Progress 07/01/08 to 06/30/13
Outputs
OUTPUTS: In the past year, our research has had several outputs. 1. It has trained three postdoctoral fellows, seven graduate students, seven undergraduate students, one high school student, and three elementary school teachers. This training includes both scientific and professional development. 2. We organized a symposium at the Annual Meeting of the American Society for Microbiology in San Diego, CA. 3. We developed a range of science outreach materials that were integrated into 20 after school programs for K-2 students in the Madison Metropolitan School District. 4. We hosted several science outreach events in our lab for elementary school students. 5. It led to several new collaborations with scientists across the world, including: Prof. Piotr Garstecki, Polish Academy of Sciences (Warsaw, Poland); Prof. KC Huang, Stanford University; Prof. Shoji Takeuchi, University of Tokyo. 6. We provided opportunities for cultural exchange by hosting one postdoctoral fellow from the University of Tokyo; one visiting graduate student from the Ecole Normale Superieure (Paris, France); and two graduate students from the Polish Academy of Sciences (Warsaw, Poland). PARTICIPANTS: Postdoctoral fellow: Shane Flickinger, PhD; Vladimir Smeianov, PhD; Lars Renner, PhD; Graduate students: Marie Foss, Matt Copeland, Hannah Tuson, Jack Ho, Jenna Eun, George Auer, Purba Mukerjee, Manohary Rajendram, Undergraduate students: Alex Stehle, Kelsey Thornton, Kelsey McLimans, Ryan Sacotte, Anyi Wang, Sonia Trevino; Dopatka High school students: John Ntambi, Elementary school teachers: Portia Meyer, Troy Dassler, Wendy Zucker; Projects provided opportunities for personal, professional, and scientific development. They also provided opportunities for science outreach with the general public. TARGET AUDIENCES: Faculty, postdoctoral fellows, graduate students, undergraduate students, K-12 students, parents, families, and teachers. A focus of our science outreach activities is to improve education among underrepresented minorities. PROJECT MODIFICATIONS: No major changes occurred in the 2010.
Impacts
We made several important breakthroughs in the past year, including the development of new antibiotics and the mechanisms that bacteria use to attenuate their pathogenicity. Perhaps the most important is the characterization of how membrane curvature in bacteria controls the spatial organization of lipids and regulates the localization of proteins in bacteria. This finding is the basis for a new hypothesis for how bacteria control their subcellular organization.
Publications
- 1. Foss, M.H.; Hurley, K.A.; Lackner, L.L.; Sorto, N.; Thornton, K.; Shaw, J.T.; Weibel , D.B. (2010) N-benzyl-3-sulfonamidopyrrolidines are a new class of bacterial DNA gyrase inhibitors. Submitted.
- 2. Renner, L.D.; Weibel, D.B. (2010) Physicochemical regulation of biofilm formation. Submitted.
- 3. Flickinger, S.T.; Copeland, M.F.; Downes, E.M.; Braasch, A.T.; Tuson, H. H.; Eun, Y.J.; Weibel, D.B. (2010) Chemical signaling between Pseudomonas aeruginosa communities accelerates biofilm development. Submitted.
- 4. Renner, L.D.; Weibel, D.B. (2010) Cardiolipin microdomains localize to negatively curved regions of Escherichia coli membranes. Proc. Natl. Acad. Sci. USA. In press.
- 5. Eun, Y.J.; Utada, A.S.; Copeland, M.F.; Takeuchi, S.; Weibel, D.B. (2010) High throughput amplification and analysis of bacteria in picoliter hydrogel particles. ACS Chem. Biol. In press.
- 6. Foss, M.H.; Weibel, D.B. (2010) Oligochlorophens are potent inhibitors of Bacillus anthracis. Antimicrob. Agents Chemother. 54, 3988-3990.
- 7. Copeland, M.F.; Flickinger, S.T.; Tuson, H.H.; Weibel, D.B. (2010) Studying the dynamics of flagella in multicellular communities of Escherichia coli by using biarsenical dyes. Appl. Environ. Microbiol. 76, 1241-1250.
