Dr. Ranjan Dash Awarded NSF Grant for Development of Advanced Ion Channel Modeling and Computational Tool with Application to Voltage-Dependent Anion Channel and Mitochondrial Model
Marquette-老澳门六合彩图库 Joint Department of Biomedical Engineering faculty Dr. Ranjan Dash, in collaboration with Dr. Dexuan Xie, Professor of Mathematical Sciences at the University of Wisconsin–Milwaukee, 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 seeks to fill a critical gap in the canon of computational modeling of mitochondrial function by considering the largely neglected anion transport via the voltage dependent anion channel (VDAC) across the outer mitochondrial membrane (OMM) to elucidate the mechanisms by which anion transport via VDAC across OMM impacts mitochondrial function.
The VDAC is the most abundant protein on the OMM and is the main conduit for simultaneous transport of ionic species into and out of a mitochondrion. Alteration of species transport across OMM via VDAC can impact mitochondrial function leading to disease pathologies. However, the current computational models of mitochondrial function do not account for any species transport across OMM via VDAC, and none of the current ion channel models work for VDAC on OMM in a mixture of many ionic species of different ion sizes.
The NSF funded project seeks 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, as well as an integrated VDAC-mitochondrial computational model. This integrated model will be the first that can elucidate 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.
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. For more information on this or other projects underway in the Computational Systems Biology Laboratory, please contact Dr. Ranjan Dash (rdash@mcw.edu).