Dr. George Wu
Undergraduate Research Opportunity Description
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.
|Project Direction||Mammalian cells cannot survive without mitochondria, and there are many genetic and acquired diseases known to be caused by defects in mitochondria. Most of these diseases are either lethal or result in a shortened life span and dysfunctional organs, especially liver because of its role in intermediary metabolism and detoxification. At present, aside from liver transplantation, there is no way to reverse damage to liver mitochondria or replace them. The current invention is envisioned to take advantage of the presence of unique receptors on the surface of mammalian liver cells that might permit targeted replacement of liver mitochondria instead of surgical replacement of liver.|
|Mentorship and Supervision||We will have an initial meeting to discuss the project, tour the lab and meet other members of the research team. The student will work with our research assistant and post-docs to learn methods and techniques. The student will present data at weekly lab meetings to review data, and solve problems. We will meet separately, at least once a week, usually after lab meetings to provide evaluation, and feedback.|
|Student Qualifications||Required courses: biochemistry, cell biology, molecular biology
Preferred experience: labs in the above courses
Preferred interests: mammalian biology, biomedical engineering, translational biochemistry
|Summer Schedule Options||Research Dates: 9-10 full-time weeks to be scheduled between June 7 and August 25, 2017
Schedule: To be determined in consultation with the selected students, within the parameters of M-F, 7am-6pm
|Project Continuation||Fall 2017, Spring 2018|
|Academic Year Time Commitment||9 hours/week|
|Possible Thesis Project||Yes|
Submit an online application for this research opportunity using the form below. The application deadline is Friday, February 24, 2017.
This application requires a cover letter, a resume or CV, an unofficial transcript, a brief statement of research interests, and a brief statement of career interests.