Scientists use microchip approach to visualize human breast cancer proteins

A photograph may reveal how something looks, but direct observation can divulge how the objects behave. The difference can mean life or death, especially when it comes to fighting human disease.

To help researchers examine exactly how human diseases work at the molecular level, Virginia Tech Carilion Research Institute scientist Deborah Kelly has developed a new set of tools to peer into the active world of cancer cells at unprecedented resolution.

Kelly and her team published the instructions in Scientific Reports, an open-access journal from the Nature publishing group.

"A single high-resolution snapshot of an isolated protein can only tell us so much, in health or disease," said Kelly, who is also an assistant professor of biological sciences in Virginia Tech's College of Science. "We can learn much more about how a protein works and how its function might be changed in response to a genetic mutation if we can see how it interacts with other molecules."

Kelly and her team developed the new toolkit to examine, in detail, the BRCA1 protein and its associated parts in a near-native environment. The scientists collected the protein and the protein assemblies from the nuclear material of human breast cancer cells.

"This is the first demonstration of our technology, which lets us directly visualize macromolecular regulatory complexes in human patient-derived cancer cells," Kelly said. "We chose initially to study the BRCA1 protein precisely because it accounts for about a quarter of genetic breast and ovarian cancers, and its function is still so poorly understood."

In human cells, BRCA1 is a tumor-suppressing protein that helps repair damaged genetic material when cells grow and divide. BRCA1 helps proofreads the DNA templates and works to correct errors.

Mutations in BRCA1 disrupt normal cellular processes that regulate proper growth and division. The resulting misguided actions in cell growth due to mutated BRCA1 are heavily correlated with breast and ovarian cancers.

"The manner in which BRCA1 works in concert with other protein machinery is ill defined at the molecular level," Kelly said. "And the three-dimensional structures of complexes containing BRCA1 are under-investigated, despite the potential important clinical significance."

Scientists know that the BRCA1 protein can associate with other protein-binding partners to assist with genomic safeguarding.

"It's critical to better understand these associations and how things go wrong in these highly regulated events, which ultimately play a major role in triggering the cancer process," Kelly said.

Kelly and her team developed the microchip-based toolkit to examine the genetic material contained within the breast cancer cells.