optogenetics – Lightsources.org

Filming a vitamin B12 photoreceptor in action

2026/02/132026/02/19

Using X-ray free-electron lasers and synchrotron light at facilities in Switzerland, Japan, France and the UK, a worldwide collaboration of scientists have discovered how a vitamin B12-based photoreceptor works. Understanding how photoreceptors function aids future technological applications, such as optogenetics, that involve controlling cellular processes with light. The findings are published in Nature.

Vitamin B12 is an organometallic cofactor found in many enzymes that control essential processes in various organisms, including humans. It came as a surprise a decade ago that vitamin B12 derivatives had been repurposed for light sensing by a large family of previously unknown photoreceptors in bacteria that fulfil various functions.

The prototypical B12 photoreceptor CarH, for example, regulates the expression of genes involved in protecting bacteria against excess sunlight. It achieves this by binding to DNA in the dark, acting as a molecular doorstop. Upon illumination, its tetrameric architecture breaks apart, enabling transcription by unbinding from DNA.

The way in which this and other B12 photoreceptors function at a molecular level has remained a mystery ever since. However, an international consortium led by scientists at the Institut de Biologie Structurale in Grenoble, France has now combined experimental techniques using X-ray free-electron lasers at the Paul Scherrer Institute PSI in Switzerland (SwissFEL) and Japan (SACLA), as well as the synchrotrons in France (ESRF) and the UK (Diamond Light Source), with quantum-chemical calculations to uncover the inner workings of CarH.

Read more on the PSI website

Image: John Beale is responsible for macromolecular crystallography at the Cristallina experimental station of SwissFEL

Credit: © Paul Scherrer Institute PSI / Markus Fische

ESRF X-rays capture vitamin B12 sensing light

2026/02/102026/02/12

Scientists led by the Institut de Biologie Structurale have combined advanced X-ray methods to unveil how a photoreceptor regulates carotenoid production in bacteria, including experiments at the ESRF. The results are out in Nature.

CarH is a photoreceptor which senses light through a vitamin B12 derivative and regulates carotenoid expression through direct interaction with genes. Bacteria use this remarkable machinery to regulate gene expression and produce carotenoid to protect themselves from photo-damage upon sun exposure. What scientists had never seen before was how tiny photoinduced changes at the vitamin B12 level, propagate into large-scale structural changes triggering a biological response. Now, an international collaboration has managed to film this process in unprecedented detail, with key experiments carried out at the ESRF and at XFELs.

CarH’s role has been clear since around 2015. In the dark, the protein binds to DNA and blocks the production of carotenoids. When light is present, CarH releases the DNA, allowing the cell to produce carotenoids that help defend against light-induced damage.

Previous crystal structures revealed the start and end points of this process. But the crucial missing piece was the journey in between — from the short-lived structural changes that occur immediately after light hits the vitamin B12 molecule to the large-scale conformational changes involving the whole protein structure and its interaction with DNA.

Read more on the ESRF website

Image credit: CEA and Maria Davila Miliani

Research on how light-harvesting bacteria toggle off and on

2019/07/232019/07/31

The results could have long-range implications for artificial photosynthesis and optogenetics—the use of light to selectively activate biological processes.

Cyanobacteria are water-dwelling microbes capable of absorbing sunlight and converting it into chemical energy through photosynthesis. Long ago, ancient versions of these bacteria were incorporated into plant cells, where they eventually evolved into chloroplasts, the organelles responsible for carrying out photosynthesis in green plants. Today, in seeking to develop artificial photosynthesis to harness the sun’s abundant energy, scientists look to cyanobacteria to better understand the nuts and bolts of how natural photosynthesis works.

Cyanobacterial “off switch”

One topic of interest is how cyanobacteria respond to too much light. If a sunlight-harvesting system becomes overloaded with absorbed solar energy, it most likely will suffer some form of damage. Nature has solved the problem in cyanobacteria through a protective mechanism—an energy-quenching “off switch” in which excess solar energy is safely dissipated as heat.

Illustration: X-ray footprinting provides time-resolved information about where key conformational changes occur. On the left is the overall OCP structure. The two structures on the right highlight local areas with increasing protein packing over time (blue shading) and areas with decreasing protein packing over time (red shading). The changes in accessibility are initiated by the movement of the carotenoid molecule (magenta chain).

Biological light sensor filmed in action

2018/06/142018/06/27

Film shows one of the fastest processes in biology

Using X-ray laser technology, a team led by researchers of the Paul Scherrer Institute PSI has recorded one of the fastest processes in biology. In doing so, they produced a molecular movie that reveals how the light sensor retinal is activated in a protein molecule. Such reactions occur in numerous organisms that use the information or energy content of light – they enable certain bacteria to produce energy through photosynthesis, initiate the process of vision in humans and animals, and regulate adaptations to the circadian rhythm. The movie shows for the first time how a protein efficiently controls the reaction of the embedded light sensor. The images, now published in the journal Science, were captured at the free-electron X-ray laser LCLS at Stanford University in California. Further investigations are planned at SwissFEL, the new free-electron X-ray laser at PSI. Besides the scientists from Switzerland, researchers from Japan, the USA, Germany, Israel, and Sweden took part in this study.

Image: Jörg Standfuss at the injector with which protein crystals for the experiments at the Californian X-ray laser LCLS were tested. In the near future, this technology will also be available at PSI’s X-ray laser SwissFEL, for scientists from all over the world.
Credit: Paul Scherrer Institute/Mahir DzaAmbegovic