We have recently discovered a method by which functional mitochondria can be internalized by a specific cell type through receptor-mediated endocytosis, and replace damaged or absent mitochondria. Our previous studies were dependent on co-localization of complexed mitochondria and a targeted endosomolytic agent into the same endosomes in order to achieve endosomal escape of targeted mitochondria. We wondered whether covalent linkage of an endosomolytic agent directly to the targeting conjugate could increase the efficiency of mitochondrial internalization and escape.

The proposed project would include chemical linkage of a targetable carrier protein to a bacterial peptide, and preparation of an affinity chromatography system to purify the ternary conjugates. Using mitochondria from mouse cells as donors, and human hepatoma cells as recipients, uptake assays will be performed to test the new conjugates by confocal microscopy using fluorescent anti-mouse mitochondrial aby, and qPCR using primers specific for mouse mitochondrial DNA relative to human, LDHA chromosomal gene levels.

Preferred experience: labs in the above courses

Preferred interests: mammalian biology, biomedical engineering, translational biochemistry