Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session I

25-POS Board 25 Combining Intravital Imaging and Gene Delivery to Better Understanding Protein Dysregulation, Degradation and Upregulation for the Generation of Improved Renal Therapeutics Peter R. Corridon 1,2 . 1 Australian College of Kuwait, Safat, Kuwait, 2 Indiana University School of Medicine, Indianapolis, IN, USA. Renal ischemic injury manifests in substantial protein dysregulation and degradation. Conventionally, there have been many limitations to improving the fundamental understanding of this diseased state. In vivo techniques, like two-photon intravital imaging, provide a unique platform to conduct such investigations with meaningful spatial and temporal resolutions. Using this approach, in conjunction with a novel hydrodynamic gene delivery technique, we were able to simultaneously investigate structural and functional changes that occur in the live rat kidney. Specifically, an effective use of hydrodynamic fluid forces has enabled efficient and reliable renal gene delivery that can overcome traditional hindrances to these investigations. By facilitating the expression of fluorescent actin, we were able to track this biomarker in normal in vivo conformations and modulations it undergoes during ischemic injury and repair. We also utilized this gene delivery technique to genetically alter the mitochondrial proteome. These alterations conferred with native enzyme upregulation that resulted in both the treatment of and protection against ischemic injury in the rat kidney. Overall, this novel and powerful combination of intravital imaging and gene delivery appears to be an exciting basis that can foster further biological advances in renal physiology.

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