Research

Funding: DFG, 90.000 EUR

Project Details:
VIPER-Immunity against CNS infections caused by the Rift Valley fever virus (RVFV)

Funding: MWK, 439.545 EUR

Project Details:
Flex-Fund project in the COVID-19 research network Lower Saxony:
Mechanisms of short- and long-term effects of SARS-CoV-2 infection on the integrity of respiratory tract epithelia

Results:

https://www.umg.eu/forschung/corona/cofoni/

Funding: MWK über Universität Göttingen, 439.500 EUR

Project Details:
Das Projekt befasst sich mit der Auswirkung einer SARS-CoV-2-Infektion auf die Integrität der Epithelien im Respirationstrakt, mit besonderem Fokus auf die Spätfolgen der Infektion und die Regenerationsfähigkeit. Hierzu wird ein Langzeitversuch im Hamstermodell durchgeführt, in dessen Rahmen Daten für zwei Kernarbeitspakete generiert werden. Im ersten Arbeitspaket werden Auswirkungen auf das ziliierte Epithel in den luftleitenden Wegen untersucht, während das zweite Arbeitspaket sich mit der Schädigung und Regeneration des Alveolarepithels und der daraus resultierenden Folgen für die Lungenfunktion, den Sauerstoffaustausch und die Belastungstoleranz beschäftigt. Zur Auswertung kommt ein breites Spektrum von Analysemethoden zum Einsatz, inklusive funktioneller, pathologischer, virologischer und molekularbiologischer Methoden. Der holistische Ansatz wird unser Verständnis der Pathogenese der Spätfolgen einer COVID-19-Erkrankung maßgeblich erweitern und stellt eine wichtige Voraussetzung für die Entwicklung von Therapieansätzen dar.

Cooperation Partners:

Universität Göttingen

Funding: MWK über Universität Göttingen, 266.300 EUR

Project Details:
Das Mikrobiom der Lunge erfüllt, obwohl signifikant kleiner als das des Darms, eine bedeutende Funktion bei der Regulation der lokalen Immunantwort. Aktuelle Studien zeigten außerdem das SARS-CoV-2 Infektionen bei Betroffenen zu einer Veränderung in der Zusammensetzung des Lungenmikrobioms führen. Im Rahmen des Projektes soll untersucht werden, ob eine durch eine gezielte Manipulation des Lungenmikrobioms ausgelöste Verschiebung der Typ-1-Interferon-Reaktivität in der Lunge die systemische Anfälligkeit für eine SARS-CoV-2-Infektion beeinflusst. Während in der ersten Phase eine genauere Untersuchung der Rolle des Lungenmikrobioms bei der Regulation der homöostatischen Immunantwort erfolgt, wird in der zweiten Phase des Projektes darauf aufbauend die Rolle der Lungenmikrobiota bei der Regulierung der lokalen und systemischen Immunantwort im Rahmen einer SARS-CoV-2-Infektion untersucht. Wenn die in diesen Experimenten gewonnen Daten darauf hindeuten, dass Veränderungen im Lungenmikrobiom einen Einfluss auf den Verlauf der Infektion haben, soll in einem letzten Experiment der Einsatz von Probiotika als pharmakologische Behandlung von SARS-CoV-2-Infektion erprobt werden.

Cooperation Partners:

Universität Göttingen

Project Details:
A vocal repertoire contains a species-specific list of vocalizations, which are produced by the animals. These lists build the methodological and theoretical basis for a number of research questions of different disciplines. Nevertheless, there is no consensus how to establish a vocal repertoire or how to define call types. In the majority of studies, call types were established by visual classification, using spectrograms, which was supported by statistical analysis based on the measured acoustic features of a vocalization. In recent publications, more objective mathematically approaches such as supervised or unsupervised clustering algorithm were established. However, also these algorithm often require a pre-screening of the observer either because a number of expected clusters has to be determined or by the fact that the clustering result has to be proofed for their biological plausibility. Both methods can lead to an overestimation of call types especially in species with very variable vocalizations or graded call types. Thus, an acoustic variation alone is not sufficient to reflect a behavioural relevance. This also requires a context-specificity and the ability of the brain to perceive and process the acoustic variation. In this project, we aim to establish the vocal repertoires by combining the mathematical classification of the vocalizations with the behavioural contexts in which the calls were produced as well as the physical hearing abilities (e.g., hearing range, time- and frequency resolution) of the given species. We use this approach for two small-bodied mammalian species: the Mongolian gerbil, an important animal model for human hearing, and the Etruscan shrew, suggested to be a promising model for hearing in basal mammals due to its small eardrum, basal ossicles, and simple and thin cortex.

Results:

Langehennig-Peristenidou A, Felmy F, Scheumann M (2024). Graded calls of the smallest terrestrial mammal, the Etruscan shrew, living in a closed habitat. iScience, 27(12), 111297. DOI:10.1016/j.isci.2024.111297

 

Silberstein Y, Büntge J, Felmy F, Scheumann M (2024). Context or arousal? Function of drumming in Mongolian gerbils (Meriones unguiculatus). Frontiers in Zoology, 21(1), 22. DOI:10.1186/s12983-024-00542-2

 

Silberstein Y, Felmy F, Scheumann M (2023). Encoding of arousal and physical characteristics in audible and ultrasonic vocalizations of Mongolian gerbil pups testing common rules for mammals. Animals (Basel), 13(16), 2553. DOI:10.3390/ani13162553

Cooperation Partners:

Prof. Dr. A. Kral, VIANNA, Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde

Dr. Wiebke Konerding, VIANNA, Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde

Project Details:
Cooperation strengthens cohesion between animals and is thus a decisive factor for social systems. The present project aims to investigate how individualised relationships - reflected in different types, and amounts, of socio-positive interactions between dyads - shape the social system in a bat model, Carollia perspicillata. A first study will disclose the effects of the interacting individuals, and sex, on cooperative behaviours among bats roosting in stable groups. A second study serves to pinpoint the effect of familiarity on cooperation, using allogrooming and food begging/sharing as paradigms in a series of behavioural experiments. Differences in type, frequency, and duration of interactions, and in the concomitant vocal communication, are expected for experiments with unfamiliar individuals versus those with bats from a given roosting group. The results will contribute to a deeper understanding of how cooperation between individuals may have driven the evolution of bat sociality.

