Researchers in the Graham Lab have used the Sucla2 mutant ES clone to generate a transgenic line and mutant embryos exhibit mtDNA depletion and mitochondrial dysfunction in brain and muscle. Researchers here are currently using conditional knockout and conditional genetic rescue strategies to bypass late embryonic lethality and to study SCS deficiency in adult animals. The team is also developing and studying gene trap mutants for select components of respiratory chain complexes I, II, and V.
Voltage-Dependent Anion Channels (VDACs or mitochondrial porins) are a family of proteins present in the mitochondrial outer membrane that play a critical role in the regulation of outer membrane permeability. Porin is the predominant VDAC in Drosophila. The Graham Lab has generated and been studying hypomorphic mutants of porin. These mutants exhibit defects in energy metabolism, male fertility, and neuromuscular and synaptic function. The lab team has performed genetic screens for suppressors of mutant porin phenotypes and are working to identify candidate suppressor loci.