The rockefeller university

Cori is the Torsten N. Wiesel Professor and Head of the Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior at The Rockefeller University and Head of Science at the Chan Zuckerberg Initiative. She studies the neuronal basis of behavior in C. elegans, an animal whose small nervous system and powerful genetics provide unique opportunities to characterize genes, neurons, and circuits at multiple levels of analysis. By examining circuits for olfactory behavior, social behavior, and foraging behavior, using both natural genetic variation and induced behavioral mutants, she asks how genes and the environment interact to generate flexible behaviors. This work has revealed elements of innate behaviors that share principles and molecular mechanisms across animal species.

As a graduate student with Robert Weinberg at MIT, Cori cloned the neu oncogene, and demonstrated that it encodes a receptor tyrosine kinase protein related to the EGF receptor that is mutated in rat neuro- and glioblastomas. Subsequent work from Mark Greene, Dennis Slamon, and Genentech showed that neu (also called HER2) is amplified in human breast cancer, leading to the development of the antibody Herceptin, a drug directly targeted to a genetic lesion in human cancer.

After discovering that the nematode worm C. elegans has a sense of smell when she was postdoc with Bob Horvitz at MIT, she moved to UCSF where her lab addressed the molecular and cellular logic of olfaction. Work from her lab provided the formal proof that G protein-coupled receptors detect odors by defining a single olfactory receptor gene, odr-10, that allows C. elegans to detect a specific odor ligand. By genetic manipulation of ODR-10, Cori and colleagues showed that olfaction in C. elegans uses a “labeled line” logic in which sensory neurons are innately coupled to attractive or aversive behaviors. This logic has subsequently been shown to apply to mammalian taste and somatosensation.

Cori moved to the Rockefeller University in 2004, where her lab continued its genetic analysis of the nervous system’s development and function. Although the lab uncovered fascinating molecular and cellular mechanisms of axon guidance and synaptic connectivity, they realized that the connectome does not explain all of behavior. This point emerged forcefully from their genetic studies of natural variation in social and foraging behaviors, where they mapped interesting behavioral traits and discovered that these traits affected not the classical connectome, but neuromodulatory systems. Neuromodulation also plays a central role in learning that can adaptively respecify innate responses, like food and odor preferences. Cori’s work indicates that neuromodulators define a “wireless” communication network that is superimposed on the classical wiring diagram, but with an orthogonal logic and slower dynamics. This work sheds light on the fast, flexible remodeling of behaviors over time, an important but elusive aspect of nervous system function.