Cellular recording and lineage tracing enabled by CRISPR technology
Biotechnologies have advanced to a stage where we can understand in exquisite detail the internal state of a cell. Far fewer tools have been developed that can record a cell’s history and explain how this history dictates its present and future states. For example, lineage tracing can uncover a cell’s origin and provide crucial insights into tissue development and homeostasis, yet traditional lineage tracing approaches offer only a low resolution history of the cell and cannot be applied to optically opaque tissues or physically inaccessible contexts that prevent the use of imaging techniques. The Tang group aims to combine the CRISPR technology with protein engineering to develop a targeted in situ DNA diversification tool, enabling the construction of complex synthetic memories in live cells for single-cell lineage tracing.
Drug development by constructing and screening highly functionalized cyclic peptide libraries
Peptides are extremely potent protein-protein interaction modulators and protein function regulators owing to their ability to recognize solvent-exposed, flat protein surfaces. Cyclic peptides are particularly promising as they can bind to target biomolecules with improved affinity and specificity and are less susceptible to protease degradation. Motivated by their therapeutic potential, the Tang group constructs highly functionalized cyclic peptide libraries using a novel route, taking advantage of the biosynthetic machinery of ribosomal natural products. Using a droplet-based selection system, these libraries will be screened for activities of interest in disease-relevant cell models, thereby realizing the ultimate therapeutic potential of peptide natural products.
Sulfur modifications in DNA and RNA and their mechanisms of formation
Chemically modified bases are ubiquitously found in organisms and play essential roles in biology. As the sixth most abundant element in living organisms, sulfur has been identified in both RNA and DNA. However, the distribution patterns and the mechanisms of formation for these modifications are not fully understood. The Tang lab develops modification-sensitive sequencing techniques to map known and novel sulfur modifications in DNA and RNA at the base resolution. The Tang group also studies the mechanisms of formation as well as the regulatory roles of sulfur modification in nucleotides, aiming to broaden the current understanding of epigenetics and epitranscriptomics. Finally, as a biotechnological tool, bases contain sulfur modifications will be applied as labeling probes to study genome and transcriptome dynamics.
