New molecular pathway could reveal how cells stick together

Troy 11 January 2007Researchers at Rensselaer Polytechnic Institute have found a new pathway by which cells change their adhesive properties. With a $1,4 million grant from the National Institutes of Health, they plan to fill in the details behind how cells decide to stick to a surface, which could lead to a better understanding of the importance of this pathway to the physiology and development of organisms.

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Cells must interact with each other to produce system responses, like the remodelling of a tissue during development or for orchestration of an integrated immune response. One way they do this is by physically attaching to one another and to surfaces. Andrea Page-McCaw, assistant professor of biology at Rensselaer and principal investigator for the project, has focused on matrix metalloproteinases (MMPs) - proteins that play a role in development and immunity.

"MMPs have gotten a lot of attention primarily because of their regulation in a lot of disease states, most notably cancer and other inflammatory conditions", Andrea Page-McCaw stated. Yet the normal function of these proteins is not well understood.

The job of MMPs is to cleave other proteins that reside in the space in between cells. Andrea Page-McCaw has previously identified a specific protein, called ninjurin, that gets cut by MMP. Now she is working out the interplay between MMPs and ninjurin, with the goal of characterizing this previously unknown pathway by which cells signal to each other.

Ninjurin is anchored to the surface of cells, but after being cut by MMP, a ninjurin segment travels to adjacent cells and signals them to alter their adhesive state. Andrea Page-McCaw published these findings earlier this year and was recently awarded an individual investigator research grant to extend her work from cells in a Petri dish to an organism. The grant, from the National Institute of General Medical Sciences, is for $1,4 million over five years.

"We're trying to figure out how it works in whole flies", Andrea Page-McCaw stated. "When you take a cell out of the organism it behaves a little bit differently. So while you can work out cell mechanisms in cell culture, then you want to go back and demonstrate their relevance to the animal."

To study the role of ninjurin in development and immunity, Andrea Page-McCaw uses a strategy to exclude the protein from the animal. By developing a mutant fly lacking the gene that codes for the protein, she can examine what goes wrong without the protein and then infer the normal function of that protein.

She has previously done similar work knocking out MMP in flies. "One of the defects in MMP mutants is in their ability to control cell adhesion", she stated. Many tissues undergo remodelling as the flies grow and develop, but at least one, the breathing tubes, do not develop properly in the mutant flies. Andrea Page-McCaw calls it a "cellular adhesion defect that causes problems for the animal at the tissue level."

Now she plans to find how ninjurin affects breathing tube development, as well as the role it plays in immunity. "The immune system is all about immune cells circulating around and being able to attach to tissues that need their attention", she stated.

A new signaling pathway holds promise of new therapeutic targets. "We're talking about an entirely new signaling pathway that hasn't been identified previously", Andrea Page-McCaw stated. But it's too soon to know how her findings will be used in terms of human health.

"There are lots of examples of times where the ability of cells to communicate goes awry in disease and ninjurin could be playing a role in any of those", she stated. "The goals of my research are contributions of new ideas and mechanisms that can then be realized by the broader biomedical community."

At Rensselaer, faculty and students in diverse academic and research disciplines are collaborating at the intersection of the life sciences, the physical sciences, and engineering to encourage discovery and innovation. Rensselaer's four biotechnology research constellations - biocatalysis and metabolic engineering, functional tissue engineering and regenerative medicine, biocomputation and bioinformatics, and integrative systems biology - engage a multi-disciplinary mix of faculty and students focused on the application of engineering and physical and information sciences to the life sciences. Ranked among the world's most advanced research facilities, the Center for Biotechnology and Interdisciplinary Studies at Rensselaer provides a state-of-the-art platform for collaborative research and world-class programmes and symposia.

Rensselaer Polytechnic Institute, founded in 1824, is the United States' oldest technological university. The university offers bachelor's, master's, and doctoral degrees in engineering, the sciences, information technology, architecture, management, and the humanities and social sciences. Institute programmes serve undergraduates, graduate students, and working professionals around the world. Rensselaer faculty are known for pre-eminence in research conducted in a wide range of fields, with particular emphasis in biotechnology, nanotechnology, information technology, and the media arts and technology. The Institute is well known for its success in the transfer of technology from the laboratory to the marketplace so that new discoveries and inventions benefit human life, protect the environment, and strengthen economic development.


Leslie Versweyveld

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