We have thousands of apps on our computers and cell phones to serve our daily life and work. They are built by the programming languages in the information world. There are also thousands of molecular apps in our body to maintain numerous cellular activities to keep us healthy. A fundamental question we are motivated to answer is can we design those biomolecule apps as we develop apps in our cell-phone and computer? If we achieved this, we then can design molecule robots to cure diseases, molecular tools for advanced bio-analysis, novel biomaterials, and eventually even program life. The fundamental challenges toward this goal are to understand and manipulate complex biomolecular systems in biology. Biological systems are composed of billions of molecules (e.g., DNA, RNA, proteins) that encode different layers of information. The molecular systems in the complex biological environment are the cornerstone to understanding life and developing cutting-edge technologies to advance human healthcare. We are a group of scientists working on biomolecular design to address challenges in bio-nanotechnology, bio-analysis, and synthetic biology. We are actively working on following directions
(1) Developing new design rules to control the nucleic acid folding and dynamics, and understand the nucleic acid sequence to structure and function with experimental (high throughput sequencing and biochemistry assay) and computational approaches (e.g., neural networks and molecular dynamics) from sequence to structure and function, and vice versa (NAR 2020, JACS 2018, Angewandte Chemie 2017); I'm aiming to rationalize the natural bimolecular folding and function principle into algorithms in silico. The developed algorithm will enable us to understand the genetic code of DNA and reprogram the genome function
(2) Programming cell fates with computationally de-novo designed RNA machines to sense cellular cues and regulate gene expression via mRNA's dynamic folding (Cell 2020) and collective assemblies in vivo. Those dynamic folding and self-assembly of RNA in cellular environment will be used to study the disease mechanisms (e.g., intrinsic disordered aggregates) and develop novel therapeutics (e.g., controlled mRNA drug expression);
(3) Decoding cell/tissue function and disease mechanism at system level with massive molecular information (e.g., spatial genomics, transcriptomics, and proteomics) in situ resolved by DNA advanced molecular imaging tools. The developed imaging platform will be used to decode tissue architectures/functions (e.g., brain, retina) at molecular resolution and advanced diagnostics with digital pathology for clinical samples (e.g., Canner FFPE samples)(Nature Methods, 2023) .