Tag Archives: University of Geneva (UNIGE)

Limiting the side effects of opioids with a new nanobody?

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As someone who lives in a Canadian province (British Columbia) where a public health emergency was declared in 2016 due to drug overdose deaths, this research from Switzerland interests me greatly.

Here’s the situation, eight years after the declaration, the numbers are still rising, from an April 14, 2024 article by Darryl Greer for Canadian Press on the Canadian Broadcasting Corporation (CBC) news online website,

8 years and 14,000 deaths later, B.C.’s drug emergency rages on

More than 14,000 people have died since emergency declared in 2016, largely due to the potent opioid fentanyl

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There’s some promising work from the University of Geneva, which could lessen opioid side effects, from an October 9, 2024 news item on phys.org, Note: A link has been removed,

Opioid drugs are highly effective at relieving pain but come with severe drawbacks. Their side effects range from dizziness to potentially fatal respiratory depression. Their illegal use contributes to nearly half a million deaths worldwide each year.

Researchers from the University of Geneva (UNIGE) have discovered a molecule, called nanobody NbE, which binds tightly and durably to the cell receptors that usually bind to opioids, thereby blocking the drugs’ activity. Moreover, the scientists were able to create even smaller molecules that retain the same properties, which could prove far more effective than current treatments in mitigating the harmful effects of opioids.

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An October 9, 2024 Université de Genève press release (also on EurekAlert), which originated the news item, provides more information about how a nanobody could help blunt opioid side effects,

Opioids are a large family of pharmaceuticals that include morphine, fentanyl and tramadol. These powerful drugs are mainly used as painkillers, but also trigger a euphoric effect by interacting with nerve cells in the brain. However, they are very addictive and produce dangerous side effects. Diverted from their original use, natural and synthetic opioids have become the deadliest drugs in the United States, and this global health crisis is now threatening Europe.


“We need to urgently develop new molecules to better mitigate the side effects for patients and manage the risks of opioid-related overdoses”, explains Miriam Stoeber, associate professor in the Department of Cell Physiology and Metabolism at UNIGE Faculty of Medicine, who initiated and coordinated the project. “To understand how a molecule works, we need to know how it affects the brain cells. In our study, we used tiny natural proteins derived from llama antibodies, called nanobodies, designed to bind specifically to the target receptor on the cell’s surface.”


The strong binding power of nanobody NbE 

UNIGE researchers have found that NbE, one of the nanobodies under study, has the unique ability to bind so tightly and durably to specific opioid receptors that it prevents opioids from binding to these same receptors, therefore blocking the drug’s activity. “To determine how NbE binds to its target, we used high resolution structural biology methods, thanks to the new Dubochet Centre for Imaging”, describes Andreas Boland, assistant professor in the Department of Molecular and Cellular Biology at UNIGE Faculty of Science, and co-last author of the study. “We identified a unique binding mode where only a small portion of the nanobody is responsible for its correct receptor selectivity. Knowing precisely which part of the nanobody is at stake allows us to imagine new ways to induce the same effects with pharmaceuticals.”

Small molecules, large effects 

While significantly smaller than antibodies, nanobodies remain quite large. They can be costly to produce and may not fully reach the target tissue in the body. In collaboration with the Prof. Steven Ballet team from the University of Brussels, the UNIGE research team synthesised in vitro a set of even smaller molecules mimicking the key part of NbE responsible for the selected binding to opioid receptors. “By durably blocking opioid receptors, our new molecules have the potential to reverse or reduce the deleterious side effects of opioids. In case of overdose, they could provide a better, longer lasting option than naloxone, the treatment currently in use. We will now refine their structure to improve even further their efficiency and facilitate their delivery to the targeted nerve cells in the brain”, concludes Miriam Stoeber.

