A multidisciplinary team of researchers from Lerner Research Institute and Fred Hutchinson Cancer Research Center have been awarded a three-year, $1 million grant from the W.M. Keck Foundation, one of the nation’s largest philanthropic organizations, to study if and how certain bacteria directly alter the human genome, and perhaps even lead to cancer.
“The goal is to look for evidence of specific bacterial-associated changes in the human cancer genome,” said Angela Ting, PhD, associate staff in the Genomic Medicine Institute and co-lead on the project.
Dr. Ting has teamed up with two collaborators from Fred Hutch: Christopher D. Johnston, PhD, a synthetic microbiologist who studies epigenetics of the human microbiome, and Susan Bullman, PhD, a cancer microbiome expert. Together, they will test whether bacterial systems that have evolved to defend against viral infections may also influence how genes are expressed (turned on or off) in human cells, and if these changes may promote cancer.
A new way bacteria could cause cancer?
While mutations that change the letters of DNA code can have big effects on gene expression and function, cells can also control whether genes are turned on or off without altering their DNA sequence. Molecular modifications to DNA that affect how cells read the genetic material, broadly termed epigenetics, can also regulate gene expression.
The researchers are focusing on bacterial enzymes from the microbiome (the community of microbes living in and on the human body), which normally defend the bacteria against viruses by recognizing the presence or absence of methyl groups on DNA. In human cells, addition of a methyl group to DNA (DNA methylation), a form of epigenetic modification, operates as a signaling tool that cells utilize to turn off genes.
“DNA methylation is one of the key global epigenetic changes that we see throughout cancer,” explained Dr. Ting. “There have been countless examples of how abnormal methylation can very effectively turn off tumor-suppressor genes, which then promotes cancer development and cancer growth.” Currently, however, it’s largely unclear how these methylation changes begin.
“There’s a lot of speculation, but not a lot of concrete studies that pinpoint how methylation-related changes occur,” added Dr. Ting. “It’s one of the biggest questions in the field of medicine, and one our specific project hopes to address.”
Bacterial systems may meddle with cell epigenetics
The researchers propose that these cancer-causing methylation changes may arise from bacterial interference. They suspect that certain bacteria can change the epigenetics of our cells and shut down genes that usually prevent tumor formation—without a single DNA letter out of place.
The team will investigate if bacteria can modify our cells’ epigenetics using colorectal cancer as a model. The first step will be to develop the necessary tools and methodologies needed to explore this new field.
If their hypothesis pans out, the findings could be paradigm-shifting in all three researchers’ areas of study. “When we got the funding, I stepped into the lab and said, ‘We finally have the money to turn science fiction into science reality!’” said Dr. Ting.
The award will be split between the labs of Drs. Ting, Johnston and Bullman. Dr. Ting’s lab will receive $335,050.
Story adapted from Fred Hutch News.
About the W. M. Keck Foundation
The W. M. Keck Foundation was established in 1954 in Los Angeles by William Myron Keck, founder of The Superior Oil Company. One of the nation’s largest philanthropic organizations, the W. M. Keck Foundation supports outstanding science, engineering and medical research. The Foundation also supports undergraduate education and maintains a program within Southern California to support arts and culture, education, health and community service projects.