The investigator constructs mathematical models for bacterial propulsion and pattern formation. Attention is restricted mostly to two classes of bacteria: myxobacteria and mollicutes. This work is performed in collaboration or correspondence with experimental laboratories engaged in studies of these organisms. The models are primarily directed towards understanding and explaining their experimental observations. The specific goals of this project are to model (i) the gliding mechanisms of Myxobacteria and Mollicutes, (ii) the swimming mechanisms of E. coli and Synechococcus, and (iii) aggregation and fruiting body formation in Myxobacteria.
The investigator develops mathematical and computational models of different mechanisms by which bacteria move. Bacteria use many different mechanisms to move about on surfaces and through fluids. The term "gliding" is used to describe the motion of bacteria on surfaces when there is no visible means of propulsion. The investigator studies the molecular and cellular mechanisms that underlie this mysterious form of locomotion. Many bacteria swim, driven by rotating "propellors" called flagella. However, the motor mechanism that turns this propellor has not been worked out, and is a focus of this project. The photosynthetic bacterium, Synechococcus, lives in the oceans, and constitutes the most abundant organism on the planet. How it swims is a longstanding mystery, for it has no visible propulsive organelle on its surface. The investigator and his colleagues suggest and model a mechanism for how this bacterium swims. The broader impact of these studies grows from the insights they provide into the propulsion, development, and mechanochemistry of bacteria, many of which are important pathogens of great medical interest.
Of all the properties of cellular life, the most apparent is the ability to move—be it molecules or organelles within cells, or entire cells. The laws of physics requires that all motions be driven by mechanical forces. So understanding biological motion requires understanding how propulsive forces are generated from chemical energy, and how these forces are harnessed to produce movement. Addressing these questions is the goal of my research. The energy sources the cell uses to create forces arise from the attractive forces between molecules. These forces come in several flavors, some strong, others much weaker. 'Protein motors' carry out an enormous repertoire of tasks inside the cells, and they come in a plethora of different sizes and shapes. However all use only two sources of energy. One is energy stored in the universal fuel molecule—called ATP—and the other is the energy stored in the strong electric field cells maintains across their membrane separating its cytoplasm from the extracellular environment. In our work supported by this grant we have focussed our attention on motors that process DNA, either to unwind DNA, to produce a complementary RNA strand, or to package DNA into a viral capsid. The first study showed how a DNA 'helicase',—a motor with only one ATP binding site, a rarity amongst molecular motors—could nevertheless unwind the two strands of DNA prior to replication. [Yu, Jin, W. Cheng, C. Bustamante, G. Oster. (2010) Coupling Translocation with Nucleic Acid Unwinding by NS3 Helicase. J. Molec. Biol. 404:439-455.] The second study showed how a primitive virus motor could produce an RNA strand from an unwound DNA template with a very small error rate (mistakes in copying DNA to RNA generally have fatal consequences). [Yu, J., G. Oster. (2011) A small translocation energy bias aids in nucleotide selection in T7 RNA Polymerase transcription. (In Submission)] The third study produced a comprehensive mechanochemical model for the motor that packages DNA into the body of a virus. The model is able to fit quantitatively virtually all of the experimental data. We feel that this is a major step in understanding how DNA motors work, for many other motors appear to use the same physical and chemical machinery. [Yu, J., J. Moffitt, C. Hetherington, C. Bustamante, G. Oster.(2010) Mechanochemistry of the phi29 packaging motor. J. Molec. Biol. 400:186-203.] Three additional publications were completed under this 1-year extension. Drubin, D., G. Oster. (2010) Experimentalist Meets Theoretician: A Tale of Two Scientific Cultures. Molec. Biol. Cell 21: 2099–2101. This was an expository article describing the ups and downs of a productive collaboration between an experimental biologist and a theoretician. Nan, B., J. Chen, J. Neu, G. Oster, D. Zusman. (2010) Myxobacteria gliding motility requires cytoskeleton rotation powered by proton motive force. PNAS 108 (6) 2498-2503. This was a collaborative experimental/theoretical study that discovered an entirely new mechanism for bacterial propulsion. It is likely that many bacteria use the same machinery to swim and glide on surfaces. If so, it presents a large target for antibiotic designs. Gong, Z., N. Matzke, B. Ermentrout, D, Song, J. Vendetti, M. Slatkin, G. Oster. (2011) The evolution of neurally generated patterns on Conus shells. PNAS (In Press). This is another collaboration, this time between evolutionary biologists and theorists investigating the evolution of the patterns on sea shells. The work was based on an earlier model that demonstrated that sea shell patterns are generated by the secretion of pigment under control of the animal's nervous system. This study, therefore, is the first to document the evolution of a nervous system.
