The rhythm of signals shapes how cells respond
The same number of light pulses can trigger different responses in cells depending on how regularly they are delivered. A new study from the University of Gothenburg explores how cells interpret signals and regulate their activity.
Optogenetics allows scientists to control genetically modified cells using light. The technique is receiving attention in connection with this year’s Nobel Prize in Physiology or Medicine. In the study, published in the journal iScience, researchers from the University of Gothenburg and collaborating institutions used optogenetics to investigate how cells respond to different patterns of signaling over time.
Erik Smedler is a researcher at Sahlgrenska Academy, University of Gothenburg, where he leads research in molecular psychiatry. He is also the study’s corresponding author:
“We study how cells respond to signals arriving at different rates, much like tuning a radio to different frequencies. Communication between nerve cells is essential for brain function, and our research in psychiatry explores how disruptions in that communication may contribute to mental illness. This study helps us better understand the underlying mechanisms,” says Erik Smedler.
This is basic research into how cells process information and regulate biological processes. Such knowledge could eventually contribute to a better understanding of various diseases.
Timing mattered
The researchers used cultured human cancer cells that had been genetically modified to express melanopsin, a light-sensitive protein normally found in the retina.
Short pulses of blue light activated melanopsin, triggering a series of reactions that included the release of calcium inside the cells. Calcium acts as a messenger within cells and can influence which genes are activated.
Regular light pulses triggered stronger activation of two inflammation-related genes, TNF and IL8, than irregular pulses. This difference emerged even though the cells received the same number of light pulses over one hour.
“We are now also investigating the role of calcium oscillations in glioblastoma, an aggressive form of brain tumour. Previous research has shown that these rhythmic calcium signals can contribute to tumour growth” says Erik Smedler.
Other signaling pathways may be involved
Previous research has shown that cells respond to the frequency of signals. In the new study, the researchers examined how different timing patterns are associated with changes across a broader network of genes and proteins.
They identified changes in the activity of genes associated with MYC, a protein that regulates cell growth. Computational analyses also suggested possible links to pathways involved in cell division and the response to DNA damage.
The study was conducted in cultured cancer cells. Because light stimulation activated several interconnected signaling pathways, the researchers could not isolate the contribution of calcium signal rhythms themselves. Whether the findings extend to other cell types, including nerve cells, remains to be investigated.