02/24/20 - 4:00 PM to 5:00 PM
Special Seminar: Jonathan Sczepanski
Synthetic Chromatin and Mirror Image Oligonucleotides
The first part of this seminar will focus on our efforts to uncover the molecular mechanisms underlying the regulation of DNA repair proteins within chromatin. To facilitate these studies, we developed a “plug-and-play” approach for incorporating site-specifically positioned DNA modifications into oligonucleosome arrays reconstituted in vitro (i.e. synthetic chromatin). This approach allows precise control over the environment of a particular DNA modification, enabling a detailed analysis of the activities of associated repair proteins in a variety of prescribed chromatin states, both chemical and structural. Details regarding these studies, as well as our recent efforts to expand the plug-and-play approach into other areas of chromatin biochemistry, will be presented.
During the second part of this seminar, I will describe “heterochiral” nucleic acid technologies, which merge native D-DNA with its bioorthogonal enantiomer L-DNA in order to achieve novel functionality. In particular, we recently reported a strand-displacement methodology for transferring sequence information between oligonucleotide enantiomers, enabling the construction of DNA-based molecular circuits having fully-interfaced D-DNA and L-DNA components. On the basis of this approach, we have now successfully interfaced D-nucleic acid biomarkers (e.g. microRNAs) with L-DNA-based circuits in vitro and within living cells, laying the foundation for future development of advanced diagnostic devices. Details regarding our recent progress in this area will be presented.
- Deckard, C.E., Banerjee, D.R., Sczepanski, J.T. Chromatin Structure and the Pioneering Transcription Factor FOXA1 Regulate TDG-Mediated Removal of 5-formylcytosine from DNA. J. Am. Chem. Soc. 141, 14110–14114 (2019).
- Banerjee, D.R., Deckard, C.E., Elinsky, M.B., Batteas, J.D., Sczepanski, J.T. A Plug-and-Play Approach for Preparing Chromatin Containing Site-Specific DNA Modifications: The Influence of Chromatin Structure on Base Excision Repair. J. Am. Chem. Soc. 140, 8260–8267 (2018).
- Kabza, A.M., Young, B.E., Sczepanski, J.T. Heterochiral DNA Strand-Displacement Circuits. J. Am. Chem. Soc. 139, 17715–17718 (2017).
- Zhong, W., Sczepanski, J.T. A Mirror Image Fluorogenic Aptamer Sensor for Live-Cell Imaging of MicroRNAs. ACS Sens. 4, 566–570 (2019).
Jonathan Sczepanski’s research group combines expertise in chemical biology, nucleic acid chemistry, molecular biology, and directed evolution, in order to develop novel tools for studying, monitoring, and modulating nucleic acid-related biological processes. Current research areas include:
- Use of chemical biology approaches to investigate the relationships between chromatin structure and DNA modifications.
- Engineering L-DNA nanodevices and circuitry capable of analyzing and manipulating molecular information in living systems.
- Development of nucleic acid-based affinity reagents and catalysts for practical biomedical applications.
- Investigating how oligonucleotides of opposite stereochemistry interact, both in terms of molecular recognition and catalysis.
Sczepanski earned his bachelor’s degree in chemistry from the University of Minnesota, his doctorate from Johns Hopkins, and was a post-doctoral researcher at Scripps Research, before starting his independent career at Texas A&M, where he currently is an assistant professor.