Cooperation Partners:

Prof. Dr. Gerald Kerth,, Zoology and Nature conservation, Zoologisches Institut und Museum, Universität Greifswald

Project Details:
Neurons in the dorsal nucleus of the lateral lemniscus (DNLL) are relevant for binaural processing especially during reverberations. Their basic biophysical and synaptic properties have been documented, but are not understood on the cellular and molecular level. It remains so far unclear what voltage gated ion channels (VGIC) underly their functional specifications and how synaptic inputs are modulated. One specific question that will be answered his how different VGIC (potassium and sodium channels) interact to allow these neurons to generate high firing frequencies at high temporal precision. This biophysical phenotype indicates that these features are differently solved compared to other auditory brainstem neurons with similar tasks. Thus, this project aims to understand the moleculare organisaiton of the postsynaptic integration and spike generation mechanism. Since, the GABAergic DNLL neurons are reziprocally connected substantial GABA is liberated onto each neuron. GABA not only leads to fast inhibitory singalling but also is well-documented to generally be an important neuromodulator in the auditory brainstem. Therefore, the action of GABA mediated neuromodulation will be investigated by characterizing its effect on synaptic inputs and VGIC.

Results:

Javadova A, Felmy F.: GABAB receptor-mediated modulation in the developing dorsal nucleus of the lateral lemniscus. European Journal of Neuroscience (2024) Jan 5. doi: 10.1111/ejn.16246.

Funding: DFG, 350.510 EUR

Project Details:
In mammals, brain and neuron size enlarges with increasing head size. Inevitably, an increase in neuron size results in an increased membrane capacitance. To achieve size-independent synaptic integration and, thus, the function, neuronal properties like input resistance, dendritic morphology, synaptic conductance as well as the number and location of ion channels and synapses must scale proportionally. A prerequisite to investigate the cellular mechanisms of such a scaling is an evolutionary conserved neuronal population that fulfills the same circuit function independent of head and brain size. The neurons of the medial nucleus of the trapezoid body (MNTB) fulfill these criteria and are involved in binaural processing and spectro-temporal integration in the ascending auditory pathway. Quantification of the biophysical and morphological cellular parameters of MNTB neurons and their synaptic input size as well as channel and synapse location in differently sized mammalian species, i.e. Etruscan shrew, gerbil and rat, allows us to grasp the consequences of brain size-dependent neuron scaling. Our electrophysiological and immunofluorescence findings will culminate in a computational model to understand the functional significances of individual neuronal elements. Moreover, we can utilize this comparative approach to investigate the functional role of MNTB dendrites, which remains largely unknown. Specifically, by quantitatively determining the influence of dendritic synaptic inputs on synaptic latency and the success of action potential generation, we can capture their potential role in the generation of high frequency outputs.

Project Details:
Etruscan shrews need to constantly hunt to meet their energy requirements; because of their small body size, their relative energy consumption is very large. To efficiently hunt in close range, these animals rely especially on tactile sensory cues. However, for long-range detection of prey these animals likely use their well-developed hearing. Due to their small body and head size, these animals are expected to hear in frqeuncy range above 5 kHz and therefore are an ideal model system to investigate high frequency hearing and adaptations to miniaturization of mammalian neuronal circuits. We attempt to describe their auditory brainstem strucutes by applying structural and functional markers. After the initial anatomical characterization we will use electrophysiological techniques to comparatively study the properties of adutiory brainstem neurons. Thereby we will focus on biophysical and synaptic size adaptations within conserved neuronal circuits.

Funding: Deutsche Forschungsgesellschaft (DFG), 110.700 EUR

Project Details:
Tetraspanins are evolutionary conserved integral membrane proteins of 200-350 amino acid lengths. Through their large extracellular loop they mediate protein - protein and protein - lipid interactions in cellular membranes thereby shaping membrane microdomains called ?tetraspanin webs?. In humans and mice 33 tetraspanins are described and mosquito species express at least 15 tetraspanin orthologs. In mammalian cells, tetraspanins are host co-factors for several viruses including papillomaviruses, influenza virus, hepatitis C virus, HIV-1 and coronaviruses (Gerold et al., 2015; Bruening et al. 2018; Banse et al., 2018; Alberione et al. 2020; Palor et al., 2020). For hepatitis C virus, colleagues and we showed that the tetraspanin CD81 is a host range determining factor (Vogt et al. 2013; Scull et al., 2015; von Schaewen et al., 2016).
The proposed project aims at characterizing in detail, which of the 33 human tetraspanins in addition to CD81 are host factors for alphaviruses and whether tetraspanins from reservoir species, dead end host species and transmitting mosquito vectors serve as host factors of alphaviruses. Thereby the work will contribute to the understanding of the molecular composition and function of alphavirus replication complexes and determine the role of tetraspanins in species range, transmission and consequently emergence of alphaviruses.