Cellular research yields body of knowledge to fight disease, disorders

November 30, 2012 | UToday, Natural Sciences and Mathematics
By Cynthia Nowak

Think of them as cellular building blocks — which determine whether or not you’ll become blind.

Every cell in your body possesses a centrosome. Every centrosome contains a pair of centrioles, each built from a cylindrical array of 9 microtubules. And extending from each cell are hair-like protrusions called cilia.

Dr. Tomer Avidor-Reiss demonstrated the capabilities of the University’s new confocal microscope by examining the cellular structures that become apparent in a single hair from a fruit fly.

For more than 100 years following their discovery, these universal cellular subunits have been considered a sort of family, each with roles essential to life.

Dr. Tomer Avidor-Reiss, associate professor in the Department of Biological Studies, turns that family picture upside down.

“From my point of view, centrosomes, centrioles and cilia are the same,” he said. “It’s like the stages of life in which you begin as an infant, grow into a child and later into an adult. It’s the same with these cellular structures, which are stages of development.”

Avidor-Reiss, who came to the UT College of Natural Sciences and Mathematics this year from Harvard University, is utilizing a newly renovated research laboratory in Wolfe Hall to study these long-mysterious organelles — cellular components with specialized functions.

“For many years, centrosomes were thought to be critical for cell division, orchestrating how chromosomes move; we know now that’s a mistake,” he noted. “Centrosomes play a part in that, but their vital role is cilia formation.”

Cilia have their own areas of biological primacy. Cells without cilia, or with defective cilia, are linked to disorders that include blindness, kidney disease, male infertility and developmental abnormalities such as microcephaly.

As Avidor-Reiss explained it, “Within the cell, centrosomes are big structures. Cilia are kind of a compartment for rent, which evolution will fill with necessary functions, depending on whatever species is renting. In the fruit flies [Drosophila melanogaster] we work with, cilia provide the capacity to feel and smell. Other organisms use cilia to see or move. Whatever the biological context is, the organism through evolution will modify the cilia to its need.”

Today, Avidor-Reiss’ team is focusing on a group of proteins that seem to affect the centrosome. If the researchers’ hunch is correct, the proteins also may regulate cilia formation. “Once we can discover what these proteins do, we hope to connect that discovery with some aspect of human health,” he said.

Such basic research — also called pure research — is performed in the hope that it may someday be applied to developing a disease treatment or cure.

Cancer is one such disease. In centrosome research, Avidor-Riess explained, scientists have identified a major difference between a normal cell and a cancer cell: too many centrosomes in the cancer cell.

“So people like me notice the difference in the cells, and ask if we can use that information to kill the cancer cell. Most cancer drugs today are helpful but crude; they’re killing the patient as they kill the cancer. The next phase of drugs should be specific to the cancer cells.”

His group’s last published paper centered on their discovery that by regulating a particular protein in the amorphous pericentriolar matrix surrounding the two centrioles, they could create a larger centrosome — a phenomenon that seems to pose few problems for a normal cell. But what about cancer cells, with their abnormal number of centrosomes?

They plan to explore, he said, whether activating those larger centrosomes in cancer cells could drive the cells into a reproductive dead end.

Another project centers on his group’s discovery of a heretofore unknown structure in Drosophila sperm: in fact, an embryo centriole. “We think it is important in fertilization, and it is possible that even human sperm may have this structure. Mutations in it might explain human infertility,” Avidor-Reiss said.

“It could not have been identified before because the necessary tools didn’t exist.”

One of those tools sits in his laboratory now: the confocal microscope purchased by the University, a half-million-dollar piece of technology that advances the department’s capabilities several levels. “It allows us to look into very complex tissue, where you must be able to focus and gather information from one focal plane. That’s what a confocal microscope does best,” he explained. “It’s really a beautiful machine with high sensitivity and resolution. We are able to see two centrioles in a row and the transitions where the connection is made to the cilia.

“We’d always tried to do it at Harvard, but didn’t succeed.”

Despite its nomenclature, the work of Avidor-Reiss and his group may well prove to be anything but basic, as science continues to uncover internal structures of biology that were hidden until this moment.

The UT scientist agreed. “Cilia and centrosomes may well represent a new type of biology, one that goes beyond cell division and simple sensory function. Only recently, the importance of centrosomes and cilia in the nervous system has become evident, and new studies have connected ciliary defects to neuropsychiatric disorders.

“If we have learned anything from the past, it is that future research into centrosomes and cilia is likely to hold many more surprises.”

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