Monday, April 28, 2025
4/28/2025
Development of Light Triggered Molecular Tools Critical for Understanding the Brain's Network - Development of Light Triggered Molecular Tools Critical for Understanding the Brain’s Network PI: Nasri Nesnas, PhD PROJECT SUMMARY Brain disorders, such as dementia, epilepsy, and depression, continue to be a major challenge in medicine. This is not surprising considering the enormous complexity of the brain’s network of neurons. An average human brain incorporates nearly 86 billion neurons intertwined with as many as 10,000 synaptic connections. Such complexity is far more colossal than any computer processor or even the entire worlds’ road maps. Therefore, brain-mapping efforts have become of apparent urgency to enable a better understanding of this complex maze. Making substantial advances in this area certainly requires collaboration of multiple disciplines. Light responsive molecular tools have become indispensible to neuroscientists as they provide means to manipulate specific neuronal connections with precise timing. We established collaborations with several neuroscientists, including Attila Losonczy of Columbia University to design and use these critical tools. They are investigating the role of calcium ions in learning and memory. We propose to develop molecular tools that can precisely modulate the concentration of calcium ions using photo switchable chelating systems. Photocleavable protecting groups, also known as cages, enable the release of active agonists with light. The principal advantage of this technique is the unparalleled precision of activation in location as well as timing, otherwise referred to as spatio-temporal control. We have prepared several of these cages, and we aim to design more efficient ones that can also respond in visible and near IR wavelengths to avoid photo toxicities associated with UV light traditionally used. Tamoxifen has been used as a ligand for inducing gene expression in Cre-ER Lox systems. We propose to prepare caged tamoxifen to enable our collaborator to use precise temporal control of gene expression in hippocampal cells. Preparation of effective photoactive molecular tools will directly benefit the larger neuroscience community in studying the brain with the level of detail essential to treating elusive brain disorders. I will continue to actively engage undergraduate students in these endeavors, and particularly emphasize the diversity of educational and cultural backgrounds of the members in my research lab. I have been successful at maintaining a larger percentage of female students than our university’s average and I will continue to do so as well as encouraging minority students to engage in research.
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