Using computational approaches to understand mitochondrial and nuclear interactions from genes to proteins.

11:00am

MRB 202 Conference Room

Emily A. Beck  (Assistant Professor, Molecular Biosciences, University of Kansas)

Mitochondrial function is essential for the maintenance of cellular health and relies on homeostasis between genomic elements encoded by two differently evolving and differently inherited genomes – the mitochondrial genome (mitogenome) and the nuclear genome. My lab is specifically focused on understanding how genomic variation both between and within individuals (heteroplasmy) impacts mito-nuclear physical and functional interactions. Mitochondria are essential organelles that play many important roles in cell signaling largely through maintenance of reactive oxygen species (ROS). ROS are naturally generated by mitochondria during energy production via Oxidative Phosphorylation (OXPHOS) using both mito and nuclear encoded proteins. At low levels, ROS is essential for maintenance of cell signaling, while at high levels ROS causes oxidative damage. Mitochondrial dysfunction can lead to oxidative stress through elevated production of ROS or under-clearance of ROS by inadequate antioxidant machinery. Mitochondrial dysfunction can also lead to antioxidative stress through reduced mitochondrial activity or overproduction of antioxidants by nuclear-encoded mitochondrial partners. Despite the unifying importance of mito-nuclear compatibility in maintaining Redox optimized ROS balance and preventing mitochondrial dysfunction, we still have several gaps in knowledge concerning how genomic variation in both mito and nuclear genomes impacts regulation of cellular health. Filling these gaps comes with technological challenges as we are unable to induce mitogenomic variation through genomic editing and inbred laboratory models lack the variation we need. My lab therefore turns to Evolutionary Mutant Models (EMMs) with evolved features that mimic something disease causing in humans but have evolved compensations that prevent disease. I use various computational genomic tools and protein structure prediction software to develop two unique animal models with evolved mitogenomic variation that allow us to study how nuclear genomes can support mitogenomic variation.