个人简介

B.A., 1985, Swarthmore College Ph.D., 1995, Univ. of Chicago Postdoctoral Fellow, 1995-97, National Institutes of Health. AwardOrganizationDivisionLevel CodeType CodeStart DateEnd Date New Faculty AwardCamille and Henry Dreyfus FoundationProfessionalHonors1998 NIH Fellows Award for Research ExcellenceNational Institutes of HealthPostdoctoralHonors1996 Postdoctoral Research FellowNational Institutes of HealthPostdoctoralFellowship19951997 Ph.D.The University of ChicagoGraduateDegree1995 Research FellowAT&T Bell LaboratoriesGraduateFellowship1992 AT&T Ph.D. ScholarAT&TGraduateHonors19911995 NSF Predoctoral FellowNational Science FoundationGraduateFellowship19881991 McCormick FellowGraduateFellowship19871991 Bachelor of Arts with High Honors in Chemistry and PhysicsSwarthmore CollegeUndergraduateDegree1985 Phi Beta KappaPhi Beta KappaSwarthmore CollegeUndergraduateHonors1985 MemberSigma Xi Honor SocietySwarthmore CollegeUndergraduateHonors1985 N. Harvey Collisson ScholarSwarthmore CollegeUndergraduateHonors19811982 National Merit ScholarUndergraduateHonors19811985

研究领域

Analytical Biological Chemical Physics Inorganic Materials Physical

(Research Description PDF - 1037 kb) Nuclear magnetic resonance (NMR) spectroscopy in the solid state is a powerful approach to determine atomic-resolution structure and motion in systems for which the molecules do not rapidly tumble. Our research focuses on application of solid-state NMR to problems in membrane fusion, bacterial inclusion bodies, and inorganic materials. Membrane Fusion: Fusion between cells and cellular components has an essential role in living organisms for such significant physiological processes as egg fertilization and synaptic transmission in the nervous system. Membrane fusion is also an important step in HIV and influenza viral infection of human cells and is mediated by proteins in the viral membrane that bind to the target cell membrane during infection. We are using solid-state NMR to determine the conformations, membrane locations, and oligomerization states of the membrane-bound HIV and influenza viral fusion proteins and using these data to develop an atomic-resolution structural model of fusion protein-induced membrane fusion. (Top) Normal E. coli cell. (Bottom) E. coli cell that has produced recombinant protein. The dark regions in the right panel are inclusion bodies. Bacterial Inclusion Bodies: Proteins for fundamental research or therapeutic purposes are usually produced by putting the DNA which codes for the protein into E. coli bacteria, culturing the bacteria to high densities, and then inducing production of the “recombinant” protein. Most of the recombinant protein is usually sequestered in non-crystalline solids in the bacterial cytoplasm that are termed “inclusion bodies” and which are viewed negatively by researchers because typical solubilization protocols for inclusion bodies are denaturing with the subsequent requirement of refolding whose success is variable and dependent on the specific protein. Because there is little molecular-level structural information on inclusion body protein, we are carrying out solid-state NMR studies with a particular emphasis on inclusion bodies in whole bacterial cells. One overall goal is development of non-denaturing solubilization protocols for inclusion body protein. While doing this research, students learn a variety of skills which could include peptide synthesis, protein expression and purification, design and repair of NMR equipment, NMR theory and pulse sequence development, and computer simulation. Our research is benefiting from the enhanced sensitivity and resolution of the 900 MHz NMR spectrometer at MSU.

