Basic Research to Shed Light on Cancer, Birth Defects
Researcher is elucidating the intricacies of chromosome sorting during cell division.
Posted September 1, 2009, 1:00 AM EST
Photo by Melissa Maki
Cells are the fundamental building blocks of life. Each human begins as a single cell. After cell division and development, humans end up with an estimated 100 trillion cells.
The process of cell division, with its careful replication of chromosomes and the DNA that they carry, is incredibly complex. Daniel Foltz, assistant professor of biochemistry and molecular genetics, is elucidating the intricacies of chromosome sorting during cell division.
Foltz received a $50,000 Fund for Excellence in Science and Technology (FEST) Distinguished Young Investigator Grant earlier this year for an in-depth study of the centromere—a locus of control that appears on each chromosome and that helps to regulate cell division and chromosome segregation.
The centromere provides a sort of “check point” that ensures that genetic material is segregated properly when cells divide, says Foltz. In the case of humans, each daughter cell should receive 23 pairs of chromosomes. More or less chromosomes, or the improper segmentation of chromosomes, can result in disease or birth defects.
As a postdoctoral researcher with Don Cleveland’s lab at the University of California, San Diego, Foltz made some seminal contributions to the understanding of the centromere’s identity and operation.
Foltz is continuing this vein of research with his FEST project. He is conducting more traditional biochemical experiments in his own lab and is also partnering with chemistry professor Don Hunt’s lab to take a biochemical mass spectrometry approach to this problem. The goal is to gain a hierarchal understanding of how the centromere’s protein complex is assembled and how exactly the 16 proteins within the complex interact with one another.
Foltz’s plans are novel because previous studies using similar techniques have been conducted on only in vitro assembled complexes. “This hasn’t been done before for protein complexes that are derived from a cell line or an in vivo source,” says Foltz. “We believe this approach will be able to define the individual protein interactions within the endogenous multi-protein complex.”
Foltz’s FEST research has significant implications for the understanding of cancer and birth defects. “We know that it’s a very important event in early development, and missegregation may be a disease causing event in later life,” Foltz explains.
One of the most common types of birth defect—Down’s syndrome—results from having too many copies of chromosome 21. Aneuploidy—or an incorrect number of chromosomes—has also been observed in the majority of cancers.
“It’s not clear whether aneuploidy is a cause of cancer or whether it’s a merely a downstream event—that cells, as they become more cancerous, become less able to segregate their chromosomes,” says Foltz. “What is probably true is that aneuploidy contributes to the difficulty in treating cancer.”
Foltz’s FEST research will not only contribute to the overall understanding of cancer and birth defect development, it may also uncover novel targets for cancer therapies.