We are interested in applying synthetic biology methods and novel genetic engineering tools to rationally design and engineer cells that can sense and actuate complex functions. We have engineered new genetic devices that couple human GPCR recceptor molecules to the CRISPR-dCas9 effectors, such that cells equipped with this device can detect extracellular signals (by GPCR) and control endogenous gene expression (by dCas9). The engineered devices and circuits allow potentially better controlling of immune cells to integrate signals and conditionally medulate its tumor killing function. Examples include:

CRISPR for gene circuit construction and synthetic biology (Cell 2015; Nature Methods 2016)

GPCR-CRISPR device for sensor-actuator cell design (Nature Communications 2017)

The genome has intricate controls of its function, usually in a highly quantitative, coordinated and dynamic manner. Studies of genetics usually focused on how bases (A/T/C/G) lead to a function, or binary presence of absence of genes or regulatory elements for controlling its function, rather than seeking for a comprehensive dynamic and quantitative picture. For example, it remains major questions how quantitative gene expression leads to different functions, or how multiple regulatory elements (e.g., enhancers) work together to control diverse outcomes of the genome (considering it is the same DNA sequence). Driven by curiosity and availability of new tools, we aim to apply genetic engineering and other high-throughput perturbation and measure methods to study how genes and regulatory elements quantitatively contributes to the overall function fo the genome. We are also very interested in exploring how epigenetics (chemical modifcations of the DNA or nucleosomes) modulate and affect the spatial and temporal "parameters" of the "genomic algorithm".