James Eberwine, PhD
PHILADELPHIA— James Eberwine, PhD, the Elmer Holmes Bobst Professor of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine at the University of Pennsylvania, is part of an international team of researchers, who will receive $1.25M over the next three years to better understand oxidative phosphorylation (OxPhos), a biological system that plays a key role in the production of energy, generation of free radicals, and cell death.
The funding, one of 23 grants globally selected from 770 applications, is provided by the International Human Frontier Science Program Organization, which supports research on complex mechanisms in living organisms by fostering collaboration between scientists in different countries and specialties.
Under the grant, Eberwine and colleagues from Spain, Germany, and Switzerland will ask if organisms have evolved mechanisms to ensure the expression of defined groups of genes to avoid functional conflict between alternative protein variants.
OxPhos is the only process in animal cells that requires components encoded by two genomes: the mitochondrial DNA inherited through the mother and the nuclear DNA inherited from the mother and father. (Mitochondria produce about 90 percent of the chemical energy that cells need to survive.) As a result of this interaction, instead of the usual expression of genes from both parents, genes are expressed from just one parent. Eberwine and his colleagues will examine the mechanisms that enable such gene expression to coexist in cells.
To do this, they will use several strategies and techniques: RNA sequencing and gene expression analysis in individual cells to determine if one or the other allele is expressed; fluorescence microscopy in zebrafish to monitor tagged proteins produced by one or the other allele; and analysis of how these findings relate to mitochondrial function in specific mouse and zebrafish lines.
In addition to Eberwine, other members of the research team are José Antonio Enríquez, PhD, of Centro Nacional de Investigaciones Cardiovasculares Carlos III in Madrid; Karin Busch, PhD, of the Cell and Molecular Biology Institute at the University of Münster; and Nadia Mercader, PhD, of the Anatomy Institute at the University of Bern.
In issuing the award, the International Human Frontier Science Program Organization described the project as “hold[ing] the potential to generate results that may have truly transformative power and ... the knowledge gained will significantly improve our understanding of basic biological mechanisms.”
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