个人简介

1992-1996 Benjamin Franklin Scholar 2010 Pew Scholar

研究领域

Chemical Biology

RNAs are remarkable as both information carriers and structured functional macromolecules. Beyond their well-known role in the information transfer between DNA and proteins, RNAs act as catalysts (ribozymes) in many cellular processes such as protein synthesis, splicing, and tRNA maturation. In addition, RNA can fold to form small-molecule recognition elements (riboswitches) that regulate gene expression. It is clear that RNA structure and regulation is critical to a wide variety of cellular events, but the complexity of regulatory mechanisms is only now beginning to be appreciated. This duality of function makes RNAs and their chemical analogs ideal for in vitro selection and evolution experiments. In vitro selection is a powerful tool for rapid cell-free identification of specific binders or efficient catalysts from very diverse synthetic or genomic libraries, with complexities of up to about 10E16. Aptamers, RNAs with high binding affinity and specificity, are readily isolated and can be evolved further to improve or alter their function. For example, they have been developed to bind a large variety of small molecule targets, to act as drugs that bind proteins and cells in a tissue-specific manner, and to deliver cargoes to those cells. Similarly, ribozymes have been evolved in vitro to accelerate a wide variety of chemical reactions. We explore the biology and chemistry of RNA by utilizing in vitro selection techniques and structure-based bioinformatics to search for new catalytic RNAs in a variety of genomes. Through these RNAs, we look for novel modes of cell regulation. Another way in which we combine the study of RNA biology and chemistry is to use synthetic libraries to select aptamers and ribozymes with designed characteristics. Of particular interest is the selection of fluorogenic molecules that we will use to study RNA in live cells with hitherto unprecedented spatial and temporal resolution. To facilitate the selection process we are developing novel fluorescence-based methods to display and isolate fluorogenic nucleic acids.

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Manuel, G, Lupták, A, Corn, RM. (2016) A microwell–printing fabrication strategy for the on-chip templated biosynthesis of protein microarrays for surface plasmon resonance imaging. J Phys Chem C 120:20984-20990 Webb CH, Nguyen D, Myszka M, Lupták A. (2016) Topological constraints of structural elements in regulation of catalytic activity in HDV-like self-cleaving ribozymes. Sci Rep. 6:28179. doi: 10.1038/srep28179. Rampášek L, Jimenez RM, Lupták A, Vinar T, Brejová B. (2016) RNA motif search with data-driven element ordering..BMC Bioinformatics 17:216. doi:10.1186/s12859-016-1074-x Kozlyuk N, Sengupta S, Lupták A, Martin RW. (2016) In situ NMR measurement of macromolecule-bound metal ion concentrations. J Biomol NMR 64(4):269-273. doi: 10.1007/s10858-016-0031-3 Pobanz K and Lupták A (2016) Improving the odds: Influence of starting pools on in vitro selection outcomes. Methods 106:14-20 Jimenez RM, Polanco JA, Lupták A. (2015) Chemistry and Biology of Self-Cleaving Ribozymes.Trends in Biochemical Sciences 40(11):648-61. Long A, Liti G, Luptak A, Tenaillon O. (2015) Elucidating the molecular architecture of adaptation via evolve and resequence experiments. Nature Reviews Genetics 16(10):567-82. Lupták, A. (2015) Catalytic properties of RNA. in Discoveries in modern science: Exploration, invention, technology. Trefil, J. (ed.) Macmillan reference. Ho, B., Polanco, J., Jimenez, R.M. & Lupták, A. (2014) Discovering human RNA aptamers by structure-based bioinformatics and genome-based in vitro selection. Methods Enzymol. 2014;549:29-46.