个人简介

Lynette Cegelski Assistant Professor Education: B.S., 1998, Binghamton University, SUNY; Ph.D., 2004, Washington University Awards: Burroughs Wellcome Fund Career Award at the Scientific Interface Terman Fellowship, 2008 NIH Director's New Innovator Award, 2010 Hellman Faculty Scholar, 2012

研究领域

Biophysical/Chemical Biology/Physical

Our research program integrates chemistry, biology, and physics to investigate the assembly and function of macromolecular and whole-cell systems. The genomics and proteomics revolutions have been enormously successful in generating crucial "parts lists" for biological systems. Yet, for many fascinating systems, formidable challenges exist in building complete descriptions of how the parts function and assemble into macromolecular complexes and whole-cell factories. We are inspired by the need for new and unconventional approaches to solve these outstanding problems. Our approach is different from the more conventional protein-structure determinations of structural biology. We employ biophysical and biochemical tools, and are designing new strategies using solid-state NMR spectroscopy to examine assemblies such as amyloid fibers, bacterial cell walls and biofilms, and biomass, in general. We would like to understand at a molecular and atomic level how bacteria self-assemble extracellular structures, including functional amyloid fibers termed curli, and how bacteria use curli and other building blocks to construct organized biofilm architectures. The curli system itself is especially notable as a coordinated, multi-protein amyloid cascade. New discoveries in curli biogenesis may provide insight into the alternative folding and mis-assembly of proteins associated with human amyloid diseases. We are working to define the macromolecular interactions during curli assembly as well as biofilm formation, and to examine the influence of environmental stimuli, such as small-molecule signals and inhibitors. In this effort, our group is also employing a chemical genetics approach to recruit small molecules as tools to interrupt and interrogate the temporal and spatial events during assembly processes. Overall, our approach is multi-pronged and provides training opportunities for physical, biophysical, and biological chemistry students interested in research at the chemistry-biology interface.

近期论文

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Spectral Snapshots of Bacterial Cell-Wall Composition and the Influence of Antibiotics by Whole-Cell NMR. Nygaard R, Romaniuk JAH, Rice DM, Cegelski L. Biophysical Journal (2015) Accepted. Bottom-Up and Top-Down Solid-State NMR Approaches for Bacterial Biofilm Matrix Composition. Cegelski L. Journal of Magnetic Resonance (2015) Accepted. Characterization of the Vibrio cholerae Extracellular Matrix: A Top-Down Solid-State NMR Approach. Reichhardt C, Fong JCN, Yildiz F, Cegelski L. Biochimica et Biophysica Acta - Special Issue on "NMR Spectroscopy for Atomistic Views of Biomembranes and Cell Surfaces" (2015) 1848, 378-383. - Editorial (Cegelski & Weliky) - Special Issue Table of Contents. Molecular Determinants of Mechanical Properties of V. cholerae Biofilms at the Air-Liquid Interface. Hollenbeck E, Fong JCN, Lim JY, Yildiz F, Fuller GG, Cegelski L. From the cover. Biophysical Journal (2014) 107, 2245-2252. - Cover image Putative Hydrogen Bond to Tyrosine M208 in Photosynthetic Reaction Centers from Rhodobacter capsulatus Significantly Slows Primary Charge Separation. Saggu M, Carter B, Zhou X, Faries K, Cegelski L, Holten D, Boxer SG, Kirmaier C. Journal of Physical Chemistry B (2014) 118, 6721-6732. Solid-State NMR for Bacterial Biofilms. Reichhardt C and Cegelski L. From the cover. Molecular Physics (2014) 112, 887-894. - Cegelski Author Profile - Cover image Community Behavior and Amyloid-associated Phenotypes among a Panel of Uropathogenic E. coli. Lim JY, Pinkner JS, Cegelski L. Biochemical and Biophysical Research Communications (2014) 443, 345-350. REDOR NMR for Drug Discovery. Cegelski L. Bioorganic & Medicinal Chemistry Letters (2013) 23, 5767-5775. Dedicated to Prof. Jacob Schaefer in celebration of his 75th Birthday and 25 years of REDOR. Sum of the Parts: Composition and Architecture of the Bacterial Extracellular Matrix. McCrate O, Zhou X, Reichhardt C, Cegelski L. Journal of Molecular Biology (2013). Disruption of E. coli Amyloid-Integrated Biofilm Formation at the Air-Liquid Interface by a Polysorbate Surfactant. Wu C, Lim JY, Fuller GG, Cegelski L. Langmuir (2013) 29, 920–926. Curcumin as an Amyloid-Indicator Dye in E. coli. McCrate OA, Zhou X, Cegelski L. Chemical Communications (2013) 49, 4193-4195. Nutrient-Dependent Structural Changes in S. aureus Peptidoglycan Revealed by Solid-State NMR Spectroscopy. Zhou X and Cegelski L. Biochemistry (2012) 51, 8143-8154. - Press Highlight Quantitative Analysis of Amyloid-Integrated Biofilms Formed by Uropathogenic E. coli at the Air-Liquid Interface. Wu C, Lim JY, Fuller GG, Cegelski L. Biophysical Journal (2012) 103, 464-471. DMSO and Ethanol Elicit Increased Amyloid Biogenesis and Amyloid-Integrated Biofilm Formation in E. coli. Lim JY, May JM, Cegelski L. Journal of Applied and Environmental Microbiology (2012) 78, 3369-3378. REDOR Applications in Biology: an Overview. Toke O and Cegelski L. In Solid-State NMR Studies of Biopolymers (2010). McDermott, AE and Polenova, T (eds). John Wiley & Sons Ltd, Chichester, UK, pp 473-490. Plant Cell-Wall Cross-s by REDOR NMR Spectroscopy. Cegelski L, O’Connor RD, Stueber D, Singh M, Poliks B, Schaefer J. Journal of the American Chemical Society (2010) 132:16052-7. Small-Molecule Inhibitors Target E. coli Amyloid Biogenesis and Biofilm Formation. Cegelski L, Pinkner JS, Hammer ND, Cusumano CK, Hung CS, Chorell E, Åberg V, Walker JN, Seed PC, Almqvist F, Chapman MR, Hultgren SJ. Nature Chemical Biology (2009) 5, 913-919. Microbial Adhesion. Cegelski L, Smith CL, Hultgren SJ. In The Encyclopedia of Microbiology, ed. Schaechter, M. (2009), 1-10. Morphological Plasticity as a Bacterial Survival Strategy. Justice SJ, Hunstad DH, Cegelski L, Hultgren SJ. Nature Reviews Microbiology (2008) 6, 162-168. The Biology and Future Prospects of Anti-Virulence Therapies. Cegelski L, Marshall GR, Eldridge GR, Hultgren SJ. Nature Reviews Microbiology (2008) 6, 17-27.