Cell-type specific manipulation of neural circuits is required for the treatment of neurological disorders such as epilepsy and Parkinson’s disease. Precise control of neural circuits will enable the development of neuromodulation therapies for these debilitating conditions. Existing technologies to control neural activity offer limited possibilities.

The nuclear envelope is a lipid bilayer that encases the genome and provides a physical boundary betweenthe cytoplasm and the nucleoplasm. While the nucleus is typically depicted as a sphere encircled by a smoothsurface of nuclear envelope, the smooth exterior can be interrupted by tubular invaginations of the nuclearenvelope into the deep nuclear interior. Such structures are termed the ?nucleoplasmic reticulum.?

Studies in the model eukaryote Saccharomyces cerevisiae have revealed that homologous recombination (HR) provides a major mechanism for eliminating DNA double-stranded breaks (DSBs) induced by ionizing radiation or are associated with injured DNA replication forks. During the repair process, the ends of the DNA breaks are resected nucleolytically to yield 3' ssDNA tails, which are bound by HR factors. The nucleoprotein complex thus formed then conducts a search to locate an undamaged DNA homolog, and catalyzes the formation of a DNA joint, called D-loop, with the homolog.

The long-term goal of this research project is to understand cellular, molecular, and epigenetic mechanisms ofendocannabinoid (eCB) signaling that may modulate synaptic and neurocognitive functions. While the eCBsystem is known to play an important role in regulation of brain homeostasis, accumulated informationsuggests that the eCB system is also involved in several mental and neurological disorders. Augmentation ofeCB signaling by inhibition of eCB metabolism has been proposed as a promising therapy for treatment andprevention of mental and neurocognitive illnesses.