Jingdong Ye

Biochemistry and Bioorganic chemistry, Organic synthesis, Structural Biology in RNA related biological mechanism and drug discovery

Assistant Professor of Chemistry Ph.D., University of Chicago Phone: (407) 823-2136 Office: CH 327 E-mail: jye@mail.ucf.edu CV: Download

Position available

One technician position is currently available.
Requirements: B. S., one year's experience in biochemistry lab
Experiences in RNA preparation and basic RNA biochemistry techniques are desirable.
Term: one year. Renewal will be dependent on performance and funding.
Salary: negotiable.

Research

Riboswitches are an exciting new frontier in the RNA field and drug discovery field (Winkler & Breaker Annu. Rev. Microbiol. 2005, 59, 487-517). They are cis-acting mRNA elements that regulate gene expression by direct binding to small molecule metabolites. Upon binding of the biologically important metabolites, riboswitches undergo conformational changes, which may affect the structure of the associated expression platforms. As they are generally well populated and often controlling essential life and virulence genes in many human pathogenic bacteria and fungi, they stands for the promising candidates for novel antibiotic drug targets. Its importance has been underscored by the rapidly emerging issue of antibiotic resistance in modern medicine. Most current prescribed antibiotics are based on decades-old chemical scaffolds and target a narrow range of cellular processes. New chemical scaffolds and new targets need to be discovered to replenish our antibiotic arsenal. Riboswitches represent one such class of antibiotic drug targets as they interact with variety of structurally distinct small organic molecules and they control a vast range of gene function. Our lab aims at two aspects of this exciting project:

• Functional and structural underpinning of several representative riboswitches.

The central feature for the riboswitch to achieve its function is the interaction between riboswitches and small organic metabolite molecules. Elucidation of the structure of the metabolite sensing domain (aptamer) will improve our understanding of how riboswitches control the perturbation of the expression domain and regulate gene expression through transcriptional termination, translational initiation, or alternative splicing. We'll combine nucleic acid chemical synthesis, biochemistry and site directed mutagenesis to probe the solution structure and the interaction between riboswitches and their cognate metabolites. In addition, as a highly rewarding and informationally rich endeavor, X-ray crystallography is also used to obtain high-resolution structure information of the intricate binding network between riboswitches and their metabolites. A technique that greatly increase the success of the crystallography effort, termed Chaperone Assisted RNA Crystallization (CARC), has been developed by the PI during his postdoctoral study. This involves first selection and screening for specific RNA binding antibody fragments (Fab) and then co-crystallizion of the Fab-RNA complex. As Fab provides important crystal contact and initial phasing information, this technique is viewed as a breakthrough in RNA crystallography.

• Elucidating the metabolite analog binding energetics and designing, synthesizing and screening for novel antibacterial compounds.

Using the information obtained from biochemical and structural techniques, we can design metabolite analogs binding to riboswitches. We will begin with those riboswitches whose crystal structure have already been solved. By varying the metabolite functional groups dispensable for riboswitch binding systematically, we can obtain metabolite analog binding energetics which will help us design better and novel inhibitors (antibiotic drugs for human pathogenic bacteria) for the riboswitch function. This project involves extensive organic synthesis. The students will have a choice to either collaborate with biochemists within the group or learn necessary biochemical techniques in the binding measurement and future drug efficacy test.

Students

Highly motivated students who are open-minded and good at learning any above mentioned techniques are welcome in our lab. Students will be exposed to almost all aspect of synthetic organic, bioorganic, biochemical, and structural biological techniques and can shape themselves by selectively mastering some of these techniques according to their future industrial or academic goals.

Selected Publications

1. Jing-Dong Ye, Valentina Tereshko, John K. Frederiksen, Akiko Koide, Frederic A. Fellouse, Sachdev S. Sidhu, Shohei Koide, Anthony A. Kossiakoff, Joseph A. Piccirilli (2008) "Synthetic antibodies for specific recognition and crystallization of structured RNA" PNAS, 105, 82-87.
   
   
   
   • Featured in the Dec 24, 2007 issue of C & EN.
   • Highlighted in Nat. Methods 2008, 5, 220.
   • Highlighted in ACS Chem. Biol. 2008, 3, 81.
   • Highlighted in the Feb 14, 2008 issue of SciBX (Science-Business eXchange)
   • Selected for Faculty of 1000 Biology, http://www.f1000biology.com/article/id/1097573/evaluation


2. Jing-Dong Ye, Christofer D. Barth, Potluri S. R. Anjaneyulu, Thomas Tuschl, Joseph A. Piccirilli (2007) "Reactions of Phosphate and Phosphorothiolate Diesters with Nucleophiles: Comparison of Transition State Structures" Org. Biomol. Chem., 5, 2491-2497.


3. Jing-Dong Ye, Nan-sheng Li, Qing Dai, Joseph A. Piccirilli (2007). "The mechanism of RNA stand scission: experimental measure of βnuc." Angew. Chem. Int. Ed., 46, 3714-3717.
   
   
   • Selected as VIP (very important paper) by Angew. Chem. Int. Ed.


4. Jing-Dong Ye, Xiangmin Liao, and Joseph A. Piccirilli (2005). "Synthesis of 2’-C-difluoromethyl ribonucleosides and their enzymatic incorporation into oligonucleotides." J. Org. Chem., 70, 7902-7910.


5. Peter M. Gordon, Robert Fong, Nan-Sheng Li, Shirshendu Deb, Jason P. Schwans, Jing-Dong Ye, Joseph A. Piccirilli (2004) . "New Strategies for exploring RNA’s 2’-OH expose the importance of solvent during group II intron catalysis." Chemistry & Biology, 11, 237-46.


6. Zheng-Yun J. Zhan, Jingdong Ye, Xiaoyu Li, David G. Lynn (2001). "Replicating DNA Differently." Current Organic Chemistry, 5, 885.


7. Jingdong Ye, Yahaloma Gat, David G. Lynn (2000). "Catalyst for DNA Ligation: Towards a Two-Stage Replication Cycle." Angew. Chem. Int. Ed., 39, 3641-3643.