Research

Funding: Epilepsy Foundation, 200.000 EUR

Project Details:
Tuberous sclerosis complex (TSC) is a genetic disease, which leads to elevated PI3K/mTOR signaling and causes development of tumors in different organs as well as epileptic seizures, developmental delay, and autism. Therapy is limited to often ineffective anti-seizure drugs (ASDs), surgery, and rapalogs (everolimus), the first generation mTOR inhibitors. Recently, everolimus has been approved for treatment of ASD-refractory partial-onset seizures in patients with TSC. However, this therapy is associated with severe adverse events, including immunosuppression. We have developed novel, ATP-competitive, specific, brain penetrant mTOR and PI3K/mTOR inhibitors, which have a much better safety profile; particularly these compounds lack immunosuppressive activity.

Cooperation Partners:

PIQUR, Basel, Schweiz

Funding: DFG, 333.650 EUR

Project Details:
Die Infektion mit dem Theilerschen murinen Enzephalomyelitisvirus (TMEV) stellt ein anerkanntes Modell zur Erforschung viraler Enzephalitiden und degenerativer Prozesse bedingt durch neurotrope Viren dar. Antigen-präsentierende Zellen (APZ) werden hierbei maßgeblich für Neuronenschäden im Hippocampus von infizierten C57BL/6-Mäusen verantwortlich gemacht. Aktivierende und inhibierende C-Typ Lektinrezeptoren (CLRs) auf APZ wirken an der Pathogenerkennung mit und tragen daher essentiell zur Immunhomöostase bei verschiedenen Infektionskrankheiten bei. Die Bedeutung von CLRs in der Neuropathogenese der TME ist bislang allerdings unklar. Basierend auf der Hypothese, dass eine Dysregulation der CLR-Aktivierung für die Immunpathologie im Gehirn und Neurodegeneration verantwortlich ist, soll in dem geplanten Projekt die Bedeutung von CLRs bei der TMEV-Infektion untersucht werden.

Funding: DFG, 352.662 EUR

Project Details:
Binaural coincidence detection relies on the precise excitation-inhibition interaction in neurons of the medial superior olive (MSO). This precision is achieved through alterations during late postnatal development, a period marked by the establishment of prominent structure-function relationships in the auditory system. How excitatory inputs to MSO neurons refine during late postnatal development is unknown. In this proposal, we plan to mechanistically investigate these processes, through quantification of the developmental changes of excitatory currents and the morphology of axonal input patterns. To unravel what drives these changes we will perform these experiments in gerbils raised in omnidirectional white noise, which suppresses relevant sensory spatial cues. Conversely, the impact of sound-evoked activity will be eliminated using cochlear ablations. Applying both forms of sensory manipulation will allow us to distinguish whether sound evoked activity or the experience of spatial cues is crucial for functionally important circuit refinements in the MSO. Thus, our study will provide a quantitative insight into mechanisms that drive the development of synaptic excitation at an ultrafast coincidence detector neuron important for sound source localization.

Results:

Kladisios N, Wicke KD, Pätz-Warncke C, Felmy F.: Species-Specific Adaptation for Ongoing High-Frequency Action Potential Generation in MNTB Neurons. Journal of Neuroscience 2023 Vol 43:2714-2729

Pätz C., Console-Meyer L., Felmy F.: Structural arrangement of auditory brainstem nuclei in the bats Phyllostomus discolor and Carollia perspicillata. Journal of Comp Neurology, 2022, Vol. 530, 2762-2781; IF: 3.028

 

Siveke I, Myoga MH, Grothe B, Felmy F.: Ambient noise exposure induces long-term adaptations in adult brainstem neurons. Scientific Reports 2021 Mar 4; 11:5139.

