Department of Biochemistry
and Molecular Biology

Postdoctoral fellowship, Carnegie Institution, Department of Embryology, Baltimore, MD
Ph.D., Curriculum in Genetics and Molecular Biology, University of North Carolina - Chapel Hill, Chapel Hill, NC
B.A., University of Pennsylvania, Philadelphia, PA

• Back to faculty profiles
• PubMed listing

Research interests

Background

Mitochondria are cellular organelles that produce the majority of ATP in eukaryotic cells. Historically, they have been intensively studied biochemically, and many of the metabolic pathways that take place in mitochondria, such as the TCA cycle and electron-transfer, are well characterized. Mitochondria are unique in that they contain their own DNA, mtDNA. While this DNA is small, approximately 16kb in metazoans, it is critical for normal mitochondrial function. Because mitochondria cannot be made de novo, all of your mitochondria and mtDNA were inherited from your mother’s oocyte cytoplasm.

In the last twenty years, an increasing number of diseases have been linked to mutations in either mtDNA or nuclear genes encoding mitochondrial proteins. While the general observation that faulty mitochondria can lead to disease may not be surprising given the important role mitochondria play in cellular function, the specificity with which only certain cell types are affected by single mutations has been. In addition, there is mounting evidence for a role of mitochondrial dysfunction in common diseases, such as neurodegenerative disease and diabetes.

In the past decade or so, a previously under-appreciated aspect of mitochondrial biology has come to light. Mitochondria are not simply static ATP-producing machines (the so-called "power house of the cell"), but are instead very dynamic. They change shape and size due to growth and fission/fusion, and mitochondria can rapidly transit around the cell by moving along the actin and microtubule cytoskeleton.

The broad interests in my lab are studying how mitochondria change shape, location physiology and mtDNA content in response to developmental changes, and elucidating which genes and pathways are responsible. To address these general questions, we use the model system Drosophila melanogaster, or fruit fly. The advantages to using fruit flies are that they have a rich genetic history, allowing rapid and straightforward mutant acquisition, researchers understand much about organ and tissue development, and mitochondria can be imaged in fixed and live tissue at single organelle resolution. While fruit flies are interesting in and of themselves, it is important to note that an estimated 75% of human disease genes have a functional homolog in flies. The overwhelming similarity of genes and molecular pathways between humans and flies allows researchers to apply knowledge gained from Drosophila to elucidate the causes of human disease.

Understanding mitochondrial inheritance

mtDNA has a higher mutation rate than nuclear DNA and mitochondria are maternally inherited. Despite this, females can reproducibly and reliably produce hardy offspring. We are interested in identifying the genes and mechanisms involved in ensuring the mother deposits only highly functional mitochondria into the oocyte in order to support embryonic development. We can clearly visualize mitochondria during all of oogenesis in both fixed and live tissue and we have characterized several genes involved in normal mitochondrial function in the ovary. Mitochondria exhibit stereotypical changes during oogenesis (for one example, see image below), thus mutations that perturb mitochondrial localization or function can be readily identified.



The gene we are currently studying, clueless, is involved in mitochondrial localization and function. Flies mutant for clu are sterile, uncoordinated and have reduced life-spans. In clu mutant ovaries, mitochondria are distinctly mislocalized to the plus-end of microtubules. Clu protein is highly conserved and present in particles in the germline.

  

We believe clu acts to maintain mitochondrial function. When absent, mitochondria accumulate damage and subsequently undergo directed movement to the plus-ends of microtubules.

Selected publications

Cox, R. T. and Spradling, A. C. (2009) clueless, a conserved Drosophila gene required for mitochondrial subcellular localization, genetically interacts with parkin. Disease Models & Mechanisms, 2(9/10): 490-499.

Cox, R. T. and Spradling, A. C. (2006) Milton controls early mitochondrial acquisition by the oocyte. Development 133: 3371-3377.

Cox, R. T. and Spradling, A. C. (2003) A Balbiani body and the fusome mediate mitochondrial inheritance during Drosophila oogenesis. Development 130:1579-1590.

PubMed listing: http://www.ncbi.nlm.nih.gov/pubmed?term=cox%20rt%20drosophila

About Uniformed Services University

Uniformed Services University offers post-baccalaureate education in the health sciences. USU is located in Bethesda, Maryland on the beautiful green campus of the National Navy Medical Center (to be renamed Walter Reed National Military Medical Center in 2011). We are across Wisconsin Avenue (aka Rockville Pike) from the National Institutes of Health and the D.C. METRO’s red line Medical Center stop. The F. Edward Hébert School of Medicine is found within USU. The School of Medicine has three graduate programs: Molecular and Cellular Biology, Emerging Infectious Disease, and Neuroscience. These programs are PhD granting and like most graduate programs, are civilian and do not require any military commitment. If you are interested in learning more about graduate education at USU, visit http://www.usuhs.mil/graded/. The School of Medicine provides the Nation with healthcare professionals who are dedicated to careers in the military. These men and women receive specialized military medical training in addition to our standard medical school curriculum. If you are interested in learning more about medical education at USU, visit http://www.usuhs.mil/prospectivestudents.html.

Graduate students

We welcome inquiries from matriculating graduate students interested in rotations. Our lab uses a combination of confocal microscopy, molecular biology, biochemistry and genetics to study cell and developmental biology. We examine several aspects of fly development, including the ovary, testes and brain. Our system is well suited for rotation projects.

The faculty in the Department of Biochemistry are interested in recruiting graduate students to their labs.

top...