Tianbing Xia, Ph.D.
Education and Professional Affiliations
B.S., Chemistry, Peking University
M.S., Physical/Structural Chemistry, Peking University
Ph.D., Biophysical Chemistry, University of Rochester
Post Doctorate Scholarship, California Institute of Technology
Member, American Chemical Society
Overview
Our research aim to understand the principles of molecular recognition, biomolecular structures, folding and dynamics, and more importantly, the correlations between structures, energetics, dynamics, and functions of important biomolecules. We are addressing these problems by interdisciplinary approaches, employing a battery of state-of-the-art methodologies from the fields of modern molecular biology, biochemistry, chemical physics, and synthetic chemistry. We are developing novel structural biology tools, particularly, ultrafast laser spectroscopy, combined with other traditional spectroscopy, to probe nucleic acid and protein structures, nucleic acid-protein interactions, and the central roles that these interactions play in regulating important biological processes.
Molecular recognition: Cultivating the Femto RNA Land!
Biological macromolecules are structurally dynamical by nature, and they sample an ensemble of conformations at different timescales on a landscape that is defined by their chemical identity and environment. One of our current research focuses is on developing femtosecond resolved laser spectroscopy as a novel structural biology tool to analyze the heterogeneous structural ensembles of interesting biomolecules, particularly the ruggedness of the conformational landscape of functional RNAs, DNAs, proteins, and their complexes. This approach provides unique and quantitative information on biological structures as an ensemble rather than a single static or averaged frame. We are trying to understand the principles of RNA and protein folding and the consequence of the complicate conformational landscape in molecular recognition, and the effects of ligand-induced changes in the landscape. Structural heterogeneity and conformational dynamics can have great influence on functionality. The knowledge will form the basis for understanding the fundamental principles of molecular recognition.
We are also using the ultrafast spectroscopy as one of the main tools to probe complex RNA-protein, DNA-protein, and protein-protein interactions, and elucidate their roles in high-order functional macromolecular assemblies. We have previously demonstrated that this unique approach is a powerful one for elucidating complex interaction networks. Correlating structure, energetics, dynamics, and functions is the key to obtain a coherent picture of biological functions. The fundamental mechanism of transcription antitermination by N protein of phage lambda has been a long-standing mystery in gene regulation. We will test our hypotheses of how precise conformational arrangements and interactions are communicated by the participating factors in the complicated transcription complex.
We are also interested in using combinatorial selection as an approach to analyze RNA-protein interactions systematically. Chemical diversity is one of the keys to expanding our repertoire of RNA-binding ligands. We will develop unnatural peptide ligands (e.g., D peptides) via approaches that combine the power of mRNA display-based selection and reflection selection against important RNA targets, including regulatory RNA structures from HIV. We hope to deduce the rules of RNA recognition by natural and unnatural ligands and use that knowledge to rationally design ligands with enhanced recognition specificity and affinity towards important RNA targets.
The long term goals of analyzing complex RNA structures and RNA-protein interactions is to enhance our understanding of molecular recognition and enable us to design better ligands to understand and ultimately control biological processes.
Selected Publications:
1. Tianbing Xia, Chaozhi Wan, Richard W. Roberts, & Ahmed H. Zewail, “RNA-Protein Recognition: Single-Residue Ultrafas Dynamical Control of Structural Specificity and Function”, Proc. Natl. Acad. Sci USA. 102, 13013-13018 (2005).
2. Chaozhi Wan, Tianbing Xia, Hans-Christian Becker, & Ahmed H. Zewail, “Ultrafast Unequilibrated Charge Transfer: A New Channel in the Quenching of Fluorescent Biological Probes”, Chem. Phys. Lett., 412, 158-163 (2005).
3. Tianbing Xia, Adam Frankel, Terry T. Takahashi, Jinsong Ren, & Richard W. Roberts, “Context and conformation dictate function in a transcription antitermination switch”, Nat. Struct. Biol., 10, 812-819 (2003).
4. Tianbing Xia, Hans-Christian Becker, Chaozhi Wan, Adam Frankel, Richard W. Roberts, & Ahmed H. Zewail, “The RNA-protein Complex: Direct probing of the interfacial recognition dynamics and its correlation with biological functions”, Proc. Natl. Acad. Sci USA. 100, 8119-8123 (2003).
5. Tianbing Xia, David H. Mathews, & Douglas H. Turner, “Thermodynamics of RNA Secondary Structure Formation”, in vol. 6 of “Comprehensive Natural Products Chemistry”, ed. D.G. Söll, S. Nishimura, & P.B. Moore, pp. 21-47 (1999); reprinted in paperback as “RNA” in 2001 (Elsevier Science).
- Updated: February 6, 2006
