APPROACH

We apply genetic, imaging, cell biological and biochemical approaches to identify mitochondrial pathways that control cell differentiation, development and inheritance. We use both fruit fly (Drosophila) and mammalian model systems.


HOW DEleterious MITOCHONDRIAl DNA mutations are eliminated

In most species, mitochondrial DNA (mtDNA) is inherited maternally, is subject to high mutation rates, and undergoes no recombination. This makes mtDNA susceptible to the accumulation of deleterious mutations, which can cause severe disease. Left unchecked, the increased genetic load would ultimately result in dysfunction of the mitochondria and the extinction of the species, via Muller’s ratchet. To prevent this, the female germline – the tissue that gives rise to eggs – has evolved a selection mechanism to purge itself of mutant mtDNA. Despite its fundamental biological importance, the mechanism underpinning mtDNA selection remains very poorly understood.

We harness the power of Drosophila genetics and advanced imaging to dissect the molecular mechanism of mtDNA selection.


HOW MITOCHONDRIA REGULATE STEM CELL DIFFERENTIATION

The differentiation of stem cells is a tightly regulated process essential to animal development and tissue homeostasis. We recently uncovered an essential and unexpected role for mitochondria in germline stem cell differentiation. Specifically, we found that during differentiation the inner mitochondrial membrane remodels, becoming highly invaginated and cristae dense, and that this is driven by an up-regulation of Complex V (also known as the ATP synthase). Unexpectedly, this requirement for mitochondrial remodeling during differentiation is independent of mitochondria’s canonical role in ATP production.

We use Drosophila genetics, imaging and human induced pluripotent stem cells to further elucidate the role mitochondria play in stem cell differentiation, function and fate.