Audrone Lapinaite is an assistant professor at the School of Molecular Sciences and the Biodesign Institute's Neurodegenerative Disease Research Center at ASU. She has long been interested in understanding the biology of DNA and RNA modifications in prokaryotic and eukaryotic cells. Audrone has received her undergraduate and master’s degrees in biochemistry from Vilnius University (Lithuania), where she was working with Prof. Saulius Klimasauskas and Dr. Grazvydas Lukinavicius on the engineering of bacterial DNA methylransferase to site-specifically tag genomic DNA.
Then she moved to the European Molecular Biology Laboratory (EMBL), Heidelberg (Germany) for her graduate studies in biochemistry and structural biology. At EMBL, she was working with Prof. Teresa Carlomagno on the structural and biochemical characterization of the box C/D RNA-protein complex (ribosomal RNA methyltransferase) using a combination of high-resolution (solution state NMR) and low-resolution (small angle neutron/X-ray scattering) approaches to compensate for the shortcomings of each individual technique. The two main findings of her graduate research are the discovery of a controlled sequential ribosomal RNA 2’-O-methylation mechanism, and the development of an integrative structure determination methodology to assess the structures and dynamics of large (up to 700 – 800 kDa) and flexible molecular assemblies in their native state in solution.
In 2015 she moved to the University of California, Berkeley as a Human Frontier Science Program (HFSP) postdoctoral fellow, working with Prof. Jennifer Doudna and Prof. Jamie Cate on the characterization of a CRISPR-locus associated programmable RNA and DNA binding Argonaute and on its application to specifically manipulate RNAs in cells by tethering diverse tags, such as fluorophores or effector proteins. This RNA targeting platform opens new horizons in probing endogenous RNAs’ and RNA modifications’ biology in live cells. In addition, she was also working on understanding the molecular mechanism of programmable DNA base editors (a fusion of CRISPR-Cas9 and either adenine or cytosine deaminases) to guide the design of smaller and more specific next generation DNA base editors.
Now at ASU her group focuses on elucidating the molecular mechanisms underlying the functional role of RNA base modifications in neurons in normal and pathological states using state-of-art structural and molecular biology approaches, including CRISPR-Cas mediated DNA and RNA targeting technologies. Her lab is also interested in characterizing and harnessing bacterial defense systems (e.g. CRISPR, restriction-modification etc.) for biotechnological and therapeutic applications.
Our group is interested in elucidating the molecular mechanisms underlying the functional role of RNA base modifications in neurons in normal and pathological states. We are also interested in characterizing and harnessing bacterial defense systems (e.g. CRISPR, restriction-modification etc.) for biotechnological and therapeutic applications. In our research we are using state-of-art structural and molecular biology approaches, including cryo-EM and CRISPR-Cas mediated DNA/RNA targeting technologies.
Lapinaite A.*, Knott G.J.*, Palumbo C.M., Lin-Shiao E., Richter M.F., Zhao K.T., Beal P.A., Liu D.R., Doudna J.A. DNA capture by a CRISPR-Cas9 guided adenine base editor. Science (2020) Jul 3; 369(6503):566-571.
Richter M.F.*, Zhao K.T.*, Eton E., Lapinaite A., Newby G.A., Thuronyi B.W., Wilson C., Koblan L.W., Zeng J., Bauer D.E., Doudna J.A., Liu D.R. Phage-Assisted Evolution of an Adenine Base Editor with Enhanced Cas Domain Compatibility and Activity. Nature Biotechnology (2020) Jul; 38(7):883-891.
Lapinaite A., Carlomagno T., Gabel F. Small-Angle Neutron Scattering of RNA-Protein Complexes. Methods in Molecular Biology (2020) Feb 1; 2113:165-188.
Lapinaite A., Doudna J.A., Cate J.H.D. Programmable RNA recognition using a CRISPR-associated Argonaute. PNAS (2018) Mar 27;115(13):3368-3373.
Graziadei A., Masiewicz P., Lapinaite A., Carlomagno T. Archaea box C/D enzymes methylate two distinct substrate rRNA sequences with different efficiency. RNA (2016) May;22(5):764-72.
Lapinaite A., Simon B., Skjaerven L., Rakwalska-Bange M., Gabel F., Carlomagno T. The structure of the box C/D enzyme reveals regulation of RNA methylation. Nature (2013) Oct 24;502(7472):519-23.
Kriukiene E., Labrie V., Khare T., Urbanaviciute G., Lapinaite A., Koncevicius K., Li D., Wang T., Pai S., Ptak C., Gordevicius J., Wang S.C., Petronis A., Klimasauskas S. DNA unmethylome profiling by covalent capture of CpG sites. Nature Communications (2013) 4:2190.
Ballaré C.*, Lange M.*, Lapinaite A.*, Martin G.M., Morey L., Pascual G., Liefke R., Simon B., Shi Y., Gozani O., Carlomagno T., Benitah S.A., Di Croce L. Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity. Nature Structural & Molecular Biology (2012) Dec;19(12):1257-65.
Lukinavicius G., Lapinaite A., Urbanaviciute G., Gerasimaite R., Klimasauskas S. Engineering the DNA cytosine-5 methyltransferase reaction for sequence-specific labeling of DNA. Nucleic Acids Research (2012) Dec;40(22):11594-602.
*designated equal contribution