BMMB, MCIBS, PLBIO
Graduate Course: Computers in Molecular Biology
Molecular biologists and biochemists need to process data and create figures to help others quickly grasp the results. Increased processing capacity in computers has dramatically affected how one accomplishes these tasks. This course is designed to help graduate students in the BMMB and related programs to understand and apply modern quantitative analysis of data.
Please visit the course website to learn more:
Computers for Biochemists and Molecular Biologists
As postdoc I discovered the bacterial two-component signal transduction paradigm. This method of information processing is the predominant form used by bacteria, and it is also present in fungi and plants. Learning how these signals are processed will help us defend against bacterial pathogens and manipulate beneficial processes such as biological nitrogen fixation, chemotaxis, cell cycle regulation, fruiting body formation, sporulation, osmoregulation and fruit ripening. Using genetics, molecular biology, biochemistry and structural biology (crystallography, small-angle X-ray scattering, electron microscopy) my lab has discovered unexpected diversity in the mechanism of how a phosphorylated second component can regulate assembly of a AAA+ ATPase motor. We are now developing a model for how ATP binding and hydrolysis are harnessed by a AAA+ ATPase motor to perform mechanical work on bacterial RNA polymerase. Our collaborative studies (David Wemmer and Eva Nogales, UC Berkeley; S. De Carlo, CUNY, Haw Yang, Princeton) have resulted in the journal covers shown below, and helped establish the BioCAT (Director – Tom Irving; Advanced Photon Source and Illinois Institute of Technology) as a world premier site for small-angle X-ray scattering.
In addition to that major theme of research, I participate in two collaborations in the field of energy biosciences. The plant cell wall is composed of a primary cell wall and when the cell ages, a secondary wall is formed of which a large percentage is made of cellulose. If made accessible, such cellulose is a potentially rich source of reduced carbon for microbial fermentations yielding ethanol as a future combustible energy source. In 2007 the United States embarked on a federal mandate to produce about 20 billion gallons of cellulosic ethanol by the year 2017. Despite such intense interest, our ability to access this carbon is economically hampered because the cellulose is sequestered from water in crystalline fibers and amongst lignin and other polysaccharide polymers. These barriers make it difficult to depolymerize cellulose into glucose. Efforts to bring the process to economic feasibility thus focus on enhancing access by altering the pretreatment processes and properties of depolymerizing cellulases.
The first of these two bioenergy projects arises from the fact that only enzymes produced by fungi are capable of breaking down the lignin barrier to gain full access to the energy-rich cellulose component of lignocellulose. Harnessing that efficiency has thus far eluded us, hindering our efforts to economically produce liquid fuels from plant biomass. This obstacle arises from our lack of understanding the cellular and molecular mechanisms that underlie the fungus-enzyme-lignocellulose gestalt. Working with Haw Yang (Princeton University), Chemistry Department; and Ming Tien, Biochemistry and Molecular Biology, Penn State), we have launched a new DOE-funded research program to address this challenging problem.
The second of the bioenergy projects emerges from the observation that despite the overwhelming ecology and economical significance of cellulose synthesis, relatively little is known about the biochemistry of this process. Much knowledge would be gained if a 3-dimensional structure were available to guide research of cellulose synthesis. Combined with the recently-described gradient fixation method of Stark, prior work shows that 3D image reconstructions are possible for cellulose synthase from epicotyls of the Azuki bean Vigna angularis, and possibly for the model plant Arabidopsis thaliana. I collaborate with the Tien and Haigler Labs to apply my expertise in this methodology to accomplish this research objective, with seed grant funding from the DOE's Center for Lignocellulose Structure and Formation.
Molecular genetics, general biochemistry, structural biology (gene cloning, expression, protein purification, enzyme assay, analytical ultracentrifugation, solution X-ray and neutron scattering, crystallography, and 3D reconstruction from single particles in electron micrographs).