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Progress 01/01/09 to 12/31/09
Outputs
OUTPUTS: A unique interweaving of chemistry, biology, and engineering underpins our efforts at Wisconsin. In essence, we are investigating how bacteria sense and respond to their environment and how these interactions reprogram the physiology and behavior of cells. One half of this research program studies multicellular behavior in bacteria. We use our background at the interface of chemistry and biology to study how the chemical and mechanical properties of surfaces play a role in the differentiation and growth of bacterial cells into communities that display multicellular behavior. Specifically, our group uses a combination of physical and genetic techniques to understand how cells sense surfaces and reprogram their behavior to make collective decisions about growth and motility that leads to pathogenesis and biofilm formation. Here, the approach involves reducing culture media to its most fundamental components--nutrients and a surface on which cells replicate--and changing the physical and chemical properties of the surface systematically so as to study quantitatively the fundamental basis for differentiation and growth. To do so, we synthesize hydrogels with specific surface chemistry and physical properties (e.g., elastic modulus, porosity, and surface structures) and measuring the rate of cellular growth and differentiation on these polymers. This work could lead to a new level of understanding (and control) of microbial life cycles. The other half studies the spatial and temporal organization of proteins and nucleic acid in bacteria. This research combines the development of several new techniques. For example, our group has developed a method for "molding" bacterial cells into novel shapes. These shapes are maintained after removal of the mold, indicating that the technique controls the orientation of peptidoglycan synthesis in the cell wall. We are using this approach to study how the intracellular organization of proteins determines bacterial shape and how shape may control the localization of polar proteins. This aspect of the research also draws upon his expertise in organic chemistry, as we have developed a high throughput screen to identify new cytoskeletal elements in bacterial cells and plans to discover small molecule inhibitors against these proteins. This multidisciplinary project is likely to yield new insights into microbial physiology and its control. PARTICIPANTS: Matt Copeland, Hannah Tuson, Jenna Eun, Marie Foss, Vladimir Smeianov, Shane Flickinger, Sonia Trevino-Dopatka, Sean McMaster; Students and postdocs in our lab have ample experience for professional development, including: attending conferences annually, presenting seminars on campus, interacting with collaborators and their students, and traveling to and working in the labs of both domestic and foreign collaborators. Students and postdocs also have the opportunity to attend workshops and courses for further professional development. TARGET AUDIENCES: The target audience is the entire population of Wisconsin. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
The results of our research have led to new antibiotics and the discovery of mechanisms that cells and multicellular structures of bacteria use to control their subcellular and multicellular organization.
Publications
- Copeland, M.F.; Weibel, D.B. (2009) Bacterial Swarming: A Model System for Studying Dynamic Self-Assembly. Soft Matter 5, 1174-1187.
- Moralimohan, A.; Eun, Y.J. Bhattacharyya, B.; Weibel, D.B. (2009) Dissecting Bacteria Using Materials Science. Trends Microbiol. 17, 100-108.
- Cabeen, M.T.; Charbon, G.; Vollmer, W.; Born, P.; Ausmees, N.; Weibel, D.B.; Jacobs-Wagner, C. (2009) Bacterial Cell Curvature via Mechanical Control of Cell Growth. EMBO J. 28, 1208-1219.
- Weibel, D.B. (2008) Building Communities One Bacterium at a Time. Proc. Natl. Acad. Sci. USA 99, 18075-18076.
- Copeland, M.F.; Flickinger, S.T.; Tuson, H.C.; Weibel, D.B. (2009) Studying the Dynamics of Flagella in Multicellular Communities of Escherichia coli Using Biarsenical Dyes. In press.
- Bean, G.J.; Flickinger, S.; McCully, M.; Westler, W.M.; Sept, D.; Weibel, D.B.; Amann, K.J. (2009) A22 Disrupts the Bacterial Actin Cytoskeleton by Directly Binding and Inducing a Low-Affinity State in MreB. Biochemistry 48, 4852-4857.
- Garstecki, P.; Tierno, P.; Weibel, D.B.; Sagues, F.; Whitesides, G.M. (2009) Propulsion of Flexible Polymer Structures in a Rotating Magnetic Field. J. Phys.: Condens. Matter 21, 204107.
- Eun, Y.J.; Weibel, D.B. (2009) Fabrication of Biofilm Arrays by Geometric Control of Cell Adhesion. Langmuir 25, 4643-4654.
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