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Researchers at the University of Jyväskylä are in the process of harnessing the precise and deep-penetrating ability of light to regulate a small cell factory. In the future, a tool placed inside a cyanobacterium will be able to mass-produce proteins for research, or bioplastics and biofuels that only cyanobacteria can produce.

Heikki Takala, an Academy Research Fellow, must peek inside plants, algae, and cyanobacteria to find the subject of his research. Hidden in the depths of the cells is phytochrome, a photoreceptor that enables the cell to respond to red light.

“It can be considered the eye of the cell,” Takala says.

Crystallised phytochrome seen through the lens of a microscope.

Phytochrome is a protein that for example directs the plant towards light, guides the production of coloured pigments produced by bacteria, or stimulates plant seed germination.

The activity of phytochromes also makes the wheat stalks in the field grow evenly, making sure that they do not grow on top of each other.

“The plants adapt to the light conditions of the environment, and such a growth habit ensures there is enough light for all the plants,” Takala says. “They are thus able to function economically.”

According to Heikki Takala, the light-controllability, precision, and ecological benefits make phytochrome proteins excellent research tools.

The construction of the optogenetic tool is progressing fast, as Takala and Researcher Amit Srivastava received funding for the project from the European Commission’s Marie Skłodowska-Curie Actions (MSCA) programme.

Cyanobacteria can produce bioplastic and biofuel

The new optogenetic tool currently being prepared consists of a light-sensing phytochrome component and signalling mechanisms that enable the activation of the desired gene.

The piece of DNA encoding the tool is inserted into the cyanobacteria. When suitable wavelengths of red light are applied to the bacteria , their protein production begins. The underlying biochemical events behind this process are as following:

“The phytochrome component of the tool senses two wavelengths of light, red and far-red light, changing its enzymatic activity. This change activates intracellular signalling cascade, which leads to the activation of the desired gene and protein production,” Takala says.

Takala has recently published a research article about the pREDusk tool in ACS Synthetic Biology in collaboration with Professor Andreas Möglich from the University of Bayreuth.

Based on the pREDusk tool, Takala and Srivastava are now working on the pCDusk tool for cyanobacteria.  Red-light controlled cell factories like that are not yet available on the market or in research laboratories.

What type of protein would you like to produce with the new tool, and for what type of use?

“Using the tool we will develop, we plan to eventually produce bioplastics and biofuel, these are materials that only cyanobacteria can produce efficiently.”

Takala hopes that a small-scale production with a protein factory will be running in the laboratory at the University of Jyväskylä in a few years.

“First, the protein components of the tool must be made to function inside the cyanobacterium,” Takala explains. “We can then replace the gene in the tool to produce desired end products.”

Are you interested in getting involved in more industrial activities?

“I don’t rule that out either, but I don’t think it will happen in the very near future,” Takala says.

Optogenetics is ideal for precise work – it all started with nerve cells

The understanding of mechanisms underlying phytochrome function has gradually increased over time. Methods such as structural biology, biochemistry, and spectroscopy have been used for decades to study what happens in phytochromes when they react to light.

Researcher Amit Srivastava, University of Jyväskylä

The study of photoreceptors is also linked to the field of optogenetics. Optogenetics is generally associated with neuroscience but has now also expanded to other fields.

“The first optogenetic applications were in the field of neurosciences, where researchers were able to control neuronal ion channels  with light,” Takala says.

The light control of phytochromes enables precise tools, enabling activation of even single cells.

These characteristics are also useful in the cell factory, which is currently under development.

“It is easy to control an object with light. The light-sensing part of the phytochrome is either on or off, and no chemicals are needed to regulate the reaction,” Takala says. “The red light also travels deep into the tissue or solution. It is  precise, allowing the activation of even individual bacterial cells.”

Heikki Takala has been studying phytochromes since 2012. He started as an Academic Research Fellow at the University of Jyväskylä in 2020.

The University of Jyväskylä’s high-tech equipment for bioimaging

The use of optogenetic proteins is increasing in many areas of research in Finland. However, new optogenetic tools are still being developed in relatively few Finnish research laboratories.

Heikki Takala has been studying phytochromes since 2012. He started as an Academic Research Fellow at the University of Jyväskylä in 2020.

In phytochrome research, Takala gets to use his skills in structural biology, biochemistry, and cell biology. He was initially drawn to the subject because he was fascinated by the ability of proteins to sense light and the idea of applying this to new purposes.

To determine the structure and function of the phytochromes, Takala and his group utilize high-precision spectroscopic imaging technology, the Laser Laboratory (Laserlab-NSC), and bioimaging equipment in the laboratories of the Department of Biological and Environmental Science of the University of Jyväskylä and the Nanoscience Center.

Why is optogenetics an emerging field?

“For example, many applications in the field of biotechnology or medicine would greatly benefit if the chemicals and other invasive methods were replaced by light,” Takala says. “Light is easy to control, and it reaches places other methods cannot. Optogenetics would enable new therapy forms in which the object is exposed to light directly through the patient’s skin. I believe optogenetics has significant untapped potential.”