Research
We develop highly multiplexed CRISPR/Cas-based technologies for precision genome engineering in microbes.
Research in the lab combines development of cutting-edge genome editing technologies with applications that advance our understanding of how genotype determines phenotype. By providing a direct link between sequence and function, at unprecedented scale, these tools allow us to gain principally new insights into how subtle genome variation impacts phenotype and enable massively scaled screens to accelerate construction of designer strains in biotechnology and synthetic biology.
High-throughput CRISPR-based genome perturbation
We develop CRISPR technologies for massively parallel precision genome perturbation and direct functional screening in microbes. These build on our platform MAGESTIC (Multiplexed Accurate Genome Editing with Short, Trackable, Integrated Cellular barcodes), which can engineer thousands of defined mutations in parallel in a single test tube. MAGESTIC uses pools of array-synthesized oligos encoding a gRNA and a donor DNA to introduce a designed mutation. Importantly, strains are tagged by DNA barcodes, allowing to efficiently track mutations in cell populations during functional screens and read out mutation identities via barcode sequencing.
Applying precision editing to study how genotype impacts phenotype
We apply our tools to study how genetic differences between individuals impact variation in phenotype, using yeast as a model system. A particular interest is to study how mutations that do not alter a protein's amino acid sequence alter its expression and function, and how different contexts alter the impact of a mutation. Using our tools we can also efficiently design, engineer and screen large libraries of mutants for advantageous properties for industrial and medical applications.