Research Interest

Our lab is interested in building technologies that help answer fundamental biological questions. Below you'll see a few of our technologies and their applications.

 
 Guide+Donor  Our team has developed a strategy to generate thousands of yeast mutants, each with a defined genetic alteration (point mutation, deletion, or insertion) in a single reaction. We have also created a pipeline for simultaneously tracking the fitness of all of the resulting mutants  en masse . We are applying our technology to gain insights into the coding and non-coding portions of the genome, optimize metabolic pathways and better understand how point mutations influence protein structure and function.

Guide+Donor

Our team has developed a strategy to generate thousands of yeast mutants, each with a defined genetic alteration (point mutation, deletion, or insertion) in a single reaction. We have also created a pipeline for simultaneously tracking the fitness of all of the resulting mutants en masse. We are applying our technology to gain insights into the coding and non-coding portions of the genome, optimize metabolic pathways and better understand how point mutations influence protein structure and function.

 Synthetic gene drives  Gene drives are selfish genetic elements that "cheat" Mendelian inheritance. We were among the first to generate synthetic gene drives using Cas9. Our team is using this tool to perform rapid combinatorial knockouts within the clinically relevant fungal pathogen  Candida albicans,  along with exploring other exciting applications within yeast.

Synthetic gene drives

Gene drives are selfish genetic elements that "cheat" Mendelian inheritance. We were among the first to generate synthetic gene drives using Cas9. Our team is using this tool to perform rapid combinatorial knockouts within the clinically relevant fungal pathogen Candida albicans, along with exploring other exciting applications within yeast.

 DNA barcoded libraries  By employing DNA barcodes, we are able to track the growth of dozens of cellular models at a time. We use these pools of barcoded cells to perform multiplex screens aimed at understanding the genes involved in tolerance to misfolded proteins.

DNA barcoded libraries

By employing DNA barcodes, we are able to track the growth of dozens of cellular models at a time. We use these pools of barcoded cells to perform multiplex screens aimed at understanding the genes involved in tolerance to misfolded proteins.

 Truncated guides   We uncovered that Cas9 nuclease activity can be regulated by altering the length of the complexed gRNA. Using this knowledge we were able to perform simultaneous genome editing, gene activation and gene repression using a single Cas9 protein (Cas9-VPR). We plan to use this discovery to dissect the complex interplay between factors involved in adaptation to stress and drug resistance.

Truncated guides 

We uncovered that Cas9 nuclease activity can be regulated by altering the length of the complexed gRNA. Using this knowledge we were able to perform simultaneous genome editing, gene activation and gene repression using a single Cas9 protein (Cas9-VPR). We plan to use this discovery to dissect the complex interplay between factors involved in adaptation to stress and drug resistance.

 dCas9-KRAB-MeCP2  Through a series of engineering efforts we uncovered an improved dCas9-repressor, dCas9-KRAB-MeCP2. When used for single or multiplex gene repression it shows greatly enhanced activity versus previous tools. We are interested in using our repressor to identify drug sensitivities within tumor lines.

dCas9-KRAB-MeCP2

Through a series of engineering efforts we uncovered an improved dCas9-repressor, dCas9-KRAB-MeCP2. When used for single or multiplex gene repression it shows greatly enhanced activity versus previous tools. We are interested in using our repressor to identify drug sensitivities within tumor lines.

 dCas9-VPR  We created a second generation CRISPR-activator, which allows for potent gene activation across a variety of model organisms (human cells, mice, flies and yeast). We are currently using our activator for genome-wide screens and to study factors involved in cellular differentiation.

dCas9-VPR

We created a second generation CRISPR-activator, which allows for potent gene activation across a variety of model organisms (human cells, mice, flies and yeast). We are currently using our activator for genome-wide screens and to study factors involved in cellular differentiation.

 Tuned guide RNAs  We developed a system to endow Cas9 with single nucleotide specificity, through the development of tuned guide RNAs. With this method in hand we developed a "genomic surveillance system" which prevents cells from gaining undesired mutations. 

Tuned guide RNAs

We developed a system to endow Cas9 with single nucleotide specificity, through the development of tuned guide RNAs. With this method in hand we developed a "genomic surveillance system" which prevents cells from gaining undesired mutations.