My lab has made progress on several fronts. 1. we elucidated the physical basis for lattice phase transition triggered by ligand and discovered a fundamental phenomenon called molecular synchronization in crystal lattices. Currently, we are preparing the manuscript to report the results. This project is a long-term and very fundamental to visulization of molecular movies 2. we have designed several RNA devices that have near ideal kinetic characteristics for potential clinic applications. Currently, we are further optimizing those devices in vitro and planning to further characterize them in mouse and human lymphocyte cells. Our eventual plan is to collaborate with the CCR clinicians in Bethesda for potential applications in immunotherapy. Thus this project is potentially translational. 3. We made progress in determining RNA three-dimensional structures in aqueous solution using atomic force microscopy. RNA molecules tend to be very dynamics and flexible, and is generally not amenbale to structure characterization by conventional methods such as NMR, crystallography or cryo-EM. We have overcome several technical challenges. Now we are able to visulaize double strand nucleic acids in aquous solution with resolution up to major/minor grooves. At the presnet time, we are testing the technique using RNA with a known structure to validate our method.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010379-20
Application #
10014360
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
20
Fiscal Year
2019
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Stagno, J R; Liu, Y; Bhandari, Y R et al. (2017) Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography. Nature 541:242-246
Stagno, Jason R; Bhandari, Yuba R; Conrad, Chelsie E et al. (2017) Real-time crystallographic studies of the adenine riboswitch using an X-ray free-electron laser. FEBS J 284:3374-3380
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Chen, Bin; Zuo, Xiaobing; Wang, Yun-Xing et al. (2012) Multiple conformations of SAM-II riboswitch detected with SAXS and NMR spectroscopy. Nucleic Acids Res 40:3117-30
Liao, Jack C C; Lam, Robert; Brazda, Vaclav et al. (2011) Interferon-inducible protein 16: insight into the interaction with tumor suppressor p53. Structure 19:418-29

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