近期论文

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L. Jia, S. Liang, K. Sackett, L. Xie, U. Ghosh, and D. P. Weliky, "REDOR Solid-State NMR as a Probe of the Membrane Locations of Membrane-Associated Peptides and Proteins", Journal of Magnetic Resonance, 253, 154-165 (2015). L. Xie, L. Jia, S. Liang, and D. P. Weliky, "Multiple Locations of Peptides in the Hydrocarbon Core of Gel-Phase Membranes Revealed by Peptide 13C to Lipid 2H Rotational-Echo Double Resonance Solid-State Nuclear Magnetic Resonance", Biochemistry, 54, 677-684 (2015) – highlighted on Biochemistry website. P. Ratnayake, K. Sackett, M. J. Nethercott, and D. P. Weliky, "pH-Dependent Vesicle Fusion Induced by the Ectodomain of the Human Immunodeficiency Virus Membrane Fusion Protein gp41: Two Kinetically Distinct Processes and Fully-Membrane-Associated gp41 with Predominant β sheet Fusion Peptide Conformation", Biochimica et Biophysica Acta, 1848, 289-298 (2015). L. Cegelski and D. P. Weliky, "NMR Spectroscopy for Atomistic Views of Biomembranes and Cell Surfaces", Biochimica et Biophysica Acta, 1848, 201-202 (2015). K. Banerjee and D. P. Weliky, "Folded Monomers and Hexamers of the Ectodomain of the HIV gp41 Membrane Fusion Protein: Potential Roles in Fusion and Synergy Between the Fusion Peptide, Hairpin, and Membrane-Proximal External Region", Biochemistry, 53, 7184-7198 (2014). K. Sackett, M. J. Nethercott, Z. Zheng, and D. P. Weliky, "Solid-State NMR Spectroscopy of the HIV gp41 Membrane Fusion Protein Supports Intermolecular Antiparallel b Sheet Fusion Peptide Structure in the Final Six-Helix Bundle State", Journal of Molecular Biology, 426, 1077-1094 (2014). C. M. Gabrys, W. Qiang, Y. Sun, L. Xie, S. D. Schmick, and D. P. Weliky, "Solid-State Nuclear Magnetic Resonance Measurements of HIV Fusion Peptide to Lipid 31P Proximities Support Similar Partially Inserted Membrane Locations of the a Helical and b Sheet Peptide Structures", Journal of Physical Chemistry A, 117, 9848-9859 (2013). E. P. Vogel and D. P. Weliky, "Quantitation of Recombinant Protein in Whole Cells and Cell Extracts via Solid-State NMR Spectroscopy", Biochemistry, 52, 4285-4287 (2013) – highlighted on Biochemistry website. U. Ghosh, L. Xie, and D. P. Weliky, "Detection of Closed Influenza Virus Hemagglutinin Fusion Peptide Structures in Membranes by Backbone 13CO-15N Rotational-Echo Double-Resonance Solid-State NMR", Journal of Biomolecular NMR, 55, 139-146 (2013). L. Xie, U. Ghosh, S. D. Schmick, and D. P. Weliky, "Residue-Specific Membrane Location of Peptides and Proteins Using Specifically and Extensively Deuterated Lipids and 13C-2H Rotational-Echo Double-Resonance Solid-State NMR", Journal of Biomolecular NMR, 55, 11-17 (2013). E. P. Vogel, J. Curtis-Fisk, K. M. Young, and D. P. Weliky, "Solid-State Nuclear Magnetic Resonance (NMR) Spectroscopy of Human Immunodeficiency Virus gp41 Protein that includes the Fusion Peptide: NMR Detection of Recombinant Fgp41 in Inclusion Bodies in Whole Bacterial Cells and NMR Structural Characterization of Purified and Membrane-Associated Fgp41", Biochemistry, 50, 10013-10026 (2011). K. Sackett, A. TerBush, and D. P. Weliky, "HIV Six-Helix Bundle Constructs Induce Rapid Vesicle Fusion at pH 3.5 and Little Fusion at pH 7.4: Understanding pH Dependence of Protein Aggregation, Membrane Binding, and Electrostatics, and Implications for HIV-Host Cell Fusion", European Biophysics Journal, 40, 489-502 (2011). S. D. Schmick and D. P. Weliky, "Major Antiparallel and Minor Parallel b Sheet Populations Detected in the Membrane-Associated Human Immunodeficiency Virus Fusion Peptide", Biochemistry, 49, 10623-10635 (2010). S. Tristram-Nagle, R. Chan, E. Kooijman, P. Uppamoochikkal, W. Qiang, D. P. Weliky, and J. F. Nagle, "HIV Fusion Peptide Penetrates, Disorders, and Softens T-cell Membrane Mimics", Journal of Molecular Biology, 402, 139-153 (2010). I. Chung, D. Holmes, D. P. Weliky, and M. G. Kanatzidis, "[P3Se7]3–: A Phosphorus-Rich Square-Ring Selenophosphate", Inorganic Chemistry, 49, 3092-3094 (2010). K. Sackett, M. J. Nethercott, R. F. Epand, R. M. Epand, D. R. Kindra, Y. Shai, and D. P. Weliky, "Comparative Analysis of Membrane-Associated Fusion Peptide Secondary Structure and Lipid Mixing Function of HIV gp41 Constructs that Model the Early Pre-Hairpin Intermediate and Final Hairpin Conformations", Journal of Molecular Biology, 397, 301-315 (2010). C. M. Gabrys, R. Yang, C. M. Wasniewski, J. Yang, C. G. Canlas, W. Qiang, Y. Sun, and D. P. Weliky, "Nuclear Magnetic Resonance Evidence for Retention of Lamellar Membrane Phase with Curvature in the Presence of Large Quantities of the HIV Fusion Peptide", Biochimica et Biophysica Acta, 1798, 194-201 (2010). N. Huarte, J. L. Nieva, S. Nir and D. P. Weliky, "Induced Perturbations and Adopted Conformations in Membranes by the HIV-1 Fusion Peptide", In Membrane-Active Peptides: Methods and Results on Structure and Function, M. A. R. B. Castanho, Editor, International University Line:La Jolla, 2009, pp. 565-596. I. Chung, J.-H. Song, M. G. Kim, C. D. Malliakas, A. L. Karst, A. J. Freeman, D. P. Weliky, and M. G. Kanatzidis, "The Tellurophosphate K4P8Te4: Phase-Change Properties, Exfoliation, Photoluminescence in Solution and Nanospheres", Journal of the American Chemical Society, 131, 16303-16312 (2009). Y. Sun and D. P. Weliky, "13C-13C Correlation Spectroscopy of Membrane-Associated Influenza Virus Fusion Peptide Strongly Supports a Helix-Turn-Helix Motif and Two Turn Conformations", Journal of the American Chemical Society, 131, 13228-13229 (2009).