NSF Award
2200488
The Historically Black Colleges and Universities Undergraduate Program (HBCU-UP) through Research Initiation Awards provide support for junior and mid-career faculty at Historically Black Colleges and Universities who are building new research programs or redirecting and rebuilding existing research programs. It is expected that the award helps to further the faculty member's research capability and effectiveness and improve research and teaching at the home institution. This award to Fisk University provides an opportunity to develop tools that can detect dopamine with high spatiotemporal resolution, thereby enhancing the extent to which its impact on neural circuitry can be analyzed. Utilizing Caenorhabditis elegans (C. elegans) as a model organism, genetically encoded protein sensors and non-genetically encoded nanosensors will be developed, characterized, and used to investigate signaling mechanisms of cognitive function and animal behavior. This project also provides an opportunity to train undergraduate students, thereby contributing to the next generation of scientists who can contribute to scientific innovation, creativity, and productivity.<br/><br/>Dopamine (DA) is an important neurotransmitter involved in many different conserved signaling functions across the animal kingdom, including humans. Despite its well-known importance in processes including motor control, reward-motivated behaviors, and learning, there remains a dearth of tools to tracking DA levels or the activity of DA neurons in vivo. This project aims to develop DA biosensors in C. elegans that can precisely measure the spatiotemporal content of DA. Genetically encoded and synthetic DA biosensors will be developed to contain fluorescent components that will emit light upon the release of DA. After release of DA from presynaptic vesicles, DA will bind to the receptor and result an increase of florescent intensity. The synthetic DA nanosensors include a) single-walled carbon nanotube sensors (nIRCat) and b) carbon dot (CD) sensors. Binding of DA to nIRCat will increase its fluorescent intensity. Moreover, CDs will be used in combination with MnO2 nanosheets (NSs). CDs are naturally photoluminescence and can be quenched by MnO2 NSs. However, DA can transform MnO2 NSs into Mn2+ ions and result in the recovery of the photoluminescent signal. Florescent microscopy of the transgenic worm (dLight) and in the presence of synthetic biosensors, will enable dynamic tracking of DA in the live animal. These biosensors will be developed, optimized for C. elegans and their toxicity and efficiency will be investigated. Utilization of DA biosensors in combination with optogenetic manipulation of neuronal activity will support further inquiry on the spatiotemporal transmission of DA at the single cell level.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
