Study of rock wallabies could have implications
in identifying human medical conditions

Photo: Peter Morenus

Rachel O’Neill, assistant prof. of molecular & cell biology.

The centromere doesn’t look like much under a microscope—just a tiny knot of a chromosome. But this basic cellular structural element is a source of fascination for UConn’s Rachel J. Waugh O’Neill, who has spent hours trying to unravel its secrets. Part of her research involves separating the double-stranded DNA helix to map dye-marked genes onto chromosomes and examining their multi-colored configurations under a fluorescent microscope.

“The centromere is the site in a chromosome that’s essential for cellular division,” explains O’Neill, assistant professor of molecular and cell biology. “We know how it works functionally, from yeast to humans, but the sequence is very different between closely related species, and we don’t understand why that is.”

O’Neill monitors the work of five graduate students and one undergraduate student in her third floor laboratory at Beach Hall. A Texas native, O’Neill earned her Ph.D. at La Trobe University in Australia and arrived at UConn in 1999.

She is studying centromeres in several animal models, but it is O’Neill’s research on a small kangaroo species known as the rock wallaby that has attracted international attention — and a five-year National Science Foundation grant. Rock wallabies are marsupials, a type of mammal that diverged from the eutherian branch of the mammalian species, which includes humans, around 180 million years ago.

O’Neill’s passion for her work stems from a “Eureka” moment occurring when, as a graduate student working on gene-mapping, she noticed an amplified retrovirus while peering at a rock wallaby chromosome under a microscope. The discovery created a stir in the scientific community.

“I couldn’t believe it,” O’Neill says. “It had long been thought the centromere did not contain functional genes, but we’ve found functional retroviruses exist at the centromere in marsupials.”

Perhaps best known for their insidious role in AIDS, retroviruses exist primarily to replicate themselves. O’Neill explains that retroviruses are parasitic and use a cell’s machinery to make their own proteins. Normally retroviruses lay silent because the genome has mechanisms to silence them, but O’Neill’s research is finding they also have a specific function in a cell.

“What’s remarkable is they’re active in the marsupial genome,” she says.

Photo: Rachel O'Neil

A female rock wallabie with her young. Rock wallabies are marsupials, mammals that diverged from the eutherian branch of the mammalian species, which include humans, more than 180 million years ago.

O’Neill and her students are trying to determine how retroviruses are functioning structurally at the centromere, and they are sequencing large portions of the genome to find out the differences between an active centromere and a silent one.

They are studying centromeres in animals, including deer mice bred in UConn laboratories and rock wallabies living in a colony in Australia. O’Neill says rock wallabies are an especially good research model because they have large chromosomes and can produce new hybrids rapidly.

“We think this type of chromosome change is happening more frequently in hybrids, which are a cross between two different species, and this is why we’ve moved into looking at other species,” O’Neill says. “We think there’s a relationship between hybrids and chromosome rearrangements, and we’re trying to understand why they occur and what instabilities they create. The marsupials we’ve looked at have undergone rapid chromosomal change, and the vast majority involved the centromere.”

She says the research could have important implications for humans: “The types of random rearrangements you can see in humans often are associated with centromeric instability. A lot of times there are fertility defects, such as parents unable to have children, or they produce other medical problems from cancer to immune system deficiencies.”

“I do what I do because I love science,” O’Neill says. “I am here to answer questions and know that with every question we answer, we raise 10 more.”

Her team of student researchers is currently writing papers about topics such as placental defects in mouse hybrids, retroviral activation in mouse hybrids and a
“full characterization” of the retrovirus in marsupials.

O’Neill is eager to share her enthusiasm for her work with her students, who each focus on illuminating a piece of the centromere puzzle.

“I often end up learning from them, which is how it should be,” she says.

— Karen Singer ’73 (CLAS)