . . Cote, R. H. (2020). Structural Analysis of the Regulatory GAF Domains of cGMP Phosphodiesterase Elucidates the Allosteric Communication Pathway. Journal of Molecular Biology, 432(21), 5765-5783. doi:10.1016/j.jmb.2020.08.026
Tannir, S., Levintov, L., Townley, M. A., Leonard, B. M., Kubelka, J., Vashisth, H., . . . Balaz, M. (2020). Functional Nanoassemblies with Mirror-Image Chiroptical Properties Templated by a Single Homochiral DNA Strand. Chemistry of Materials, 32(6), 2272-2281. doi:10.1021/acs.chemmater.9b04092
Kratochvílová, I., Kopečná, O., Bačíková, A., Pagáčová, E., Falková, I., Follett, S. E., . . . Falk, M. (2019). Changes in Cryopreserved Cell Nuclei Serve as Indicators of Processes during Freezing and Thawing. Langmuir, 35(23), 7496-7508. doi:10.1021/acs.langmuir.8b02742
Varga, K., Balaz, M., Joh, Y., Berova, N., Purrello, R., & D'Urso, A. (2019). Structure and Electronic Circular Dichroism of Chiral Porphyrins and Chiral Porphyrin Dimers. In K. Kadish, K. Smith, & R. Guilard (Eds.), Handbook of Porphyrin Science (Vol. 45, pp. 205-284).
Hagemann, N., Joseph, S., Schmidt, H. -P., Kammann, C. I., Harter, J., Borch, T., . . . Kappler, A. (2017). Organic coating on biochar explains its nutrient retention and stimulation of soil fertility. Nature Communications, 8(1). doi:10.1038/s41467-017-01123-0
Choi, J. K., Haynie, B. E., Tohgha, U., Pap, L., Elliott, K. W., Leonard, B. M., . . . Balaz, M. (2016). Chirality Inversion of CdSe and CdS Quantum Dots without Changing the Stereochemistry of the Capping Ligand. ACS Nano, 10(3), 3809-3815. doi:10.1021/acsnano.6b00567
Tohgha, U., Deol, K. K., Porter, A. G., Bartko, S. G., Choi, J. K., Leonard, B. M., . . . Balaz, M. (2013). Ligand Induced Circular Dichroism and Circularly Polarized Luminescence in CdSe Quantum Dots. ACS Nano, 7(12), 11094-11102. doi:10.1021/nn404832f
Tohgha, U., Varga, K., & Balaz, M. (2013). Achiral CdSe quantum dots exhibit optical activity in the visible region upon post-synthetic ligand exchange with d- or l-cysteine. Chemical Communications, 49(18), 1844. doi:10.1039/c3cc37987f
Warner, L. R., Varga, K., Lange, O. F., Baker, S. L., Baker, D., Sousa, M. C., & Pardi, A. (2011). Structure of the BamC Two-Domain Protein Obtained by Rosetta with a Limited NMR Data Set. Journal of Molecular Biology, 411(1), 83-95. doi:10.1016/j.jmb.2011.05.022