In biological systems, there are billions of biomolecules orchestrating together to maintain cellular functions. Those biomolecules contains different levels of biological information, such as primary sequence, folded structures, biological function, and chemical connectivity, from single cell to tissue scale. To better understand biological mechanisms and improve human healthcare, it is critical to visualize and manipulate these biomolecular activities in cells. The development of structural and functional biomolecular tools is one of key pillars to achieve these goals. For instance, designed biomolecular probes for bio-imaging can help massively visualize biomolecules in cells and tissues, which is necessary to reveal the complex cellular organizations and behaviors. Beyond visualization, designed functional biomolecular tools can also regulate cellular activities by interfacing them with biological roles to either record cellular events or control cell fates.
Motivated by the scientific challenges to decode and regulate complex biological systems, the research at Hong Lab will move along on the following tracks:
(1) Decoding molecular systems in biology: Biological systems are self-organized biomolecules with different species, quantities and spatial locations within cells and tissues. We aim to develop molecular technologies based on programmable DNA reactions on top of fluorescence microscopy （e.g. DNA Thermal-plex imaging) and next generation sequencing to analyze biomolecules (e.g., DNAs, RNAs, and proteins) in cells and tissues with high sensitivity, high multiplexity, and high throughput to understand how they relate to human health.
(2) Bio-programming: Cell performs computation with the principle we have yet to understand. We aim to develop principles and algorithms to first understand the biomolecules from sequence to structure and function (e.g., crowder-oxDNA), and then use that algorithm to design functional and structural biomolecules (e.g., SNIPR). Those computer-designed molecules will be used to interface the biology to program cellular behaviors within the cell and cross the cells.
(3) Conctrol/understand biomolecular dynamic circuits: Biomolecules are not static in cells, they interact with each other to have signal exchange and maintain cellular functions. We aim to understand and control the dynamic structure change of biomolecules to program cellular gene expression and develop new gene diagnostics and therapeutics (e.g., SNIPR).
(4) Conctrol/understand the biomolecular assembly: Molecular self-assembly is everywhere. Biomolecules also self-organize in cells and the collective self-organization relates to its functions and diseases. We aim to understand and control the collective assembly behavior of nucleic acid both in vivo and in vitro (e.g., layered framework DNA architectures for DNA origami and DNA crystals) from nanoscale to macroscale and how it can be use to biomedical applications .
Motivated by the scientific challenges to decode and regulate complex biological systems, the research at Hong Lab will move along on the following tracks:
(1) Decoding molecular systems in biology: Biological systems are self-organized biomolecules with different species, quantities and spatial locations within cells and tissues. We aim to develop molecular technologies based on programmable DNA reactions on top of fluorescence microscopy （e.g. DNA Thermal-plex imaging) and next generation sequencing to analyze biomolecules (e.g., DNAs, RNAs, and proteins) in cells and tissues with high sensitivity, high multiplexity, and high throughput to understand how they relate to human health.
(2) Bio-programming: Cell performs computation with the principle we have yet to understand. We aim to develop principles and algorithms to first understand the biomolecules from sequence to structure and function (e.g., crowder-oxDNA), and then use that algorithm to design functional and structural biomolecules (e.g., SNIPR). Those computer-designed molecules will be used to interface the biology to program cellular behaviors within the cell and cross the cells.
(3) Conctrol/understand biomolecular dynamic circuits: Biomolecules are not static in cells, they interact with each other to have signal exchange and maintain cellular functions. We aim to understand and control the dynamic structure change of biomolecules to program cellular gene expression and develop new gene diagnostics and therapeutics (e.g., SNIPR).
(4) Conctrol/understand the biomolecular assembly: Molecular self-assembly is everywhere. Biomolecules also self-organize in cells and the collective self-organization relates to its functions and diseases. We aim to understand and control the collective assembly behavior of nucleic acid both in vivo and in vitro (e.g., layered framework DNA architectures for DNA origami and DNA crystals) from nanoscale to macroscale and how it can be use to biomedical applications .
References:
- Fan Hong, Jocelyn Y. Kishi1, Ryan N. Delgado, Jiyoun Jeong, Sinem K. Saka, Hanquan Su, Constance L. Cepko, Peng Yin*. Thermal-plex: Fluidic-free, rapid sequential multiplexed imaging with DNA encoded thermal channels. Nature Methods, 2023, In press.
- Fan Hong, Duo Ma, Kaiyue Wu, Lida A. Mina, Rebecca C. Luiten, Yan Liu, Hao Yan*, Alexander A. Green*. Precise and Programmable Detection of Mutations Using Ultraspecific Riboregulators, Cell, 2020, 180, 1018-1032.
- Fan Hong, John Shreck, Petr Sulc, Understanding DNA interactions in crowded environments with a coarse-grained model, Nucleic Acid Research, 2020,48,10726.
- Fan Hong, Shuoxing Jiang, Xiang Lan, Raghu Pradeep Narayanan, Petr, Sulc, Fei Zhang, Yan Liu, Hao Yan, Layered-Crossover Tiles with Precisely Tunable Angles for 2D and 3D DNA Crystal Engineering, J. Am. Chem. Soc. 2018, 140, 14670-14676.
- Fan Hong, Shuoxing Jiang, Tong Wang, Yan Liu, Hao Yan, 3D Framework DNA origami structure with layered crossover motifs. Angew Chem Int Ed, 2016,55, 12832-12835.