Kansas State University

NIH Research Projects · FY 2025 · 2017-07

PROJECT SUMMARY: OVERALL The goal of this Phase 2 COBRE application is to continue to develop a unique, nationally recognized, thematic research center on Cognitive and Neurobiological Approaches to Plasticity (CNAP). We will build on Phase 1 successes by further enhancing research infrastructure and continuing to build a critical mass of investigators studying cognitive and neural plasticity. We will continue to develop the plasticity thematic focus of the center by supporting research in three new cross-cutting thematic areas: The Neurobiology of Learning and Memory, Neuromodulation and Assessment, and Advanced Computational Modeling. The cross-cutting themes bridge across animal models and human translational research, and across disciplines. The cross- cutting themes reflect the planned enhancements of the research cores, knit together the current projects, will guide priorities for faculty recruitment and future pilot grant and replacement project grant selection, and will inform future program development initiatives. Further development of the CNAP center and its associated programs will propel us toward achieving our goal of improving cognitive and neural functioning in both healthy populations and in individuals with specific diseases or disorders. CNAP center development will be advanced through the achievement of four specific aims: (1) To promote R01 award success for CNAP project and pilot grant leaders. In Phase 2, we will support three new research project leaders who have strong potential to transition to R01-level support. In addition, following the success of our active pilot grant program in Phase 1, we will continue to fund pilot grants annually in Years 2-5, providing further opportunities for graduation of junior investigators to R01-level research support. (2) To continue to develop a critical mass of researchers in cognitive/neural plasticity through recruitment of new CNAP members. We will recruit three new tenure-track faculty in research areas relevant to the CNAP cross-cutting themes. We will further expand CNAP membership by funding new pilot grants and expanding the research cores. (3) To further improve research infrastructure by expanding three multi-user core laboratory facilities. We will expand the Behavioral Neuroscience Core, Cognitive Neuroscience Core, and Neuroinformatics Core by adding significant new capabilities to promote access to modern neuroscience and computational modeling techniques. (4) To enhance the research capabilities of CNAP center members through strengthening the Scientific Exchange Network (SEN). The SEN will provide CNAP researchers access to additional core facilities and training to increase their capability to secure extramural funding. Achieving these aims will further advance a thriving thematic research center that will increase the understanding of cognitive and neural mechanisms of plasticity. CNAP will attract extramural funding through individual investigator and partnership grants, will promote a rich research climate for fostering investigator development, will continue to enhance research infrastructure, and will provide a pathway to long-term center sustainability by the end of Phase 3.

NIH Research Projects · FY 2026 · 2012-08

PROJECT SUMMARY The inability to remove protein aggregates in non-dividing cells such as neurons or muscles is a key factor in the development and progression of neurodegenerative diseases and myopathies and is a cellular hallmark of aging cells. While protein aggregate diseases share common features, the molecular pathways that lead to abnormal protein accumulation cannot be explained by a single mechanism. In protein aggregation diseases that affect skeletal and cardiac muscles, a general trend has emerged in which aggregated proteins and organelles accumulate in regions devoid of sarcomeric proteins. However, the cellular and mechanical triggers that initiate Z-disk disintegration and myofiber displacement are unclear. Here we employ mutations in conserved Drosophila genes as an entry point to uncover cellular and molecular mechanisms that lead to protein aggregation and ultimately cellular degeneration using muscle as a model cell type. Overall, we expect to uncover new proteins that contribute to proteostasis; identify muscle targets of kinase activity; and define how mechanical tension and autophagy cooperate in the clearance of protein aggregates. A powerful combination of genetic analysis, biochemistry, cell biology, and optogenetic approaches will address these questions. We expect that this project will fundamentally advance our understanding of how protein degradation is regulated to prevent cellular degeneration and provide fresh insights into how protein aggregates can be effectively cleared to reduce disease states.