In this project, the investigators will engage high school, undergraduate, and graduate students in cutting-edge cell biology research to discover how compartments within cells change shape in response to nutrient availability. Mitochondria are energy-generating compartments present in large numbers in complex cells. Mitochondria have a characteristic shape in different cell types, which is closely correlated to function. The shape of mitochondria is also highly dynamic, and can readily shift to adapt to different energy requirements. To discover shared mechanisms for establishment and maintenance of mitochondrial shape, the researchers will use model organisms from a group of single-celled parasites called the kinetoplastids. Kinetoplastids are unusual in that each cell contains only a single mitochondrion that undergoes dramatic changes in structure and function as the parasites alternate between insect and mammalian hosts. This arrangement greatly facilitates the analysis of changes in mitochondrial structure, and will reveal shared mechanisms by which cells control the number and distribution of their mitochondria. Due to their evolutionary position, kinetoplastids possess a basal set of mitochondrial shape proteins, the investigation of which will provide insight into how these processes work in a wide variety of cell types. To allow for better understanding of these complex structures, engineering students will create mitochondrial models using a 3-D printer. This interdisciplinary effort will illustrate the connections between engineering and biology, and will demonstrate how this technology may be applied for enhanced understanding and communication of fundamental questions in cell biology.
Kinetoplastid parasites such as Crithidia fasciculata and Trypanosoma brucei have long been important models for basic cellular processes. Kinetoplastid mitochondria in particular have unusual features, including the fact that there is only one mitochondrion per cell. This necessitates a thus far unknown mechanism for regulation of mitochondrial biogenesis and division within the cell cycle. In addition, the shape and function of the mitochondrion are dramatically and reversibly altered in different life cycle stages of the parasite. In other organisms, mitochondrial shape is established and maintained by membrane fusion and fission events, collectively called mitochondrial dynamics. While much of the machinery for mitochondrial dynamics has been described in yeast and humans, how these processes are regulated is not well understood, and not all mitochondrial dynamics proteins are conserved. The investigators will use a variety of cellular and molecular biology techniques to identify the mechanisms controlling mitochondrial shape in kinetoplastids, providing important insight into how these processes evolved and their function in other organisms.
