In diseases such as cancer and congestive heart failure, sheets of cells break down. Jessica Maiers is researching a basic process that cells use to stick together to gain insight into the nature of human disease.
Maiers, a Ph.D. student in the Interdisciplinary Graduate Program in Molecular and Cellular Biology, has identified novel molecular mechanisms that can link and seal these connections between cells. She has recently presented her findings at a national cell biology meeting and is preparing them for publication.
“We’ve been trying to describe the process as a zipper,” says Maiers. “First the cells form, then they come together, and seal at the top.”
Maiers works in the lab of UI faculty member Kris DeMali, who says the speed of these molecular events as sheets of cells come together is a big research challenge. Advanced microscope technology helps, but it is difficult to slow the process down to really dissect it. DeMali says Maiers has overcome this hurdle by exploiting the laboratory’s combined expertise in cell biology and biochemistry.
“Unlike some of the more descriptive studies that are out in the field,” DeMali says, “Jess has been able to give us a model with more mechanistic insight, so you know some of the actual players involved.”
Some of the players include protein complexes at the adherens junctions that work as a link between cells, and tight junctions, which are intercellular junctions that can be thought of as a sealant.
“The adherens junctions anchor neighboring cells together and the tight junctions seal up the spaces between the cells,” says DeMali. “The adherens junctions can then be thought of as the nails that hold two boards together and the tight junctions are like the caulking that fills in the empty spaces.
Maiers says most cancer deaths arise from the spreading of a primary tumor from one organ to part of another non-adjacent organ. In order for tumors to invade and spread, cell-to-cell contacts must be disrupted. “When these contacts are disrupted, you’re more susceptible to diseases,” Maiers says.
In the case of blood vessels, Maiers says adherens junctions hold the vessels together, but tight junctions prevent the blood from leaking out and fluid from coming in. “This maintains cell structure, to a point,” says Maiers. “There are many factors, but the tight junctions prevent blood from leaking from the vessels into the rest of your body.”
Maiers has found that the interaction between an adherens junction protein known as alpha catenin and ZO-1, a tight junction protein, are critical for efficient zippering or sealing.
Before Maiers developed her model, DeMali says there were two contradictory models explaining how this might occur. “Jess reconciled those models and came up with a more complete model that explains both of them,” says DeMali. “Through her work, she’s been able to resolve that and fill a real gap in the knowledge.”
Maiers says the breakthrough came while “trying to understand part of the literature that might have been contradictory to what we were doing, but instead we found that a model really connected this idea with other ideas in the field that brought everything together in a really nice way.”
Maiers’ research is supported, in part, by a predoctoral fellowship from the American Heart Association.