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Seminar: Allison Williams PhD (Institut Pasteur, Paris)

June 25, 2019 @ 11:00 am - 12:00 pm


“The Cryo-Electron Microscopy Supramolecular structure of the Bacterial Stressome Unveils Its Mechanism of Activation”

Allison Williams

Institut Pasteur, Paris


For more than a decade I have been exploring the mechanistic and functional role of essential enzymes involved in bacterial cell wall biosynthesis. In the laboratory of Professor Christian R.H. Raetz (Duke University), I studied the mechanism of enzymes involved in lipid A assembly and explored their potential as possible antimicrobial targets using primarily X-ray crystallography. This work implemented new methodology for studying the structural and molecular details of these enzymes combined with their complex lipid derived substrates or products. Specifically, I was able to reveal the mechanism and substrate specificities of UDP-N-acetylglucosamine (UDP-GlcNAc) acyltransferase (LpxA) the first enzyme in the lipid A biosynthesis pathway. These approaches resulted in the design and discovery of potent inhibitors that target LpxA. Within the last 6 years, I implemented innovative approaches to structurally visualize snapshots of enzymes involved in peptidoglycan metabolism using active enzymes in the crystalline state. So far, we have been able to elucidate the mechanism and substrate specificities of at least three peptidoglycan modifying enzyme.

More recently my research program has been focused on structurally uncharacterized protein machines that are crucial to bacterial physiology; specifically, those involved in the cell wall biogenesis or in the activation of survival mechanisms to overcome environmental stresses. It is known that the synthesis of peptidoglycan the major polymeric component of the cell wall, is executed via a machinery consisting of multiple interacting proteins, however, there is a paucity of structural characterization and functional information about these complexes. Similarly, the activation of the bacterial stress response is executed by large nanomachines, however, atomic resolution structures or their mechanism of activation remains elusive, limiting our complete understanding of their mechanism of action. My study employs a multi-disciplinary approach that combines, X-ray crystallography, cryo-electron microscopy (cryo-EM) single molecule reconstruction, with biochemical, genetic, and in vivo studies. So far, we have elucidated the underlying mechanisms used by bacterial nanomachines to facilitate environmental adaptation and bacterial survival under stress. I already have exciting preliminary data, supporting our hypothesis that, exploring these protein assemblies or nanomachineries could be highly relevant for the development of the next generation of antimicrobial agents that disrupt bacterial cell wall machineries, as well as disable the ability of the bacteria to adapt to or activate various stress responses.

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June 25, 2019
11:00 am - 12:00 pm
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Marsico 7004
125 Mason Farm Rd
Chapel Hill, NC 27599


Lisa Phillippie
(919) 843-9737