Friday, May 9, 2025
5/9/2025
New Methodologies for Connectomics - PROJECT ABSTRACT The nervous systems of animals are comprised of neurons connected by a large number of synapses. The resulting neural networks underlie animal behavior and contribute to the storage of learned information in many species. In humans, the miswiring of neural networks likely results in disorders of behavior, learning, and thought. For all these reasons, understanding the development, organization, and disruptions in neural circuits is vital. The goal of connectomics is to produce and study the maps of neuronal connections within nervous systems. Connectomic research requires automated image acquisition of brain tissue images that cover large volumes at high magnification to resolve synapses and methods to generate wiring diagrams from these images. But the connectivity map itself is nevertheless not sufficient to explain the brain functions. Additional information, such as the molecular identity of neurons, needs to be extracted from the same nervous system. The primary goal of this proposal is to develop the heavy metal staining of whole mouse brains and other large brain samples for volumetric electron microscopic mapping of a full connectome (Aim1), generate a library of miniaturized protein binders for correlated light and electron microscopic imaging to bridge connectomics with neuronal cell type studies (Aim2), and expand the use of X-ray microscopy in multiplexed brain imaging (Aim3). These studies will lay the foundation for the development of connectomics and establish new paradigms for multimodal imaging. My career goal is to run an academic lab that develops essential methodologies for brain research. The proposed work that focuses on the most urgent needs of connectomics will become a mainstay for my independent research and allow me to integrate the newly acquired knowledge in neurobiology, biochemistry, and microscopy with my interdisciplinary training in chemistry and materials science. The unique environment at Lichtman lab will put me in a privileged position in order to pursue my career aspirations. I have developed a detailed training plan with my mentor, Prof. Jeff Lichtman, to help me transition to independence. I will meet regularly with him to discuss research progress, strategies for grant writing, student mentorship, and lab management. I will oversee the work of a graduate student to practice my mentorship skills. To broaden my scientific network and establish future collaborations, I will present my work in workshops, connectomics meetings, SfN and ACS annual meetings. As a member of the Harvard Department of Molecular and Cellular Biology, I will have access to leaders in neuroscience, molecular biology, cell biology, and biochemistry, as well as cutting-edge core facilities. The BRAIN Initiative Diversity K99/R00 will provide me the funding required to initiate an ambitious research plan to tackle the outstanding challenges surrounding brain studies.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).