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subcellular organization

Keith Maggert

Keith Maggert

To learn more about how DNA and inheritance works, Keith Maggert has spent much of his nearly 30 years as a researcher studying what takes place not just within the DNA genome but also the subtle modifications of it. That’s where a stable of enzymes add chemical marks to DNA, turning individual genes on or off without changing their underlying sequence. What’s really intrigued Maggert is these “epigenetic” modifications are maintained through cell division and can even get passed down from parent to child over many generations. Like many researchers, he wants to know how it happens.

Maggert thinks there’s more to the story than scientists have realized. Now an associate professor at the University of Arizona College of Medicine, Tucson, he suspects that a prominent subcellular structure in the nucleus called the nucleolus also exerts powerful epigenetic effects. What’s different about the nucleolus, Maggert proposes, is it doesn’t affect genes one by one, a focal point of current epigenetic research. He thinks under some circumstances its epigenetic effects can activate many previously silenced, or “off” genes at once, sending cells and individuals on a different path toward health or disease.

Maggert has received a 2016 NIH Director’s Transformative Research Award to pursue this potentially new paradigm. If correct, it would transform current thinking in the field and provide an exciting new perspective to track epigenetics and its contributions to a wide range of human diseases, including cancer, cardiovascular disease, and neurodegenerative disorders.


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Bacteria are single-cell organisms that reproduce by dividing in half. Proteins within these cells organize themselves in a number of fascinating ways during this process, including a recently discovered mechanism that makes the mesmerizing pattern of waves, or oscillations, you see in this video. Produced when the protein MinE chases the protein MinD from one end of the cell to the other, such oscillations are thought to center the cell’s division machinery so that its two new “daughter cells” will be the same size.

To study these dynamic patterns in greater detail, Anthony Vecchiarelli purified MinD and MinE proteins from the bacterium Escherichia coli. Vecchiarelli, who at the time was a postdoc in Kiyoshi Mizuuchi’s intramural lab at NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), labeled the proteins with fluorescent markers and placed them on a synthetic membrane, where their movements were then visualized by total internal reflection fluorescence microscopy. The proteins self-organized and generated dynamic spirals of waves: MinD (blue, left); MinE (red, right); and both MinD and MinE (purple, center) [1].


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