Tracy Nixon
Professor of Biochemistry and Molecular Biology
332 South Frear LaboratoryUniversity Park, PA 16802
Research Interests
1. Functional bases of signal transduction and gene regulation by AAA+ATPases in bacteria.
2. Degradation of lignocellulose by cellulases.
3. Synthesis of cellulose.
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
Research Summary
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.
Expertise
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).
2003 
2003
2006
2007 
2007
2010
Representative Publications
- Chakraborty, A., Wang, D., Ebright, Y.W., Korlann, Y., Kortkhonjia, E., Chowdhury, S., Wigneshweraraj, S., Irschik, H., Jansen, R., Nixon, B.T., Knight, J., Weiss, S., and Ebright, R.H. 2012 Opening and closing or the bacterial RNA polymerase clamp. Science, accepted.
- Li, P., Banjade, S., Cheng, H.-C., Kim, S., Chen, B., Guo, L. Llaguno, M., Hollingsworth, J.V., King, D.S., Banani, S.F., Russo, P.S., Jiang, Q.-X., Nixon, B.T., and Rosen, M.K. 2012. Phase transitions in the assembly of multivalent signalling proteins. Nature 483, 336-340.
- Baoyu Chen, Tatyana A. Sysoeva, Saikat Chowdhury, Liang Guo, Sacha De Carlo, Jeffrey A. Hanson, Haw Yang, and B. Tracy Nixon. 2010. Engagement of Arginine Finger to ATP Triggers Large Conformational Changes in NtrC1 AAA+ ATPase For Remodeling Bacterial RNA Polymerase. Structure. 2010 Nov 10;18(11):1420-30.
- Burrows, P.C., Joly, N., Cannon, W.V., Camara, B.P., Rappas, M., Zhang, X., Dawes, K., Nixon, B.T., Wigneshweraraj, S.R., and Buck, M. 2009. Coupling sigma factor conformation to RNA polymerase reorganisation for DNA melting. J. Mol. Biol. 387, 306-319.
- Burrows, P.C., Schumacher, J., Amartey, S., Ghos, T., Burgis, T.A., Zhang, X., Nixon, B.T. and Buck, M. (2009) Functional roles of the pre-sensor I insertion sequence in an AAA+ bacterial enhancer binding protein. Mol. Micro. doi:10.1111/j.1365-2958.2009.06744.x.
- Burrows, P. C., Joly, N., Nixon, B.T. and Buck, M. (2009) Comparative Analysis of Activator-E?54 Complexes formed with Nucleotide-Metal Fluoride Analogues. Nuc. Acids Res. 37: 5138-5150.
- Chen, B., Sysoeva, T.A., Chowdhury, S., Guo, L., and Nixon, B.T. 2009. ADPase activity of recombinantly expressed thermotolerant ATPases may be caused by co-purification of adenylate kinase of Escherichia coli. FEBS J 276: 807-815.
- Chen, B., Sysoeva, T.A., Chowdhury, S., and Nixon, B.T. 2008. Regulation and action of the bacterial enhancer binding AAA+ ATPases. Biochem. Soc. Transact. 36, 89-93.
- Doucleff, M., Pelton, J.G., Lee, P.S., Nixon, B.T. and Wemmer, D.E. 2007. Structural basis of DNA recognition by the alternative sigma-factor, sigma54. J. Mol. Biol. 369, 1070-1078. Summary figure used for cover of J. Mol. Biol. 369 (2007).
- Chen, B., Doucleff, M., Wemmer, D.E., De Carlo, S., Huang, H.H., Nogales, E., Hoover, T.R., Kondrashkina, E., Guo, L., and Nixon, B.T. 2007. ATP ground- and transition states of bacterial enhancer binding AAA+ ATPases support complex formation with their target protein, ?54. Structure 15, 429-440. Summary figure used for the cover of Structure 15 (2007).
- De Carlo, S., Chen, B., Hoover, T.R., Kondrashkina, E., Nogales, E. and Nixon, B.T. 2006. The structural basis for assembly and function of the transcriptional activator NtrC. Genes & Dev 20, 1485-1495. Summary figure used for cover of Genes & Dev 20 (2006).
