Meital Oren-Suissa earned her BSc in molecular biochemistry, cum laude (2003), her MSc in Biology, cum laude (2006), and her PhD in Biology (2012) all from the Technion—Israel Institute of Technology. She completed her doctoral studies on the mechanisms of neuronal branching under the guidance of Prof. Benjamin Podbilewicz. Her postdoctoral training at Columbia University at the lab of Olive Hobert focused on sex differences in neuronal wiring patterns during development. She joined the Weizmann Institute of Science in July 2017. Her lab studies the development of neuronal circuits that control behaviors that differ between males and females. Meital and her team recently discovered that sexually-dimorphic circuits are controlled by synaptic protein degradation. These findings provide insight into the mechanisms that generate sex-specific differences in neuronal connectivity, activity and behavior.
Meital’s research is supported by the European Research Council (ERC Starting Grant), the Israel Science foundation, the Minerva Stiftung foundation and by the Azrieli foundation (early career faculty fellowship).
Sexual dimorphisms in brain structure and function are evident across phylogeny, but little is known about sexually dimorphic features of individual neurons, and the mechanisms for establishment and maintenance of dimorphic neuronal circuits. My lab investigates how sexually dimorphic patterns in the brain emerge, from synapse formation to animal behavior.
We have recently demonstrated the involvement of the ubiquitin-proteasome system (UPS) in sex-specific synapse pruning. We found that the UPS promotes degradation of the netrin receptor DCC/UNC-40 in a particular neuron only in one sex, leading to sex-specific patterns of synaptic connections. Our results demonstrate that UPS pathways have the potential to reconfigure the nervous system via synapse elimination in a spatial and temporal manner, and to accommodate the need for sex-specific circuit structure and function. Building on these results, we are currently i) investigating the role of DCC/UNC-40 in synapse stabilization, organization and maintenance ii) studying the role of UNC-40 in dopaminergic neurons during health and disease.
In parallel, we seek to elucidate how genetic sex modulates circuit dynamics. The underlying mechanisms can only be currently resolved in C. elegans, where the connectome of the nervous system for both sexes has been mapped. Using technologies such as optogenetics, calcium imaging, trans-synaptic labeling and single-cell transcriptome analysis we reveal a significant difference in the way the two sexes respond to nociceptive stimuli. Detailed circuit analysis reveals that the neuronal dynamics and connectivity of sex-shared neurons are shaped by their sexual identity to define the activity of circuits and ultimately, of behavior.