Research Overview

We are interested in developing novel methods for the rational design and engineering of the human genome and cellular functions. We regard such an approach as “discovery-based synthetic biology”, which aims to harness and repurpose naturally occurring molecules and genetic elements as new tools for genome and cell engineering. In the past, we have engineered the nuclease-dead Cas9 (dCas9) from the natural CRISPR system. We used the dCas9 molecule as a platform to enable multiple engineering functions: transcription regulation of the genome (CRISPRi), genome imaging in living cells, and genome-wide functional screening of genes and regulatory elements. Similar concepts can be applied to the vast molecules that exist in Nature which are unknown to our knowledge. Because of this dual purpose of both “understanding and engineering”, we call it discovery-based synthetic biology. Currently, our lab is interested in the following three bioengineering topics:

  • ·       New molecules and approaches for genome engineering.
  • ·       Cell-based rational and complex immunological engineering.
  • ·       Stem-cell-based programmable regenerative medical engineering.

Rationale

The advent of CRISPR tools made it orders of magnitude easier for engineering the genome in diverse organisms. However, there are still a few clouds shading the whole field. For example, the efficiency of precise genome editing in primary cells remained very low; paralleled activation and repression of hundreds of genes still seems a daunting task to try; the roles of the dark matter of the genome, the 98% of the nucleotides in the nucleus, remain a piece of puzzle. To this end, we draw a conclusion that it is not a single magic molecule that solves the problem, but rather a suite of toolkits with a deep understanding of the work of the genome will be the ultimate solution.

Therefore, in the Qi Lab we aim to develop such a suite of tools for genome engineering. We currently focus on repurposing the CRISPR system for transcriptional and epigenetic modulation of the genome. We aim to identify new factors and mechanisms that facilitate genome engineering, and initiate new approaches to prepare people for future efficient, safe, and responsible practices. A few examples of the previous or current projects:

  • ·       CRISPRi in bacteria (Cell 2013; Cell 2016; Nat. Protoc. 2013)
  • ·       CRISPRi in mammalian cells (Cell 2013; Cell 2014; Nat. Method. 2016) 
  • ·       CRISPR for genome imaging (Cell 2013)
  • ·       CRISPRi/a genome-wide screening (Cell 2014)
  • ·       CRISPR for synthetic biology (Cell 2015; Nat. Method. 2016)