09-Dec-2021 - Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH

A light in the dark tissue

Switchable proteins for biomedical imaging

Biomedical imaging is the window through which we can look into organisms. It allows us to see cells, their behavior and localization that would otherwise be hidden. Tracking very few cells over time without damaging them is a key challenge in health research. For this purpose, Helmholtz Munich researchers engineer natural tools: switchable proteins. Andre C. Stiel talks about their potential for biomedical imaging, his latest study and the challenges of the future.

How do proteins help in biomedical imaging?

Andre: Proteins are molecules made out of amino acids. In our bodies and in all life forms, proteins have many functions – for example they are the machinery that allows the cells to generate energy or receive information. In imaging, we can utilize proteins that generate signals, for example light, to observe what is happening within a live organism. Proteins have the advantage that they are genetically encoded, they can become a component of the cell or the organism – in contrast to, for example, a dye that needs to be added from the outside. In imaging we can use this for something we call labeling. Labels open up exciting possibilities for tracking cells in different states over a long period of time and without having to interfere or damage the living tissue. This allows us, for example, to study a disease or treatment in a relatively natural way and thus to understand diseases better.

What’s the secret of the switchable proteins that you engineer?

Andre: Switchable label proteins can change their state, in our case the signal that we read out, upon illumination with different colors of light. The molecular mechanism acts like a tiny switch that changes the state of the protein from on to off and with that the signal it generates. In nature, those proteins are often responsible for light dependent responses – for example of plants orienting towards the light.

You use switchable proteins in a method called optoacoustic imaging – what is that?

Andre: Optoacoustic imaging – where world-leading research is done at Helmholtz Munich by Vasilis Ntziachristos – is an imaging method that relies on reading out ultrasound signal generated by light. Optoacoustic imaging already has the power to deliver a combination of higher penetration depth, a higher resolution and larger fields of view than other imaging technologies. However, for many research questions optoacoustics needs tools like genetically encoded reporters and sensors. Photoswitchable label proteins can help here. In our research, the light switchable signal enables us to visualize small numbers of cells against a strong background of other signals by making the label blink. You can imagine it as a lighthouse in a stormy dark night at sea. The ability to visualize few cells in a live organism is important because many biological phenomena, especially in the immune system, rely on a small number of cells. Our aim is to one day track single labeled cells in a living organism and visualize their function – to improve our knowledge, for example, about the immune system or about tumor development.

What’s your next challenge?

Andre: We talked about visualizing cells. However, cells themselves host even smaller components of life: small molecules and ions. Often such molecules fulfill very dedicated purposes like communication, or serving as nutrient sources or building blocks for other cellular components, hence they need to be tightly regulated for the cell to function properly. Understanding this regulation is essential to understand life and diseases. In order to visualize small molecules or ions, we don’t use labels but sensors. Sensors can be envisioned like labels that are only visible if the molecule of interest is present – thus, this allows us to visualize the molecules within a cell. In our latest study, we applied our photoswitching concept to sensors. We showed that photoswitching sensors work for optoacoustic as well as for super resolution. Indeed, the application of switchable proteins is not limited to optoacoustics but they are also important tools in super resolution fluorescence microscopy. We developed a concept and a first prototype – with potential for further optimization. Together with Dierk Niessing from Helmholtz Munich we learned the details of the molecular mechanism and together with a group from KTH in Sweden (Ilaria Testa) we made the first super-resolution images using this concept. The sensors will eventually allow us to also visualize small molecule or ion distributions at nanometer resolution. For optoacoustics our goal is to use them to follow small molecules in a whole live animal – that’s the challenge for the next five years.

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH

Recommend news PDF version / Print Add news to watchlist

Share on

Facts, background information, dossiers

  • imaging
  • proteins
  • optoacoustics

More about Helmholtz Zentrum München

  • News

    How tiny changes help T cells survive

    The chemical modification of nucleic acids, known as methylation, exists not only on DNA but also on RNA. So far, it is still unclear whether this methylation is important for certain cell types and what effects it has on the interaction of cells in the body. The most abundant modification ... more

    The oat genome unlocks the unique health benefits of oats

    Researchers have succeeded in sequencing and characterizing the entire genome of oat. Compared to other cereals and humans, the oat genome architecture is very complex. Scientists from Helmholtz Munich, Lund University and the ScanOats network finally elucidated at the genetic level why oat ... more

    A Speed Limit Could Be a Breakthrough for Stem Cell Therapy

    Replacing sick or damaged cells with healthy cells: this is a major goal of regenerative medicine. One of the most promising approaches is cellular reprogramming, whereby one cell type in our body converts to another cell type. Research carried out at Helmholtz Munich and Ludwig-Maximilians ... more

  • q&more articles

    Using deep learning to better understand blood disorders

    For a long time, doctors have been diagnosing disorders of the body’s hematopoietic system using a light microscope. The analysis of individual blood cells is largely performed manually. Now, artificial intelligence can lend them a digital hand. more

  • Authors

    Dr. Carsten Marr

    Carsten Marr, born in 1977, received his diploma in general physics from the Technische Universität München in 2002. He wrote his diploma thesis at the Max-Planck-Institute for Quantum Optics, Garching, Germany, and in 2003 visited the Quantum Information and Quantum Optics Theory Group at ... more

    Dr. Christian Matek

    Christian Matek, born in 1986, received undergraduate degrees in both Physics and Medicine in Munich. He then moved to the UK and finished his DPhil in Theoretical Physics at Oxford University in 2014. Since 2017, his main research interest has been applying artificial intelligence and mach ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by: