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North Carolina State University's new research shows that genes can identify and respond to light signals. It also filters out certain signals completely. This study demonstrates how one mechanism can trigger multiple behaviors from the same gene and has potential applications for the biotechnology industry.
Albert Keung, assistant professor of chemical-biomolecular engineering at NC State and corresponding author of the paper on the topic, stated that "the fundamental idea is that you can encode data in the dynamics of the signal that a gene receives." "A signal does not have to be present or absent. It is the way it is presented that matters."
Researchers modified yeast cells to produce fluorescent proteins in response to blue light.
This is how it works. The gene's activity is controlled by a region called the promoter. A specific protein binds with the promoter region in modified yeast cells. The protein becomes responsive to another protein when researchers shine a blue light on it. The gene becomes active when the second protein binds with the first protein. This is easy to spot, as activated genes produce proteins that glow in dark.
These yeast cells were then exposed to 119 different light patterns by the researchers. The light patterns varied in intensity, duration, and frequency. Researchers then calculated the amount of fluorescent proteins that cells made in response to each pattern.
It's common to talk about genes being switched on or off. However, it's more like a dimming switch than a light switch. Genes can be activated in a few ways, many times, and anywhere in between. A given light pattern that produced a lot fluorescent protein means that the gene was very active. If the light pattern produced only a small amount of fluorescent protein, it means that the pattern did not trigger any activity.
Jessica Lee, a recent NC State Ph.D. grad and first author of the paper, said that "different light patterns can produce very differing outcomes in terms of gene activation." The big surprise for us was the inextricable correlation between the input and the output. We expected that the stronger the signal would indicate that the gene was more active. This wasn't always the case. Even though both patterns expose the gene to the same amount, one light pattern could make the gene more active than the other.
Researchers discovered that gene activity can be affected by all three variables of light: intensity of the light, frequency and duration of each pulse. However, they found that the researchers could control the frequency of light pulses to have the best control.
Leandra Caywood is a co-author and Ph.D student at NC State.
Caywood explains, "For instance, we discovered that when you combine rapid pulses with light, you get more gene activation than you would expect based on the amount of light applied." The model showed that the proteins don't have the time to separate or come back together fast enough to respond to each pulse. The proteins don't have enough time to separate from one another between pulses so they spend more time connected, meaning that the gene is spending less time activated. These dynamics are very helpful in understanding how to control gene activity with these signals.
Keung states that "our finding is relevant to cells that responds to light such as those found within leaves." It also shows that genes can be responsive to signal patterns which could be transmitted by other mechanisms than light.
This is what it might look like in real life. A chemical signal may be received by a cell. It can be present or absent. The cell can create a pattern signal to target genes in response to the chemical's presence. This is done by controlling how fast the protein bound to the promoter area enters and exits cells. You can think of the control of the protein's presence or absence as sending a message from the cell into the gene. The cell can adjust the message it sends the gene depending on many variables, such as the presence or absence of chemicals.
Keung states, "This means that the same protein can be used to send different messages to the exact same gene." "So the cell could use one protein to make a different response to different chemicals."
The researchers also discovered that genes can filter out certain signals in a separate experiment. This is both simple and complex. Researchers could determine that when a second protein was attached to the promoter of the gene, certain frequencies of light pulses didn't trigger the production fluorescent proteins. Researchers know that the second protein is responsible for ensuring that a gene responds to only a certain set of signals, but they don't know how it does that.
Researchers also discovered that they could alter the signal strength of a gene by manipulating the type and number of proteins attached to its promoter region.
You could attach proteins to your promoter region to reduce the number of activation signals. You could also attach proteins to your promoter region that activate different levels of the gene.
Lee states that "one additional contribution to this work is that it has been determined we can communicate approximately 1.71 bits worth information through the promoter area of a gene without any protein attachments." In practical terms, this means that the gene can distinguish between three signals without error, even if there is no complex network of attachments. This baseline was established by previous work at 1.55 bits. This study expands our understanding of the possibilities. This is a solid foundation upon which to build.
According to the researchers, this research will enable future studies that improve our understanding of gene expression dynamics and cell behavior.
The researchers believe that there will be practical applications in the near future for their work in the biotech and pharmaceutical sectors.
Lee explains that biomanufacturing is about managing both the growth and production of specific proteins. "Our work can help manufacturers fine-tune both of these variables."
The paper "Mapping Dynamic Transfer Functions in Eukaryotic Gene Regulation" will be published in Cell Systems on August 31.
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Further information: Cell Systems, Mapping the Dynamic Trans Functions of Eukaryotic Gen Regulation (2021). Information from the Journal: Cell Systems Mapping Dynamic Transfer Functions for Eukaryotic Gene Regulation (2021).