Here’s an illustration of the nanobody at work,

Caption: NbE (red) binds the specific receptor responsible for opioid action (blue) and blocks off other small molecules (white/yellow/red). Credit: © UNIGE

Here’s a link to and a citation for the paper,

Structural basis of μ-opioid receptor targeting by a nanobody antagonist by Jun Yu, Amit Kumar, Xuefeng Zhang, Charlotte Martin, Kevin Van holsbeeck, Pierre Raia, Antoine Koehl, Toon Laeremans, Jan Steyaert, Aashish Manglik, Steven Ballet, Andreas Boland & Miriam Stoeber. Nature Communications volume 15, Article number: 8687 (2024) DOI: https://doi.org/10.1038/s41467-024-52947-6 Published: 09 October 2024

This paper is open access.

European medieval monks, Japanese scribes, and Middle Eastern chroniclers all contributed to volcanology

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Volcanoes are not often a topic on this blog, which is focused on emerging science and technology. However, stories featuring scientific information from unexpected sources has long been a fascination of mine and this April 5, 2023 news item on ScienceDaily shines a light on an unusual cast of medieval scientific observers spanning the globe,

By observing the night sky, medieval monks unwittingly recorded some of history’s largest volcanic eruptions. An international team of researchers, led by the University of Geneva (UNIGE), drew on readings of 12th and 13th century European and Middle Eastern chronicles, along with ice core and tree ring data, to accurately date some of the biggest volcanic eruptions the world has ever seen. Their results, reported in the journal Nature, uncover new information about one of the most volcanically active periods in Earth’s history, which some think helped to trigger the Little Ice Age, a long interval of cooling that saw the advance of European glaciers.

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llumination from the late 14th or early 15th century, which portrays two individuals observing a lunar eclipse. It features the words «La lune avant est eclipsee», «The moon is eclipsed» in english. © Source gallica.bnf.fr / BnF Courtesy: Université de Genève

An April 5, 2023 Université de Genève (UNIGE) press release (also on EurekAlert), which originated the news item, includes observations from Japanese scribes along with those from medieval European monks and Middle Eastern scholars,

It took the researchers almost five years to examine hundreds of annals and chronicles from across Europe and the Middle East, in search of references to total lunar eclipses and their colouration. Total lunar eclipses occur when the moon passes into the Earth’s shadow. Typically, the moon remains visible as a reddish orb because it is still bathed in sunlight bent round the Earth by its atmosphere. But after a very large volcanic eruption, there can be so much dust in the stratosphere – the middle part of the atmosphere starting roughly where commercial aircraft fly – that the eclipsed moon almost disappears.

Medieval chroniclers recorded and described all kinds of historical events, including the deeds of kings and popes, important battles, and natural disasters and famines. Just as noteworthy were the celestial phenomena that might foretell such calamities. Mindful of the Book of Revelation, a vision of the end times that speaks of a blood-red moon, the monks were especially careful to take note of the moon’s coloration. Of the 64 total lunar eclipses that occurred in Europe between 1100 and 1300, the chroniclers had faithfully documented 51. In five of these cases, they also reported that the moon was exceptionally dark.

The contribution of Japanese scribes 

Asked what made him connect the monks’ records of the brightness and colour of the eclipsed moon with volcanic gloom, the lead author of the work, Sébastien Guillet, senior research associate at the Institute for environmental sciences at the UNIGE,  said: “I was listening to Pink Floyd’s Dark Side of the Moon album when I realised that the darkest lunar eclipses all occurred within a year or so of major volcanic eruptions. Since we know the exact days of the eclipses, it opened the possibility of using the sightings to narrow down when the eruptions must have happened.”

The researchers found that scribes in Japan took equal note of lunar eclipses. One of the best known, Fujiwara no Teika, wrote of an unprecedented dark eclipse observed on 2 December 1229: ‘the old folk had never seen it like this time, with the location of the disk of the Moon not visible, just as if it had disappeared during the eclipse… It was truly something to fear.’ The stratospheric dust from large volcanic eruptions was not only responsible for the vanishing moon. It also cooled summer temperatures by limiting the sunlight reaching the Earth’s surface. This in turn could bring ruin to agricultural crops.

