Check out some of our recent work!
High-throughput recruitment of chromatin regulators
Human gene expression is regulated by thousands of proteins that interact with chromatin to activate or repress transcription. While some of these have been characterized individually in a low-throughput manner, we lack a broad understanding of which protein domains can modulate gene expression, how strong their effects are, and the dynamics of transcriptional memory after their recruitment. To systematically discover and characterize these dynamics of transcriptional regulatory domains, we have developed a high-throughput assay in which pooled libraries of protein domains are recruited to a reporter promoter and transcriptional effects are measured with a sequencing readout. This assay also allows us to perform deep mutational scanning of transcriptional regulatory domains, and more generally expand our toolbox of proteins we can use to perturb and modify the epigenome. Learn more about HT-recruit here!
Nanobody-mediated control of gene expression
Epigenetic editing tools are often made by engineering synthetic enzymes that contain both DNA binding domains and chromatin-modifying domains, overexpressing those enzymes in cells, and recruiting those enzymes to a locus or gene of interest. However, this overexpression process can often lead to cell toxicity and inadvertent changes to cell phenotype and behavior. We have developed a new tool to avoid these problems by using nanobodies to recruit endogenous chromatin regulators to a specific genomic locus for gene expression control; fusing these nanobodies to other chromatin regulators has also allowed us to improve the silencing and memory of those chromatin regulators. This gives us a foundation to continue building a toolbox of more efficient and less invasive tools to manipulate the epigenome. Read more about it here!