Julia Joung (ZHANG LAB)

Genome-scale Activation of LncRNA Loci Identifies Novel Vemurafenib Resistance Mediators

Mammalian genomes transcribe thousands of lncRNAs, most of whose functions are unknown. We developed a CRISPR-Cas9 activation screen of >10,000 lncRNAs to identify noncoding loci that mediate BRAF inhibitor resistance in melanoma. We find 11 novel lncRNA loci, including one we term EMICERI. We functionally dissect the EMICERI locus to demonstrate that activation of EMICERI results in dosage-dependent activation of its four neighboring genes, including a kinase activator MOB3B, and that the resistance phenotype arises from MOB3B overexpression.

Ross Jones (WEISS LAB)

Understanding and Mitigating the Effects of Limiting Transcriptional Resources in Biological Systems

Synthetic biologists seek to design systems that can sense molecular inputs and actuate specific cellular outputs in response. However, scaling up the processing elements to handle increasing input and output complexity remains a major design challenge due to modularity breaking. This arises from unexpected or hidden interactions between molecular species, such as competition for limiting cellular resources. We apply control theory to biology with the aim of building new modules which can adapt to resource competition and mitigate its effects.