In biological systems, there are billions of biomolecules orchestrating together to maintain cellular functions. Those biomolecules contain 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 and tissues to study and control their behaviors. The development of structural and functional biomolecular tools is one of the 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 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 next-generation molecular technologies with novel molecular probes for fluorescence microscopy （e.g. DNA Thermal-plex imaging) and next generation sequencing to analyze cellular targets in cells and tissues with high sensitivity, high multiplexity, and high throughput to access the bio-molecular information untapped before. We'll then use those collected biomolecular information to understand how cell regulate its function and how they relate to human health.
(2) Bio-programming: A cell is a complex genetically coded life system with its DNA sequence, it performs computation with the principle we have yet to understand. We aim to develop principles and computational algorithms (e.g., crowder-oxDNA) to first understand the biomolecular folding from sequence to structure and how it related to its biological function, particularly about RNA folding and its biological function at current stage . The developed algorithm can then be used to design functional and structural biomolecules, such as ribogulators (e.g., SNIPR), aptamers. Those computer-designed molecules will be used to interface the biology to program cellular behaviors within the cell and cross the cells, eventually build living cellular devices to monitor environmental signal or cure diseases.
(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 circuit. Those biomolecular circuit can be used to process complex cellular signals and reprogram cellular behaviors for new therapeutics and diagnostics (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 to build new form of matter. We'll then study how those new matter form can be used to advance the understanding of human healthcare and be used for 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 next-generation molecular technologies with novel molecular probes for fluorescence microscopy （e.g. DNA Thermal-plex imaging) and next generation sequencing to analyze cellular targets in cells and tissues with high sensitivity, high multiplexity, and high throughput to access the bio-molecular information untapped before. We'll then use those collected biomolecular information to understand how cell regulate its function and how they relate to human health.
(2) Bio-programming: A cell is a complex genetically coded life system with its DNA sequence, it performs computation with the principle we have yet to understand. We aim to develop principles and computational algorithms (e.g., crowder-oxDNA) to first understand the biomolecular folding from sequence to structure and how it related to its biological function, particularly about RNA folding and its biological function at current stage . The developed algorithm can then be used to design functional and structural biomolecules, such as ribogulators (e.g., SNIPR), aptamers. Those computer-designed molecules will be used to interface the biology to program cellular behaviors within the cell and cross the cells, eventually build living cellular devices to monitor environmental signal or cure diseases.
(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 circuit. Those biomolecular circuit can be used to process complex cellular signals and reprogram cellular behaviors for new therapeutics and diagnostics (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 to build new form of matter. We'll then study how those new matter form can be used to advance the understanding of human healthcare and be used for 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.