Our research program blends physical chemistry, biophysics, and chemical biology with disciplines such as microbiology to dissect the fundamental molecular and structural basis of macromolecular interactions in intact cells and other heterogeneous systems. We employ a diverse panel of biophysical and biochemical tools (and are designing new quantitative strategies using solid-state NMR spectroscopy) to profile chemical composition and to map structural contacts in assemblies such as amyloid fibers, bacterial biofilms, bacterial and plant cell walls, and biomass, in general.

Central goals in the group aim to understand: (i) how bacteria self-assemble fascinating extracellular structures, including functional amyloid fibers termed curli; (ii) how these structures mediate adhesion; and (iii) how bacteria use these and other building blocks to construct 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 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.

1. "Microbial Adhesion," L. Cegelski, C.L. Smith, and S.J. Hultgren, Encyclopedia of Microbiology (ed. M. Schaechter), 1-10 (2009)

2. "The Biology and Future Prospects of Antivirulence Therapies," L. Cegelski, G.R. Marshall, G.R. Eldridge, and S.J. Hultgren, Nature Reviews Microbiology, 6, 17-27 (2008).

3. "Morphological Plasticity as a Bacterial Survival Strategy," S.S. Justice, D.A. Hunstad, L. Cegelski, and S.J. Hultgren, Nature Reviews Microbiology, 6, 162-168 (2008).

4. "Oritavancin Exhibits Dual Mode of Action to Inhibit S. aureus Peptidoglycan Biosynthesis," S.J. Kim, L. Cegelski, D. Stueber, M. Singh, E. Dietrich, K.S. Tanaka, T.R. Parr, A.R. Farand, and J. Schaefer, Journal of Molecular Biology, 377, 281-293 (2008)

5. "Conformational and Quantitative Characterization of Oritavancin-Peptidoglycan Complexes in Whole Ceells of Staphylococcus aureus by in vivo 13Cand 15N Labeling," L. Cegelski, D. Steuber, A.K. Mehta, D.W. Kulp, P.H. Axelsen, and J. Schaefer, Journal of Molecular Biology, 357, 1253-62 (2006).

6. "Peptide Antibiotics in Action: Investigation of Polypeptide Chains in Insoluble Environments by REDOR," O. Toke, L. Cegelski, and J. Schaefer, Review: Biochimica et Biophysica Acta, 1758, 1314-1329 (2006).