Genes operate under the watchful eye of their regulatory elements. But in spite of these efforts, genes can still go haywire.
Studying how these regulatory regions assert or lose their power over oncogenes might show how cancer works at the molecular level. SwitchGear Genomics, a company founded in 2005 by three Stanford University geneticists, has a new tool that allows researchers to peer into what controls the cancer genome. “We developed new approaches and new technology that actually characterizes these, what we’re calling DNA switches … in living cells in a high-throughput way,” says Nathan Trinklein, CEO and co-founder of SwitchGear Genomics. The idea is that after the cancer-regulation regions are characterized, they can be scanned to help develop new anticancer therapies.
The genome, says Trinklein, is not just genes. Non-coding regions, such as regulatory regions, are integral to a properly functioning cell. While part of the ENCODE project, Trinklein and his colleagues developed a technology that eventually helped them build SwitchGear’s new tool, the Oncology Functional Promoter Macroarray. This contains a panel of regulatory regions for known oncogenes that are spliced into vectors containing a luminescent reporter gene. The genes whose regulatory regions are contained on their panel were garnered from previous studies and gene annotations, and are involved in DNA damage, apoptosis, and cell cycle control. “This tool can be used to study, basically to characterize, cancer cells and to say which of these switches are being acted on differently in cancer cells compared to normal cells,” Trinklein says.
The tool can also be used to screen how cancer cells react to different treatments. By exposing cells in this assay to different conditions, whether a potential therapy or damage, a researcher could track how the cells’ gene transcripts change by tracing the output of the tool, as read by a luminometer. “The hope is then that you can use this as a screening tool for understanding how compounds affect cancer cells in more detailed ways,” Trinklein says. That’ll help scientists “understand if different DNA sequences might actually respond differently to certain types of cancer.”
Studying regions of gene regulation reaches beyond oncology. Not only does SwitchGear plan to tackle other conditions such as hypoxia and heart disease, the team plans to ramp up from its current small family sets to having “a genome-wide tool that will allow people to study the genome in a whole way,” says Trinklein.