Our
Research
We study sex differences in the nematode C. elegans
to understand how genes shape neural circuits
— and how neural circuits shape behavior.
Biological sex is a fundamental variable in the development and function of the nervous system. Across species, sex differences in behavior and brain function can reveal how genetic programs can produce flexibility within conserved neural circuits. In humans, many neurological and neuropsychiatric disorders differ by sex in incidence or severity, raising the possibility that sex-based mechanisms of susceptibility or resilience could inform new strategies for prevention, diagnosis, and treatment.
We use the nematode C. elegans to study how biological sex shapes neural circuit function and behavior. The compact and fully mapped nervous system of C. elegans enables mechanistic dissection of these processes at cellular and molecular resolution. The two sexes of this species, males and hermaphrodites, differ dramatically in their behaviors and life strategies — for example, hermaphrodites prioritize feeding, while males will abandon food in search of mates. We and others have found that many of these behavioral differences arise not from dedicated sex-specific circuits, but from the sex-dependent modulation of neurons and circuits shared by both sexes.
An important finding from our work is that that biological sex can reconfigure the physiology of sex-shared neurons to optimize behavior in a sex-specific context. This modulation occurs at multiple levels: it can reshape sensory tuning to prioritize detection of sex- or context-relevant sensory cues (such as food or pheromones), and it can reorganize neuromodulatory pathways that govern behavioral states and prioritization.
Our current work focuses on two related problems. First, we are working to identify molecular pathways and cellular mechanisms through which sex, developmental stage, and physiological state converge to regulate shared neural circuits. Second, we seek to understand how and why targeting certain regulatory nodes — e.g., sensory neurons and neuromodulators — enables adaptive sex differences in behavior. Our studies provide a framework for dissecting how multiple dimensions of internal state are integrated at the level of individual neurons to produce adaptive behavioral variation — a problem at the heart of both evolutionary neurobiology and human brain health.