Transmitter biobrick: biological modules that send information to the cell

A group of CONICET scientists discovered the operating mechanism of sensory proteins that are located in the cellular outer membrane and allows the cell to communicate with its surroundings.

The study was conducted by the group of the Reverse Bioengineering Laboratory of the faculty of Biochemical and Pharmaceutical Sciences (UNR). It was led by CONICET independent researcher Larisa Cybulski and published in the Journal of Molecular Biology.

“The research focused on the membrane region of sensory proteins. This region was previously thought to be inert and found that its function is crucial,” Cybulsky says.

Synthetic biology and thermogenetics

Synthetic biology is in charge of building nanomachines o biomachines that can perform a specific task following the orders or control of the molecular engineer. “Within synthetic biology there are several branches, we work with the one dedicated to construction of biomachines that arise from the design and knowledge of nature,” Cybulski explains.

At first, the team identified thermosensor modules that work in a protein detecting changes in temperatures. “Our study was based on introducing those modules that are called biobricks –a name that refers to modules or biological bricks- in an inert protein, which did not use to work and made it recover its activity,” the researcher states.

Cybulski explains that one of the correlates of this finding may be linked to Thermogenetics, which tries to use temperatures as a trigger for certain biological processes, that is to say, when the temperature changes, a reaction is triggered.

“This mechanism can be applied in neurobiology, for example in laboratory experimentation in the study of neuronal circuits the temperature of a region of the brain could be modified. Therefore, it can alter the expression of genes of interest in that set of neurons. For this reason, these design proteins -the biobricks- can be used because they will respond to the changes of temperature,” Cybulski indicates.

The protein that is being studied is a protein-kinase that is located in the membranes and functions as a receptor. The receptors are the most intelligent proteins of the cells, while many other proteins work as pawns, the receivers become aware of the situation and perceive the stimuli and give orders, that is, they make decisions that can, for instance, change strategies or express or stop expressing a certain gene.

The researcher explains that there is great scientific interest in understanding how the receptor are regulated because a special group of these intellingent receptor, which are in the membranes of a cell, when they deregulate, turn off, or are hyperactive, can trigger cancer. When giving a signal of growth, the cell should stop dividing. However, it continues to do so because that signaling is altered.

“Although this protein is bacterial, we can understand that the mechanism of how to activate it all the time or how to repress it, then we can manipulate it and decide when to activate or deactivate it. We understand the mechanism and can force a protein to behave in a way or in the opposite way. This helps us to learn about the sensors in general,” emphasizes Cybulski.

“One of the advantages of Themogenetics is that it uses temperature as an inductor, which is a physical sign, while in other systems chemical introducers are used, which bring about certain disadvantages, such as the degradation of compounds, a gradient of concentration, which is toxic, are problems that would be solved or would not exist when using temperature as physical inducer,” says Juan Cruz Almada, CONICET doctoral fellow.

“Before this study we conducted the characterization of the biobricks. It is still necessary to develop a design with a specific function, but with the rationalization of a protein, we can think about something more applied,” Ana Bortolotti, CONICET assistant researcher, explains.