All posts by : Karin Janz

Our research group aims at improving pain recognition and treatment in animals. As animals cannot communicate verbally their feelings, it is of particular importance to rely on objective tools that allow measuring pain and its modulation in an objective way.

With the financial support of the UniBern Forschungsstiftung we were able to acquire a Dolosys Paintracker (Fig. 1), that allows a non-invasive, continuous determination of the «nociceptive withdrawal reflex» threshold (the pain threshold) in animals of different species. Through surface electrodes, electrical stimuli are applied to a peripheral nerve (Fig. 2) and the evoked muscular response is quantified by electromyography (Fig. 3 and 4). Based on predefined criteria, the software automatically detects the nociceptive threshold and tracks it over time. The automated continuous threshold tracking, compared to the classical methodology applied in past trials, opens new possibilities in several domain of pharmacological and clinical pain research.

At present, with the use of the Dolosys, we aim at developing a Conditioned Pain Modulation (CPM) paradigm that allows quantifying the extent of endogenous pain modulation in healthy horses. Later, the developed CPM tool will be applied to horses affected by chronic pain to establish whether impaired endogenous pain control substantially contributes to the observed clinical pain phenotype, as observed for several chronic pain conditions in humans. This might strongly influence our approach to therapy, increasing the chances of successful clinical outcomes and thus overall contributing to improved animal welfare.

Prof. Dr. Claudia Spadavecchia

Anaesthesiology and Pain Therapy Section
Vetsuisse Faculty

One research topic of the Division of Veterinary Pharmacology & Toxicology at the Vetsuisse Faculty is to explore and understand possible risks of non-ionizing radiation, namely radiofrequency electromagnetic fields (RF-EMF) exposure in the brain. We investigate effects of RF-EMF during different stages of brain development or its effect in the or development of neurodegenerative diseases (e.g., Parkinson’s disease).

Human induced pluripotent stem cell (iPSc)-derived neurons and iPSc-derived brain organoids are used as models. These types of culture require the use of an incubator to minimize humidity, temperature and pH variations during all iPSc expansion periods, induction of neuronal differentiation, and the first week of development of midbrain organoids (Figure 1).

The PHCbi CO2 incubator with four inner doors purchased with the funds provided from the Berne University Research Foundation allowed stable conditions during the culturing even though the incubator was opened various times per day due to the need to medium change etc (Figure 2).

Two projects were successfully completed:
1. Generation and characterization of iPSC-derived dopaminergic neurons to study effects of 5G radiofrequency electromagnetic fields on neuronal development
2. The role of RF-EMF (5G) on neuronal development and neuronal health using brain organoids

The obtained data showed that RF-EMF did not significantly change the investigated markers essential for neural development as well as the maturity and the dopaminergic phenotype. A non-significant trend toward changes in the ERK activation was found, indicating an effect on differentiation if it is not transient.

Preliminary results from 5G RF-EMF exposure with cerebral and midbrain organoid indicated no alteration of neuronal maturity and the dopaminergic phenotype, anda significant decrease in synaptophysin protein levels in cerebral organoids after RF-EMF exposure at day 30, indicating a reduced synaptic activity (Figures 3 and 4). Furthermore, a decrease in neuronal progenitor cells expressed in ventricle-like zones of cerebral organoids, whereas an increase of these cells was found in midbrain organoids.

Further research will include investigations at different times of midbrain development, different specific absorption rates (SAR), and exposure times during neuronal development and disease models of neurodegeneration.

Angélique Ducray, PhD

Senior Scientist
Vetsuisse Faculty

Organs-on-Chip sind fortschrittliche in-vitro Modelle, die die physikalischen und biochemischen Merkmale der zellulären Mikroumgebung nachbilden. Sie bestehen aus mikrofabrizierten Strukturen, die der Grössenordnung von Zellaggregaten ähneln, um die Gewebephysiologie auf kontrollierte Weise zu untersuchen. Dynamische Einflüsse wie Strömung, chemische Gradienten und einwirkende Kräfte können genauestens angepasst werden, um eine organspezifische Umgebung zu schaffen, die den jeweiligen Zellphänotyp aufrechterhält oder zur Zelldifferenzierung anregt. Dies ermöglicht eine funktionelle Gewebesimulation komplexer biologischer Prozesse.

Das ARTORG Organs-on-Chip Technologies Labor ist eine vor 13 Jahren gegründete Forschungsgruppe. Das Labor kombiniert Ingenieurwissenschaften, Mikrofluidik und Zellbiologie und verfügt über modernste Ausrüstung für Chipdesign, verschiedenste Analysen und mikroskopische Bildgebung. Die Organs-on-Chip Facility (OOCF) wurde geschaffen, um Forschende bei der Entwicklung, Herstellung und Prüfung von Chips zu unterstützen, und umfasst ein Mikrofabrikationslabor und ein Zellkulturlabor mit einem speziell ausgebildetem Team. Die OOCF erfreut sich zunehmender Beliebtheit, mit mehr als 40 Nutzenden pro Jahr.

Die bei der UniBern Forschungsstiftung eingeworbenen Mittel wurden für die Anschaffung eines Sauerstoffplasmareaktors sowie einer Laminar-Flow-Werkbank zur Unterbringung des Reaktors verwendet. Der Sauerstoffplasmareaktor ist eines der am häufigsten verwendeten Instrumente im OOCF für die Entwicklung und Produktion von Organs-on-Chips. Das neue System ermöglicht es, höhere Plasmaintensitäten zu erreichen und das Plasma genauer zu steuern.

Als Beispiel für Organ-on-Chips zeigen die beigefügten Bilder ein mikrovaskuläres System aus menschlichen Fibroblasten und Gefässzellen, die sich dank des mikrofluidischen Chips selbst organisieren können. Dieser Mikrovaskulatur-on-Chip wurde mit Hilfe des Sauerstoffplasmareaktors hergestellt. Ein auf diese Weise hergestelltes mikrovaskuläres System erfüllt die spezifischen Gewebefunktionen genauso wie im menschlichen Körper. Auf diese Weise können für die Medizin relevante Untersuchungen einfacher und sicherer durchgeführt werden.

Prof. Dr. Olivier Guenat

Head Organs-On-Chip Technologies

ARTORG Center for Biomedical Engineering Research

Our research group aims to understand climate change (mainly warming and drought) effects on terrestrial biodiversity using microorganisms, invertebrates, and plants from grasslands. Our study approach involves experiments carried out both in the laboratory and in the field. One of our major research frameworks is to incorporate how various life forms (microorganisms, invertebrates, and plants) respond during and after climate extremes (e.g., heat waves). To do so, we measure population dynamics, life history and functional traits of our study organisms.

With the help of the UniBern Forschungsstiftung, we were able to acquire a state-of-the-art widefield microscope (Nikon Ti2 Eclipse) equipped with an automated stage, fluorescence camera, and artificial intelligence (AI) capabilities. Nikon Ti2 Eclipse has become our go-to microscope for high-resolution images to investigate microbial and plant traits in our experiments. Moreover, using AI techniques, we are able to acquire high-throughput data on the fungal colonization (e.g., arbuscular mycorrhizal fungi) of plant roots. Finally, we are using this microscope to understand fungal-bacterial interactions using high-resolution fluorescence images. All these workflows strengthen our research to understand how microscopic organisms respond to climate change.

Prof. Dr. Madhav P. Thakur

Institute of Ecology and Evolution
Division Terrestrial Ecology

terr.iee.unibe.ch

Images by Nicolo Tartini (a), Jingjing Shi (b) and Jan Philip Tscheulin (c)