• Faculty Directory

Andrew Hausrath

Education and Appointments

• BA (Mathematics) 1991, University of California, Santa Cruz
  
• BA (Physics) 1991, University of California, Santa Cruz
  
• PhD (Chemistry) 2000, University of Oregon
  

Research Interests

• Biochemistry
  
• Physical
  
• "Theory, Modeling, and Simulation"
  
• Biophysics
  
• Protein and Membrane Biochemistry
  
• Structural Biology
  

Research Summary

Geometry and mechanics of higher-order biological structure

My research goal is to understand the organizing principles governing the action and form of macromolecular complexes. Most biological processes employ proteins as the active elements. However, the majority of processes are accomplished by large assemblies comprised of many different proteins, rather than by single proteins acting in isolation. While a great deal of detail is known about the structure of many individual proteins which comprise the constituent parts of these complexes, in only a few cases is there a comparable level of understanding of the action of the complex as a whole. In essence, the field currently has a detailed catalog of the parts from which such biological machines are constructed, but largely lacks an understanding of how these parts are put together, and how the properties of individual parts contribute to the function of the machine as a whole.

My lab employs a combination of theoretical and experimental approaches to address this gap in our understanding. On the theoretical side, a central theme has been the application of differential geometry to address such questions in structural biology. This mathematical discipline can be thought of as a precise language for the description of abstract shapes and forms, and it has proved to be a very versatile formalism for the analysis of the complex three-dimensional forms of proteins and their complexes. Using this formalism we develop theoretical models which can then be tested in the laboratory, and which prompt experiments needed to further develop the models. On the experimental side, we study the structures of proteins and complexes using X-ray crystallography, microscopy, and biophysical techniques. Proteins of certain classes are heavily represented as components of complexes. These include repeat proteins, coiled-coils, and other symmetric folds. The modular nature of these proteins may facilitate their use within complexes, and also simplifies their mathematical representation. Hence these are of particular interest to us. Knowledge of the structures and properties of the proteins which function within higher-order complexes then stimulates development of improved models and theory about how such complexes carry out their functions in the cell.

Systems of current interest include the ATP synthase, the signaling hormone adiponectin, and the higher-order organization of chromatin in the nucleus.

Selected Publications

Publications

• Briggs, D., Jones, C., Mashalidis, E., Nunez, M., Hausrath, A.C., Wysocki, V., and Tsao, T., Biochemistry, 2009, Disulfide-Dependent Self-Assembly of Adiponectin Octadecamers from Trimers and Presence of Stable Octadecameric Adiponectin Lacking Disulfide Bonds, 48(51), 12345-12357.

• Hausrath A.C. and Goriely, A., Journal of Applied Crystallography, 2009, The Fourier Transforms of Curves and Filaments and their Applications to Low Resolution Crystallographic Data, 42, 268-278.

• Goriely, A., Neukirch, S., and Hausrath, A. C., International Journal of Bioinformatics Research and Applications, 2009, Polyhelices Through N Points, 5(2), 118-132.

• Lowry, D.F., Hausrath, A.C., and Daughdrill, G.W., Proteins: Structure, Function and Bioinformatics, 2008, A Robust Approach for Analyzing a Heterogeneous Structural Ensemble, 73(4), 918-928.

• Neukirch, S., Goriely, A., and Hausrath, A. C., International Journal of Non-Linear Mechanics, 2008, Elastic Coiled-Coils Act as Energy Buffers in the ATP Synthase, 43(10), 1064-1073.

• Neukirch, S., Goriely, A., and Hausrath, A. C., Physical Review Letters, 2008, Chirality of Coiled-Coils: Elasticity Matters, 100, 038105.

• Hausrath, A. C. and Goriely, A., Journal of Structural Biology, 2007, Continuous Representations of Proteins: Construction of Coordinate Models from Curvature Profiles, 158(3), 267-281.

• Hausrath, A. C., Journal of Chemical Physics, 2006, A Kinetic Theory of Tertiary Contact Formation Coupled to the Helix-Coil Transition in Polypeptides, 125(8), 084909.

• Patki AU, Hausrath AC, Cordes MH., Journal of Molecular Biology, 2006, High Polar Content of Long Buried Blocks of Sequence in Protein Domains Suggests Selection Against Amyloidogenic Non-polar Sequences, 362(4), 800-809.

• Hausrath, A. C., Protein Science, 2006, A Model for the Coupling of á-Helix and Tertiary Contact Formation, 15(9), 2051-2061.

• Xian, W. and Connolly, P.J. and Oslin, M. and Hausrath, A.C. and Osterhout. J.J., Protein Science, 2006, Fundamental Interactions in Protein Folding: Measuring the Energetic Balance Between Helix Formation and Hydrophobic Iteractions, 15(9), 2062-2070.

• Kittleson JT, Loftin IR, Hausrath AC, Engelhardt KP, Rensing C, McEvoy MM., Biochemistry, 2006, Periplasmic Metal-Resistance Protein CusF Exhibits High Affinity and Specificity for Both Cu(I) and Ag(I), 15(4), 753-760.

• Hausrath, A. C. and Goriely, A., Protein Science, 2006, Repeat Protein Architectures Predicted by a Continuum Representation of Fold Space, (4), 753-760.