"Patrick" Yizhi CaiView all speakers
“Patrick” Yizhi Cai received a bachelor degree in Computer Science in China, a master degree in Bioinformatics from University of Edinburgh in the UK, and a PhD in Genetics, Bioinformatics and Computational Biology from Virginia Tech in the USA. Cai has his postdoctoral fellowship under Jef Boeke in the Johns Hopkins University School of Medicine. Cai serves as a senior scientific consultant to Beijing Genomics Institute, and is the first Autodesk Distinguished Scholar.
Starting summer 2013, Cai will start his own research group at the University of Edinburgh with a prestigious Chancellor’s Fellowship, and his lab focus on Computer Assisted Design for Synthetic Biology, NeoChromosome design and synthesis in the yeast, and DNA assembly automation.
We propose a Gene Guard approach, “K-plex Integrated Safety Switches (KISS)”, rooted in the development of foundational genomic, regulatory and metabolic technologies. To demonstrate the generality of our approach and the prospect of extending safeguards to any microorganism, we present the coordinated development of KISS in both Escherichia coli and Saccharomyces cerevisiae, the best studied model prokaryote and eukaryote microorganisms, with natural and synthetic genomes. This combined approach assures the development of generic strategies for a wide range of microbes, and many aspects of it are even compatible with viruses. We designed five main KISS “SafeGuard Technologies” that act at the genetic, transcriptional, translational and metabolic levels, enabling us to deploy multiple GeneGuards for safety and isolation. By targeting different cellular processes in a multiplex fashion, our approach enables us to generically affect the function of one or more genes, nutrients or metabolites essential to microorganisms. Importantly, these SafeGuard Technologies can act individually or in any combination for multiplicative effectiveness. For example, engineered protein and/or RNA-based switches can be used to replace native regulatory mechanisms such that cell viability can be specifically linked to the presence of exogenous synthetic small molecules. Because any of hundreds of essential gene(s) can be re-engineered in this manner, we could increase the effectiveness of such a safety switch by multiplexing essential genes (e.g., histone genes in S. cerevisiae; guanylate and thymidylate kinase genes in E. coli and S. cerevisiae). The strong selections in place for essential gene function (viability) will allow assessment of the development of resistance to KISS to be rapidly assessed. If resistance is observed, mechanism(s) of resistance will be assessed. The nature of the design is such that it can readily be adapted to any microbe, multicellular organism or even viruses, any organism with one or more essential genes.