Dr. Douglas B. Weibel, from the Departments of Biochemistry, Chemistry, and Biomedical Engineering of the University of Wisconsin -Madison will be offering a lecture titled “Mechanical Genomics: Genome-Wide Identification of Bacterial Cell Wall Stiffness”.
Date: March 6, 2014
Time: 10:30 am – 12:00 pm
Place: Abbott Room Chemistry Building
Abstract:
The peptidoglycan (PG) consists of a single, cross-linked layer of polysaccharide that forms the primary load-bearing material of bacteria and resists the large osmotic pressure across the cell wall. As defects in PG assembly and remodeling are catastrophic to cells, mechanistic studies in this area may lead to the discovery of new targets and antibiotics that inhibit cell wall assembly.
In the first part of my talk, I describe materials-based approach we have developed to measure the stiffness of the cell wall of growing bacteria. We refer to this technique as CLAMP: cell length analysis of mechanical properties, as it effectively describes a polymer clamp technique for determining the composite Young’s modulus of the cell wall (Ecell), which defines the intrinsic stiffness of materials. Importantly, Ecell can be translated into changes in PG mechanical properties and provide insight into several properties of this material, including: 1) its structure; 2) its conservation across bacteria; and 3) its response to chemical and biological perturbations.
In the second part of my talk I describe the application of a high-throughput variation of CLAMP to study mechanical genomics—that is, quantifying how genome-wide alterations influence cell mechanical properties. We have used CLAMP to screen an entire gene deletion library in Escherichia coli (~3700 mutants) and have correlated the loss of each gene with cell wall mechanical properties. This approach has enabled us to identify new machinery and regulators of PG and cell wall assembly and has yielded some very surprising results. I describe the results of these experiments and how it is shaping our view of the assembly, properties, and function of the cell wall, providing targets for antimicrobial chemotherapy, and introducing new classes of industrial biopolymers.
Organized by: Wi(PR)2EM