Recent evidence indicates that there exist locations in the adult brain that constantly generate new cells that migrate into specific regions involved in olfaction, memory and learning. This project aims to provide new information regarding the mechanisms that are responsible for this important and complex process. The PI also plans to use this knowledge to bioengineer structures which, when implanted into brain, will form new migratory paths that will deliberately target new neurons into specific regions of the brain. When delivered to areas impacted by injury or disease, these new neurons are anticipated to restore lost function.
During adult neurogenesis, a large number of molecules participate in complex signaling, which requires precise spatial and temporal control. Although several of these neurotrophic ligands and cognate receptors have been identified, many questions remain regarding the molecular mechanisms by which these components function. The goals of this project are to characterize the mechanism by which specific factors mediate neurogenesis using an in vitro system and then use this information to bioengineer cylindrical fibrin-based implants which will generate new neural migratory paths in vivo. The project involves in vitro and complementary in vivo aims. The premise of the in vitro studies is that neural stem cells receive neurotrophic signals in a particular order and one role of each ligand is to induce the expression of the receptor for the next ligand. The in vivo experiments will exploit novel, readily bioengineered fibrin cylinders that will be implanted into the brain in order to recruit endogenous neural progenitor cells from their usual niche and target them into non-neurogenic regions. The project will use time-lapse microscopy, fluorescence microscopy, immunochemistry, and animal behavioral studies to accomplish the aims. Undergraduate researchers will participate in this research through a program dubbed FIRE (Full Immersion Research Experience), where the students will be involved in all aspects of a research program, including literature evaluation, grant writing, technical and presentation skill development, and preparation for graduate school application.