Cross-checking text and data 

“We know from previous work that strong tropical eruptions can induce global cooling on the order of roughly 1°C over a few years,” said Markus Stoffel, full professor at the Institute for environmental sciences at the UNIGE and last author of the study, a specialist in converting measurements of tree rings into climate data, who co-designed the study. “They can also lead to rainfall anomalies with droughts in one place and floods in another.”

Despite these effects, people at the time could not have imagined that the poor harvests or the unusual lunar eclipses had anything to do with volcanoes – the eruptions themselves were all but one undocumented. “We only knew about these eruptions because they left traces in the ice of Antarctica and Greenland,” said co-author Clive Oppenheimer, professor at the Department of Geography at the University of Cambridge. “By putting together the information from ice cores and the descriptions from medieval texts we can now make better estimates of when and where some of the biggest eruptions of this period occurred.”

Climate and society affected 

To make the most of this integration, Sébastien Guillet worked with climate modellers to compute the most likely timing of the eruptions. “Knowing the season when the volcanoes erupted is essential, as it influences the spread of the volcanic dust and the cooling and other climate anomalies associated with these eruptions,” he said.

As well as helping to narrow down the timing and intensity of these events, what makes the findings significant is that the interval from 1100 to 1300 is known from ice core evidence to be one of the most volcanically active periods in history. Of the 15 eruptions considered in the new study, one in the mid-13th century rivals the famous 1815 eruption of Tambora that brought on ‘the year without a summer’ of 1816. The collective effect of the medieval eruptions on Earth’s climate may have led to the Little Ice Age, when winter ice fairs were held on the frozen rivers of Europe. “Improving our knowledge of these otherwise mysterious eruptions, is crucial to understanding whether and how past volcanism affected not only climate but also society during the Middle Ages,” concludes the researcher.

Here’s a link to and a citation for the paper,

Lunar eclipses illuminate timing and climate impact of medieval volcanism by Sébastien Guillet, Christophe Corona, Clive Oppenheimer, Franck Lavigne, Myriam Khodri, Francis Ludlow, Michael Sigl, Matthew Toohey, Paul S. Atkins, Zhen Yang, Tomoko Muranaka, Nobuko Horikawa & Markus Stoffel. Nature volume 616, pages 90–95 (2023) Issue Date: 06 April 2023 DOI: https://doi.org/10.1038/s41586-023-05751-z Published online: 05 April 2023

This paper is open access.

Bidirectional prosthetic-brain communication with light?

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The possibility of not only being able to make a prosthetic that allows a tetraplegic to grab a coffee but to feel that coffee  cup with their ‘hand’ is one step closer to reality according to a Feb. 22, 2017 news item on ScienceDaily,

Since the early seventies, scientists have been developing brain-machine interfaces; the main application being the use of neural prosthesis in paralyzed patients or amputees. A prosthetic limb directly controlled by brain activity can partially recover the lost motor function. This is achieved by decoding neuronal activity recorded with electrodes and translating it into robotic movements. Such systems however have limited precision due to the absence of sensory feedback from the artificial limb. Neuroscientists at the University of Geneva (UNIGE), Switzerland, asked whether it was possible to transmit this missing sensation back to the brain by stimulating neural activity in the cortex. They discovered that not only was it possible to create an artificial sensation of neuroprosthetic movements, but that the underlying learning process occurs very rapidly. These findings, published in the scientific journal Neuron, were obtained by resorting to modern imaging and optical stimulation tools, offering an innovative alternative to the classical electrode approach.

