Australian team discovers how one orderly protein protects against cancer

Illustration of three DNA helices
Australian researchers used advanced data-processing tools to visualize the role of the Pax5 protein in DNA. (Darwin Laganzon)

Oncology researchers have long believed the protein Pax5 is merely a “transcription factor,” meaning it helps cells transcribe vital genetic information. But scientists in Australia believe they’ve uncovered evidence that Pax5 actually plays a much bigger role in the body: It organizes DNA in the immune system’s B cells. When that function breaks down, cells can deteriorate, leading to cancer and other diseases, they believe.

Scientists from the Eliza Hall Institute of Medical Research in Melbourne discovered that Pax5 travels across the genome, organizing and storing DNA for B cells in an orderly way that ensures cells will receive the genetic instructions they need to maintain health. This helps the immune system guard against diseases like leukemia, they determined. They published the research in the journal Nature Immunology.

The team made the discovery by studying differences in DNA organization when Pax5 was present and when it was removed from B cells. They used data analysis tools to visualize Pax5’s role in DNA structure, according to a video provided by the institute.

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Pax5 is known to be faulty in many leukemias, but cancer isn’t the only risk associated with a breakdown in the protein’s functioning, said co-author Timothy Johanson, Ph.D., a researcher at the Walter and Eliza Hall Institute, in a statement.

“For instance, immune B cells must access the right information to produce potentially life-saving antibodies that are critical for vaccine and immune responses,” Johanson said. “Think of how a meticulously ordered suitcase increases your chance of finding a specific item of clothing at a moment's notice, and, how a jumbled case could work against you finding what you need. In the case of our bodies, the difference between order and disorder can be a matter of life and death.”

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Despite major advances in treating B-cell cancers—most notably the FDA approvals of personalized CAR-T cell therapies—oncology researchers are still looking for ways to address blood cancers by attacking them from different angles. Some emerging ideas are attracting investor interest, too. In April, for example, Germany-based MorphoSys pulled off a $208 million IPO, the proceeds of which will be used to develop an antibody that’s designed to bind to the CD19 antigen on the surface of B cells and improve the cell signaling that’s vital to their survival.

The Australian team cites advances in data analysis as critical for gaining insights into the functioning of key cancer-related proteins like Pax5. “With the help of powerful computers, we were able to perform millions of complex calculations in a matter of minutes,” said one team member in the video. The researchers say that such tools will help them uncover more factors that determine the difference between healthy and unhealthy DNA.

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