Pharmacogenomic discovery of genetically targeted cancer therapies optimized against clinical outcomes.

Despite the clinical success of dozens of genetically targeted cancer therapies, the vast majority of patients with tumors caused by loss-of-function (LoF) mutations do not have access to these treatments. This is primarily due to the challenge of developing a drug that treats a disease caused by the absence of a protein target. The success of PARP inhibitors has solidified synthetic lethality (SL) as a means to overcome this obstacle.

Bright split red fluorescent proteins for the visualization of endogenous proteins and synapses.

Self-associating split fluorescent proteins (FPs) are split FPs whose two fragments spontaneously associate to form a functional FP. They have been widely used for labeling proteins, scaffolding protein assembly and detecting cell-cell contacts. Recently developments have expanded the palette of self-associating split FPs beyond the original split GFP.

The receptor protein tyrosine phosphatase CLR-1 is required for synaptic partner recognition.

During neural circuit formation, most axons are guided to complex environments, coming into contact with multiple potential synaptic partners. However, it is critical that they recognize specific neurons with which to form synapses. Here, we utilize the split GFP-based marker Neuroligin-1 GFP Reconstitution Across Synaptic Partners (NLG-1 GRASP) to visualize specific synapses in live animals, and a circuit-specific behavioral assay to probe circuit function.

avoids toxin-producing using a seven transmembrane domain chemosensory receptor.

Predators and prey co-evolve, each maximizing their own fitness, but the effects of predator-prey interactions on cellular and molecular machinery are poorly understood. Here, we study this process using the predator and the bacterial prey which have evolved a powerful defense: the production of nematicides. We demonstrate that upon exposure to at their head or tail, nematodes display an escape response that is mediated by bacterially produced cues.