 

Franzen D.L., Gleiss S.A., Kellner C.J, Kladisios N., Felmy F.: Activity-dependent calcium signaling in neurons of the medial superior olive during late postnatal development. Journal of Neuroscience, 2020, Vol. 40(8):1689-1700

Funding: BfN, 549.313 EUR

Project Details:
The implementation of the Marine Strategy Framework Directive (2008/56/EG, MSFD) aims to achieve a good environmental status (GES) of the European oceans until 2020. The MSFD obliges all European coastal states to effectuate the development and execution of national marine strategies. It sets a tight time schedule for the accomplishment of several obligations, like the results of the status assessments of the German North and Baltic Seas, which have to be reported to the European Commission regularly, the determination of the GES of the German marine areas and the determination of environmental targets. In the context of this range of tasks, the Institute for Terrestrial and Aquatic Wildlife Research shall support the Federal Agency for Nature Conservation (BfN) scientifically, in order to perform the existing reporting duties and actions timely and with professional quality. Approaches to the evaluation of the biodiversity status within the MSFD will be compiled on international, national and regional levels, refined and different approaches will be harmonised.

They will be processed nationally as well as internationally in different committees and working groups (for example in the International Council for the Exploration of the Sea (ICES)) and debated within regional marine protection treaties (Oslo and Paris Commission (OSPAR) and Helsinki Commission (HELCOM)). The cooperation regarding the MSFD and partially the Council Directive on the conservation of natural habitats and of wild fauna and flora will be organised within the framework of BLANO in Germany. Currently, the assessments (for example scientific indicators) are being compiled and modulated in the different working groups. A continuous cooperation is necessary in the various working groups, in order to guarantee a sufficient incorporation of German research results and indicator concepts on international level. This is enabled within the framework of this project.
The ITAW has developed and implemented extensive research proposals and monitoring drafts with a focus on marine mammals for Germany in the past, with the result that long-term data and basics are available for indicator configuration at the ITAW. These shall be included in this process. The existing results provided by the ITAW, scientific analyses and considerations on the indicator configuration shall contribute to the international process, because the indicator development also presents an important tool for future monitoring research projects. Furthermore, it is also necessary from the scientific point of view to reconcile and effectuate the implementation and validation of indicators as well as monitoring efficiency on international level, because marine mammals are such highly mobile species.

Results:

https://doi.org/10.3389/fmars.2021.795953

Project Details:
The base of the project is the identification of a specific need in high-quality research training in marine sciences including the study of a broad variety of marine organisms at the European level. In spite of being evolutionary distant from Humans, marine species can bring fundamental knowledge that can be transferable to understand molecular and cellular processes governing several aspects of human biology. In addition, marine organisms constitute an important source of biomolecules with putative industrial and therapeutic applications making the development of marine resource a key area in the field of blue economy and blue growth. Considering the above-described contect, the present strategic partnership will develop a thourough research training focused on the use of marine organisms in several life science disciplines such as neurobiology, cell morphogenesis/cell biology, tissue regeneration, evolution/life cycle and marine biotechnology.

Cooperation Partners:

Prof. Dr Agnes Boutet (Sorbonne, Frankreich),

Prof. Dr. Stefano Piraino, Neapel

Project Details:
Die Messbarkeit und Aussagekraft der beim Menschen etablierten cardialen Biomarker Galectin-3 und ST2 wird im Rahmen dieses Projekts aus dem Serum von gesunden Hunden und Hunden in verschiedenen Stadien einer Mitralklappenerkrankung gemessen. Hierzu wird bei den untersuchten Hunden Blut abgenommen und es erfolgt eine echokardiografische Untersuchung, in deren Rahmen das Vorliegen einer Mitralklappenerkrankung abgeklärt und eine Stadieneinteilung nach der modifizierten CHIEF-Klassifikation durchgeführt werden. Zusätzlich werden die beim Hund etablierten cardialen Biomarker NTproBNP und CTnI gemessen und es wird nach einer Korrelation der verschiedenen Biomarker gesucht. Diese Untersuchungen sollen zu einer verbesserten Diagnostik und Prognosestellung der Mitralklappenerkrankung des Hundes führen.

