Differences in gene expression among tissues and cell types are responsible for phenotypic diversity. Regulatory elements, such as promoters and enhancers, are DNA sequences that bind transcription factor proteins in order to regulate the expression of a gene. A current challenge in understanding the networks that govern gene regulation is associating putative regulatory elements with specific genes. CRISPR-Cas9 is a tool that can functionally associate regulatory elements with genes through site specific transcriptional regulation. We are using CRISPR-Cas9 to cleave the seven putatively identified enhancers of the proto-oncogene, MYC. MYC is an essential transcriptional regulator involved in cell proliferation. By using CRISPR-Cas9 to cut the putative enhancers of MYC and measuring the effect these perturbations have on cell viability, we can better understand the regulatory network for a complex proto-oncogene, as well as develop a scalable method to elucidate enhancer connectivity to be used throughout the genome.
PROJECT: CRISPR-Cas9 as a tool to study promoter-enhancer interactions in MYC
Participating in SRPG and working at the Broad reminded me of the importance of challenging myself, both intellectually and personally. Asking ambitious questions and questioning the status quo are paramount. No topic is too big to pursue, and this intellectual freedom has expanded the way I approach and tackle new problems.