Current Research Projects

Sex differences in Neural Development, Circuit Function and Behavior

The biological sex of an organism has profound consequences on its development and physiology. The mechanisms underlying these sex differences have particular relevance for the strong sex bias associated with many neurological and mental health disorders, including autism, anxiety disorders and Tourette syndrome. The Portman laboratory explores the intersection between biological sex and neurobiology using the nematode C. elegans, a simple and tractable invertebrate model whose study has made numerous contributions to understanding mechanisms of neural development and function. We have a particular interest in the means by which chromosomal sex modulates both the architecture and function of the nervous system. In three related projects, we are taking a multifaceted approach, using genetics, genomics and behavioral analysis, to study this problem with bottom-up and top-down approaches. Because core components of the sexual differentiation machinery are conserved from nematodes to mammals, our research is likely to shed light on genetic networks and cellular mechanisms that regulate susceptibility to a variety of neurological and mental health disorders.

Projects

1. Project I: Cell fate specification in the developing nervous system (Supported by NIH R01 NS050268)

   • Define the mechanisms by which Wnt-mediated asymmetric segregation of the MATH5/atonal homolog LIN-32 patterns the neuroglial progeny of a male-specific neural precursor cell
   • Determine the roles of the conserved DMRT/doublesex-family gene dmd-3 in effecting sex differences in a simple sensory cell lineage
   • Molecularly identify new genes required for specification and differentiation during sex-specific neurogenesis

2. Project II: Genetic control of sex differences in the nervous system (Supported by NIH R01 GM086456)

   • Characterize the extent of sex differences in C. elegans olfaction, a shared sensory behavior mediated by a simple neural circuit
   • Determine the molecular mechanism by which the function of the shared AWA neuron pair is regulated by sexual differentiation
   • Use genomic approaches to define the extent of sexually dimorphic gene expression in shared C. elegans sensory neurons

3. Project III: Sexual modulation of C. elegans locomotor behavior (Supported by NSF IOS-0920024)

   • Rigorously quantitate sex differences in waveform and kinetics of locomotor behavior in larval and adult nematodes
   • Using genetic sex-reversal of specific cell types and subtypes, define the contribution of sexual differentiation of neurons, muscle, and hypodermis to modulation of motor function
   • Elucidate the molecular mechanisms by which sexual differentiation impinges on specific aspects of neurotransmission to regulate sex differences in motor behavior