Yeast Cell and Mitochondria
Our lab has been studying yeast mitochondria since 2002. Mitochondria are of particular interest because they are the 'hub' of iron metabolism, since they are involved in iron-sulfur cluster and heme biosynthesis. We have characterized iron distribution in both whole yeast cells (Saccharomyces cerevisiae) and isolated mitochondria. We have studied differences in iron distribution relative to growth medium (rich or minimal medium, growth conditions (fermenting or respiring conditions; aerobic or anaerobic growth), as well as the effect of mutations in certain proteins associated with yeast iron metabolism (such as Atm1, Yah1 and Aft1). We are currently investigating 1) the effect of iron concentration in the growth medium and 2) the effect of Mtm1 deletion on iron distribution within the yeast cell and mitochondria 3) the redox states of heme centers in yeast mitochondria.
Yeast vacuoles are relevant to iron metabolism because they are known to function as the major iron storage organelles in yeast. We have recently embarked on a project involving isolation of yeast vacuoles and characterization of the form of iron stored. We are also interested in studying the functions of different vacuolar membrane proteins involved in iron import or export into and from the vacuoles.
Human Cell and Mitochondria
Our lab is also involved in studying iron distribution in human cells and mitochondria. We are investigating iron uptake and utilization by a human leukemic cell line (Jurkat cells). Studying human cells is of interest because iron metabolism in yeast and human cells are similar in some ways but differ in other ways, such as the modes of iron uptake, storage and regulation.
Mice whole organs and isolated mitochondria
We have recently embarked on a project involving isolation of mice organs of interest and mitochondria from these organs to study iron distribution. In mammals, iron homeostasis involves not only signaling within individual cells, but also communication between cells from different organs. Mice provide the perfect model for studying iron metabolism of mammals at the level of the whole organism.
Isolation of Low-Molecular Weight Iron Complexes
In addition to iron-sulfur clusters and hemes, iron is also present as low-molecular weight complexes, which are hypothesized to act as the 'labile iron pool' from which proteins and organelles derive the iron they need. This 'labile iron pool' is of particular importance because if present in excess, it may cause cellular damage through formation of reactive oxygen species (ROS). One of the projects in our lab involves the chromatographic isolation and characterization of these LMW complexes.
Computational Cell Biology
We are trying to build a biochemical model of actomyosin ring dynamics in animal cells. We are attempting to mathematically model the mechanism of ring assembly and disassembly. We are currently using the fission yeast Schizosaccharomyces pombe as a physical model. Once we understand the ring mechanism in the S. pombe, we can apply its general properties to other animal cases.