Mitochondrial Genetics: Mitochondrial genome engineering to unravel the genetic links between mitochondrial gene regulation and human disease for future mechanism-based therapies

Every cell in the human body carries a tiny second genome inside its mitochondria, the structures that convert food into energy, but scientists still cannot edit that DNA to find out what goes wrong in disease. Mitochondrial DNA contains genes essential for normal cell function, and mutations in it cause a range of inherited disorders that can affect muscles, brain, and heart. The problem is that the standard genetic tools used to study nuclear genes—such as cutting, replacing, or disabling DNA—do not work on mammalian mitochondrial DNA. Researchers also do not know the full set of genes that regulate mitochondria. This project aims to solve both problems: identify the unknown mitochondrial regulatory genes and develop the technology to engineer mitochondrial DNA directly. If successful, the work would give researchers a way to create precise cellular models of mitochondrial diseases, revealing exactly how each genetic defect disrupts energy production. That understanding is a necessary step toward designing therapies that target the root cause rather than just managing symptoms. Because the technology does not yet exist, this is fundamental science—building the tools first, before any clinical application can follow. Past breakthroughs in gene editing for nuclear DNA, for example, began the same way.