A Feb. 22, 2017 Université de Genève press release on EurekAlert, which originated the news item, provides more detail,

Motor function is at the heart of all behavior and allows us to interact with the world. Therefore, replacing a lost limb with a robotic prosthesis is the subject of much research, yet successful outcomes are rare. Why is that? Until this moment, brain-machine interfaces are operated by relying largely on visual perception: the robotic arm is controlled by looking at it. The direct flow of information between the brain and the machine remains thus unidirectional. However, movement perception is not only based on vision but mostly on proprioception, the sensation of where the limb is located in space. “We have therefore asked whether it was possible to establish a bidirectional communication in a brain-machine interface: to simultaneously read out neural activity, translate it into prosthetic movement and reinject sensory feedback of this movement back in the brain”, explains Daniel Huber, professor in the Department of Basic Neurosciences of the Faculty of Medicine at UNIGE.

Providing artificial sensations of prosthetic movements

In contrast to invasive approaches using electrodes, Daniel Huber’s team specializes in optical techniques for imaging and stimulating brain activity. Using a method called two-photon microscopy, they routinely measure the activity of hundreds of neurons with single cell resolution. “We wanted to test whether mice could learn to control a neural prosthesis by relying uniquely on an artificial sensory feedback signal”, explains Mario Prsa, researcher at UNIGE and the first author of the study. “We imaged neural activity in the motor cortex. When the mouse activated a specific neuron, the one chosen for neuroprosthetic control, we simultaneously applied stimulation proportional to this activity to the sensory cortex using blue light”. Indeed, neurons of the sensory cortex were rendered photosensitive to this light, allowing them to be activated by a series of optical flashes and thus integrate the artificial sensory feedback signal. The mouse was rewarded upon every above-threshold activation, and 20 minutes later, once the association learned, the rodent was able to more frequently generate the correct neuronal activity.

This means that the artificial sensation was not only perceived, but that it was successfully integrated as a feedback of the prosthetic movement. In this manner, the brain-machine interface functions bidirectionally. The Geneva researchers think that the reason why this fabricated sensation is so rapidly assimilated is because it most likely taps into very basic brain functions. Feeling the position of our limbs occurs automatically, without much thought and probably reflects fundamental neural circuit mechanisms. This type of bidirectional interface might allow in the future more precisely displacing robotic arms, feeling touched objects or perceiving the necessary force to grasp them.

At present, the neuroscientists at UNIGE are examining how to produce a more efficient sensory feedback. They are currently capable of doing it for a single movement, but is it also possible to provide multiple feedback channels in parallel? This research sets the groundwork for developing a new generation of more precise, bidirectional neural prostheses.

Towards better understanding the neural mechanisms of neuroprosthetic control

By resorting to modern imaging tools, hundreds of neurons in the surrounding area could also be observed as the mouse learned the neuroprosthetic task. “We know that millions of neural connections exist. However, we discovered that the animal activated only the one neuron chosen for controlling the prosthetic action, and did not recruit any of the neighbouring neurons”, adds Daniel Huber. “This is a very interesting finding since it reveals that the brain can home in on and specifically control the activity of just one single neuron”. Researchers can potentially exploit this knowledge to not only develop more stable and precise decoding techniques, but also gain a better understanding of most basic neural circuit functions. It remains to be discovered what mechanisms are involved in routing signals to the uniquely activated neuron.

Caption: A novel optical brain-machine interface allows bidirectional communication with the brain. While a robotic arm is controlled by neuronal activity recorded with optical imaging (red laser), the position of the arm is fed back to the brain via optical microstimulation (blue laser). Credit: © Daniel Huber, UNIGE

Here’s a link to and a citation for the paper,

Rapid Integration of Artificial Sensory Feedback during Operant Conditioning of Motor Cortex Neurons by Mario Prsa, Gregorio L. Galiñanes, Daniel Huber. Neuron Volume 93, Issue 4, p929–939.e6, 22 February 2017 DOI: http://dx.doi.org/10.1016/j.neuron.2017.01.023 Open access funded by European Research Council

This paper is open access.

