Search for the Structural Basis of Biomacromolecular Function and Activity

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

We have made progress in six areas of our research program: 1. We have developed a new method to study RNA conformational space in a physiologically relevant solution using atomic force microscopy and a neural network. This work has been published (Degenhardt et al., Nature, 2025). 2. Using the novel method developed in my lab, we revealed the RNA conformational heterogeneity under a physiologically relevant solution and quantified motion amplitude and trajectories. This finding has fundamental implications in biomedicine and biotechnology, in addition to the basic theory about RNA biology. This work has been published (Lee et al., Nature, 2025). 3. We demonstrated the feasibility of using an RNA device to regulate gene expression of PD-1, a key immuno checkpoint receptor. This work is significant for finding a novel approach different from all known other conventional approaches for immunotherapy for cancer. This work has been published (Stagno et al., NAR, 2025). 4. We have made a major advance in developing an algorithm for the structure determination of heterogeneous RNA using cryoEM under a physiologically relevant solution and made several seminal discoveries. Currently, we are preparing a manuscript to report the results. 5. We have developed an algorithm to capture complete intermediate states of biochemical interactions/reactions under a physiologically relevant solution using cryoEM. This is a major advance in structural biology and makes it possible to capture the full process of biochemical interactions/reactions in molecular movies. We are completing this project and expect to compile a manuscript within this FY. 6. We have obtained the first picture of the HOTAIR lncRNA. This RNA is 2 kb long and functions like a "switchboard," directing molecular traffic, and is implicated in almost all forms of human cancer. This work is very significant for biomedicine and biotechnology, in addition to structural biology. To put it in perspective, it is not known if this RNA is structured and if its structure can be determined using existing technologies. We are at the doorstep of elucidating the 3D structure of this important RNA.