SCIENCE AT THE EDGE SEMINAR SERIES Quantitative Biology & Modeling Seminar Friday, 30 March 2012 at 11:30am Room 1400 Biomedical and Physical Sciences Bldg. Refreshments at 11:15 Speaker: Chuan He Department of Chemistry and Institute for Biophysical Dynamics University of Chicago Title: Nucleic Acids Modification/Demodification and Probes for Live Cell Imaging Abstract: Reversible chemical modifications on nucleic acids and proteins determine cell fates. The five bases that comprise nucleic acids - adenine, guanine, cytosine, thymine, and uracil - can be chemically and enzymatically modified. These chemical events can have significant biological consequences, particularly for gene expression. I will present chemical strategies we have developed to enrich and sequence novel nucleic acid modifications in mammalian genome.{ref 1} Several AlkB family proteins have been identified in the human genome that may mediate nucleic acids' oxidation. Some of these proteins play critical roles in obesity/diabetes and various cancers. I will present our recent results that reveal the exact nucleic acid substrates and cellular function of some of these intriguing enzymes.{ref 2} Based on these discoveries we propose a new mode of biological regulation that depends on reversible RNA modification, for which we termed "RNA Epigenetics".{ref 3} I will also present our efforts to develop genetically encoded or small molecule-based probes for live cell imaging of metal ions and hydrogen sulfide.{refs 4,5} References 1. Song, C.-X.; Szulwach, K. E.; Fu, Y.; Dai, Q.; Yi, C.; Li, X.; Chen, C.-H.; Zhang, W.; Jian, X.; Wang, J.; Zhang, L.; Looney, T. J.; Zhang, B.; Godley, L. A.; Hicks, L. M.; Lahn, B. T.; Jin, P.* and He, C.* _Nature_Biotechnol._ 29, 68-72 (2011). 2. Yi, C.; Jia, G; Hou, G.; Dai, Q.; Zhang, W.; Zheng, G.; Jian, X.; Yang, C.-G.; Cui, Q. and He, C. _Nature_ 468, 330-333 (2010). 3. He, C. _Nature_Chem._Biol._ 6, 863 (2010). 4. Wegner, S.; Arslan, H.; Sunbul, M.; Yin, J; He, C. _J._Am._Chem._Soc._ 132, 2567-2569 (2010). 5. Qian, Y.; Karpus, J.; Kabil, O.; Zhu, H.-L.; Banerjee, R.; Zhao, J.; He, C. _Nature_Commun._ 2, 495 (2011).