Chameleons (male panther chameleons in particular)—colour revelation

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Caption: These are male panther chameleons (Furcifer pardalis) photographed in Madagascar. Credit: © Michel Milinkovitch

Caption: These are male panther chameleons (Furcifer pardalis) photographed in Madagascar.
Credit: © Michel Milinkovitch

Researchers at Switzerland’s University of Geneva/Université de Genève (UNIGE) have revealed the mechanisms (note the plural) by which chameleons change their colour. From a March 10, 2015 news item on phys.org,

Many chameleons have the remarkable ability to exhibit complex and rapid color changes during social interactions. A collaboration of scientists within the Sections of Biology and Physics of the Faculty of Science from the University of Geneva (UNIGE), Switzerland, unveils the mechanisms that regulate this phenomenon.

In a study published in Nature Communications [March 10, 2015], the team led by professors Michel Milinkovitch and Dirk van der Marel demonstrates that the changes take place via the active tuning of a lattice of nanocrystals present in a superficial layer of dermal cells called iridophores. The researchers also reveal the existence of a deeper population of iridophores with larger and less ordered crystals that reflect the infrared light. The organisation of iridophores into two superimposed layers constitutes an evolutionary novelty and it allows the chameleons to rapidly shift between efficient camouflage and spectacular display, while providing passive thermal protection.

Male chameleons are popular for their ability to change colorful adornments depending on their behaviour. If the mechanisms responsible for a transformation towards a darker skin are known, those that regulate the transition from a lively color to another vivid hue remained mysterious. Some species, such as the panther chameleon, are able to carry out such a change within one or two minutes to court a female or face a competing male.

A March 10, 2015 University of Geneva press release on EurekAlert (French language version is here on the university website), which originated the news item, explains the chameleon’s ability as being due to its ability to display structural colour,

Besides brown, red and yellow pigments, chameleons and other reptiles display so-called structural colors. «These colors are generated without pigments, via a physical phenomenon of optical interference. They result from interactions between certain wavelengths and nanoscopic structures, such as tiny crystals present in the skin of the reptiles», says Michel Milinkovitch, professor at the Department of Genetics and Evolution at UNIGE. These nanocrystals are arranged in layers that alternate with cytoplasm, within cells called iridophores. The structure thus formed allows a selective reflection of certain wavelengths, which contributes to the vivid colors of numerous reptiles.

To determine how the transition from one flashy color to another one is carried out in the panther chameleon, the researchers of two laboratories at UNIGE worked hand in hand, combining their expertise in both quantum physics and in evolutionary biology. «We discovered that the animal changes its colors via the active tuning of a lattice of nanocrystals. When the chameleon is calm, the latter are organised into a dense network and reflect the blue wavelengths. In contrast, when excited, it loosens its lattice of nanocrystals, which allows the reflection of other colors, such as yellows or reds», explain the physicist Jérémie Teyssier and the biologist Suzanne Saenko, co-first authors of the article. This constitutes a unique example of an auto-organised intracellular optical system controlled by the chameleon.

The press release goes on to note that the iridophores have another function,

The scientists also demonstrated the existence of a second deeper layer of iridophores. «These cells, which contain larger and less ordered crystals, reflect a substantial proportion of the infrared wavelengths», states Michel Milinkovitch. This forms an excellent protection against the thermal effects of high exposure to sun radiations in low-latitude regions.

The organisation of iridophores in two superimposed layers constitutes an evolutionary novelty: it allows the chameleons to rapidly shift between efficient camouflage and spectacular display, while providing passive thermal protection.

In their future research, the scientists will explore the mechanisms that explain the development of an ordered nanocrystals lattice within iridophores, as well as the molecular and cellular mechanisms that allow chameleons to control the geometry of this lattice.

Here’s a link to and a citation for the paper,

Photonic crystals cause active colour change in chameleons by Jérémie Teyssier, Suzanne V. Saenko, Dirk van der Marel, & Michel C. Milinkovitch. Nature Communications 6, Article number: 6368 doi:10.1038/ncomms7368 Published 10 March 2015

This article is open access.