A light-activated potassium channel for neuronal inhibition. This is the study that won the eighth Aspen Institute Italia Award for collaboration and scientific research between Italy and the United States.
The work is the result of collaboration between the Ion Channel Biophysics laboratory of the University of Milan Department of Biosciences, led by Anna Moroni – where Laura Alberio constructed the new protein BLINK2 – and the Neuromodulation of Cortical and Subcortical Circuits Laboratory, led by Raffaella Tonini of the Istituto Italiano di Tecnologia in Genoa – where Andrea Locarno demonstrated that protein’s functionality on neuronal activity.
This study was published in the internationally renowned journal Nature Methods. Along with the University of Milan and the Istituto Italiano di Tecnologia in Genoa, researchers collaborated with Columbia University, in New York City, and the University of Arizona, in Tucson, to demonstrate the efficacy of a new synthetic protein that, activated by blue light, can alleviate neuropathic pain. In this context, the development of synthetic proteins that respond to light is a goal of paramount importance for treating pathologies linked to the hyperexcitability of neurons, such as chronic neuropathic pain, which has so far proved difficult to treat.
It is in this scenario that the work of Anna Moroni’s laboratory falls. Under the prestigious European Research Council grant (ERC-Advanced grant), the lab builds synthetic ion channel proteins that can be activated remotely by physical stimuli such as light, ultrasound and magnetic fields. Already, in 2015, the lab’s work had led to the development of the protein BLINK1, born of the combination of an ionic channel of viral origin with a light-sensitive protein drawn from plants. These stimuli have the advantage of penetrating deep into tissues and can therefore be used to control cell functions remotely, i.e. non-invasively. Such channels find application in various areas of research – particularly neuroscience – as they allow cell activity to be controlled reversibly and with high temporal resolution.
This is why BLINK2 was tested in the laboratory of Rajesh Khanna (University of Arizona, Tucson) in an animal model of neuropathic pain: the results showed that BLINK2 was able to alleviate pain in a rat exposed to a source of blue light for more than half an hour. The repercussions of this work may lead to possible new neurological therapies.
As Raffaella Tonini put it: “Together with Andrea Locarno, the other primary co-author of the study, we have not only demonstrated that BLINK2 (Cosentino et al., Science, 348 (6235): 707-710) is able to inhibit neuronal activity in the mammalian brain, but that this inhibition persists in the dark for many minutes, differentiating it from other optogenetic tools, which operate on millisecond and second scales.” The applications of this technological innovation can be manifold. “The fact that BLINK2 inhibits neuronal activity for tens of minutes,” comments Anna Moroni, “makes it particularly suitable for controlling persistent neuronal hyperexcitability, as in the case of chronic pain.”
The study was a collaboration between twenty-eight scientists from the following organizations:
University of Milan, Department of Biosciences and Department of Pharmacological and Biomolecular Sciences
- Anna Moroni (corresponding author together with Raffaella Tonini)
- Laura Alberio (Co-first author with Andrea Locarno)
- Monica Beltrame
- Monica Di Luca
- Elena Marcello
- Silvia Moleri
- Silvia Pelucchi
- Alessandro Porro
- Edoardo Romano
- Andrea Saponaro
- Federica Simeoni
Istituto Italiano di Tecnologia, Genoa, Neuromodulation of Cortical and Subcortical Circuits Laboratory, Neuroscience and Brain Technologies Department, and Center for Neuroscience and Cognitive Systems, Rovereto
- Raffaella Tonini (corresponding author together with Anna Moroni)
- Arjen J. Boender
- Andrea Contestabile
- Andrea Locarno (Co-first author with Laura Alberio)
- Massimo Pasqualetti
Columbia University, New York City, Department of Physiology and Cellular Biophysics
- Henry M. Colecraft
- Anna Moroni
University of Arizona, Tucson, Department of Pharmacology
- Rajesh Khanna
- Yingshi Ji
- Shizhen Luo
- Aubin Moutal
University of Florence, Department of Neuroscience, Psychology, and Child Health, Section of Pharmacology and Toxicology
- Silvia Pelucchi
University of Pisa, Department of Biology
- Massimo Pasqualetti
- Noemi Barsotti
National Research Council, Milan, Institute of Biophysics
- Anna Moroni
- Giulia Romani
Institut Curie, PSL Research University, La Sorbonne University, Paris
- Shahad Albadri
- Valérie Bercier
- Filippo Del Bene
Technische Universität, Darmstadt, Department of Biology
- Gerhard Thiel
- Kerri Kukovetz
The Award
The Aspen Institute Italia Award for scientific research and collaboration between Italy and the United States was launched in December 2015 in keeping with the Institute’s commitment to encouraging and developing international leadership and transatlantic relations. Every year, the prize will be awarded to a research project studying applied or theoretical natural sciences, in which scientists and/or organizations from Italy and the US collaborate.
The members of the Award committee are:
- Hon. Professor Giulio Tremonti, Chairman of the Award committee; Chairman, Aspen Institute Italia, Rome
- Professor Cristina M. Alberini, Center for Neural Science, New York University, New York
- Professor Alessandra Buonanno, Director, Max Planck Institute for Gravitational Physics – Albert Einstein Institute, Potsdam
- Professor Domenico Giardini, Chair of Seismology and Geodynamics, ETH, Zurich
- Professor Luciano Maiani, Professor Emeritus of Theoretical Physics, “La Sapienza” University, Rome
- Professor Giovanni Rezza, Prevention Director General, Ministry of Health, Rome
- Mr. Lucio Stanca, Vice Chairman, Aspen Institute Italia,Rome