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Aug. 19, 2022
Ranjan Dash, PhD, professor in the Marquette-MCW Joint Department of Biomedical Engineering, has received a $600,000 grant from the National Science Foundation for the project titled, “Advanced Ion Channel Modeling and Computational Tool with Application to Voltage-Dependent Anion Channel and Mitochondrial Model Development.” The project, done in collaboration with Dr. Dexuan Xie, professor of mathematical sciences at the University of Wisconsin—Milwaukee, seeks to fill a critical gap in the computational modeling of mitochondrial anion transport and function.
The voltage dependent anion channel (VDAC) is the most abundant protein on the outer mitochondrial membrane (OMM) and is the main conduit for simultaneous transport of ionic species into and out of a mitochondrion. Alteration of species transport across OMM can impact mitochondrial function and lead to disease pathologies. However, the current computational models of mitochondrial function do not account for species transport across OMM, and none of the current ion channel models work for VDAC on OMM in a mixture of many ionic species of different ion sizes.
This project aims to provide a nonlocal Poisson-Nernst-Planck-Fermi (NPNPF) ion channel model for VDAC, NPNPF finite element solvers and numerical schemes for computing ion channel electrostatics and kinetics based on 3D VDAC molecular structures, and the integrated VDAC-mitochondrial model.
This integrated model will be the first that can help identify the underlying molecular mechanisms that link microscopic VDAC electrostatics and macroscopic VDAC kinetics to mitochondrial function, and the results are expected to transform our understanding of how alterations of VDAC electrostatics and kinetics contribute to mitochondrial dysfunction and the pathogenesis of mitochondriopathic diseases. Mitochondriopathic diseases include autism spectrum disorder, heart, liver and kidney disease, and neurological diseases such as seizures.
This project is an expansion of Dr. Dash’s computational modeling investigations into metabolic processes and their effects on integrated mitochondrial functions and dysfunctions in health and disease.