Microbial Biochemistry and Engineering
We study concepts of biological organization across length scales in microorganisms. Our research focuses on decoding mechanisms that regulate organization in microbiological systems and redesigning and exploiting these interactions and machinery to engineer new function into cells and communities. The long-term goal of this research is two-fold: (1) to use our understanding of these systems to design mechanisms for controlling bacterial behavior and pathogenesis; (2) to build new materials and structures out of microbial cells and their communities. Bacterial display a remarkable degree of complexity across a wide range of length scales and our understanding of this area of science is just beginning to emerge.
At the nanometer scale, proteins assemble into dynamics polymers in vivo that control fundamental physiological processes in bacteria, including: growth, division, and cell morphology. The anisotropy and dynamics of lipids in the cell membrane appears to play a role in the spatial organization of proteins in bacteria that are important to cell physiology and behavior. An understanding of these mechanisms may be an important step forward in the development of the next generation of antibiotics that bolster our dwindling number of effective antimicrobial drugs. As some of these processes and proteins have homologous counterparts in eukaryotes (e.g. mammalian cells), studying these components in bacteria may be advantageous, as cell growth is rapid, molecular genetics is straightforward, genome-wide libraries of mutants and chimeras are available, and biochemistry is well-studied. Our approach to this area combines chemical biology to control the function of proteins in vivo using small molecules with biophysical experiments and modeling.
At the micrometer scale, cells interact with other cells and with their environment through processes that are controlled by molecular contact, diffusion, and mass transport, which regulates their growth and behavior. Chemical communication is important at this length scale, as are physical interactions, which include, cell/cell, cell/surface, and cell/fluid interactions. An understanding of these processes may illuminate the phenotypes and behavior of bacteria in their natural environment and may play a role in growing, isolating, and studying previously uncultivated bacteria. Our approach to this area combines materials science and engineering to make microstructures with physical chemistry and biophysics to study physical interactions between bacterial cells and their environment.
At the mesoscale (millimeters to centimeters), microbial cells assemble into communities that are prevalent in ecology and human health. These structures include fruiting bodies, mycelia, colonies, swarms, and biofilms. The organization and dynamics of these structures is fascinating. The mechanisms that coordinate the behavior, physiology, and assembly of cells into dynamic communities will shed light on the structure and function of communities in hosts (e.g. Escherichia coli in the human gut). An understanding of the coupling between the coordination of microscopic motion and large-scale pattern formation and organization across entire communities may play a role in understanding mechanisms that drive systems toward 'emergence' and illuminate systems that are far from microbiology, including: weather, financial markets, and traffic. Our research in this area uses a wide-collection of experimental approaches to understand spatial and temporal dynamics of cells in communities that emerge in 'native habitats' that we fabricate in the lab.
To carry out this research we fuse techniques from the biological sciences, physical sciences, and engineering. Using a multidisciplinary approach provides us with the broadest possible selection of tools and capabilities for studying microbiological systems. Combining the techniques and mindset from different areas of science and engineering often provides surprises and new insights into biological questions. This approach provides a valuable opportunity for the scientific development of students, who interact and work closely with faculty and students from areas of science outside of their expertise. Students who train in our lab leave with a broad view of science and excellent problem solving skills.
Our research is also having an impact on local science education. By combining our interest in educational outreach with the strong culture of outreach at UW-Madison, we are developing programs and participating in opportunities on campus that introduce scientific concepts to children, adults, teachers, and families in the Madison Metropolitan School District. The MicroExplorers program is an excellent example of our efforts to improve local science education; for updates visit the MicroExplorers blog.