Funding: BmBF, 331.351 EUR

Project Details:
Entwicklung und Evaluation eines auf Dengue-Virus zugeschnittenen Systems für Immunogenitätsstudien

Funding: Bundesministerium für Bildung und Forschung, 500.218 EUR

Project Details:
Directive 2010/63/EU obliges a more consistent implementation of the 3Rs principle in the use of animals for scientific purposes, with the consequence of increased research activities in this field. The University of Veterinary Medicine Hannover and the Philipps University Marburg want to support these 3R research activities in a joint effort through a pilot project to establish an open access training platform for 3R methods and to make 3R methods more transparent and visible.

Results:

3R SMART

Directive 2010/63/EU requires a more consistent implementation of the 3Rs principle in the use of animals for scientific purposes, resulting in increased research activities in this field. The Hanover University of Veterinary Medicine Foundation and the Philipps University of Marburg wanted to support these 3R research activities and make them more transparent and visible through a pilot project to set up an open access training platform for 3R methods.

The aim of the project was to set up an open access training platform for 3R methods that would (A) make visible the high level of scientific, but also industry-driven commitment to the development of alternative methods to animal testing, in order to (B) offer not only information that relates specifically to individual 3R methods, but also fundamental background information on the 3R concept (e.g. on the ethical classification of the 3R concept). (C) to offer the training content in the form of short, easy-to-understand video contributions and thus usefully supplement the text-based content of established alternative methods databases (e.g. AnimAlt-ZEBET, DB-ALM).The content was closely aligned with the recommendations from the workshop "Teaching Alternative Methods to Animal Experimentation", which was organized by the Center for Alternatives to Animal Testing in Europe (CAAT) and the Transatlantic Think Tank for Toxicology (t4). According to these recommendations, the high degree of diversification of knowledge about 3R methods makes it necessary to teach the essential contents of the 3R concept in a modular way. In the 3R-SMART, this is achieved through modules on 3R background information (basic modules) and on individual 3R methods (advanced modules). To ensure broad acceptance of the 3R-SMART, the EU Center for Alternatives to Animal Testing, the German Center for the Protection of Laboratory Animals (Bf3R) at the BfR, the EU Berlin with the Berlin-Brandenburg research platform BB3R, and BASF were involved in designing the content.

The 3R-SMART has been online since March 2020 and has already been very popular. A total of 1,097 visitors were already registered via the web analytics platform Matomo in 2020, although it is expected that this development can be significantly increased with the optimizations planned in the expansion period.

Cooperation Partners:

Philipps-Universität Marburg, Deutsches Zentrum zum Schutz von Versuchstieren (Bf3R) am BfR, FU Berlin mit der Berlin-Brandenburger Forschungsplattform BB3R, BASF

Funding: QS Fachgesellschaft Geflügel GmbH, 100.000 EUR

Project Details:
Die Ziele des Forschungsprojektes sind
-die Untersuchung des Einflusses der Bebrütungs- und Haltungstemperaturen auf die Translokation von Enterococcus cecorum aus dem Darm
-die Untersuchung des Einflusses des Mikrobioms auf die Entstehung von Enterokokkeninfektionen
Es gibt bisher keine Daten zu möglichen Interaktionen zwischen Haltungstemperatur, Darmintegrität und EC-Infektion bzw. Darmmikrobiom, Lincomycin/Spectinomycin-Behandlung und EC-Infektion. In dieser Studie sollen diese Zusammenhänge erstmals systematisch untersucht werden. Die Ergebnisse sollen helfen, Erkrankungen durch Enterokokken bei Masthähnchen besser zu verstehen und dadurch besser vorbeugen zu können.

Project Details:
Pankreas und Nebenniere sind endokrine Organe die häufig im Fokus der bildgebenden Diagnostik stehen. Im Rahmen einer Studie sollen Abgrenzbarkeit, Attenuation und Volumen dieser Organe beim heranwachsenden Hund ermittelt werden um Normwerte für eine Untersuchung zu etablieren. Weiterhin soll untersucht werden ob rassespezifische Unterschiede in der computertomographischen Darstellung von Nebenniere und Pankreas beim adulten, gesunden Hund vorliegen. Eine Validierung der Daten ist durch eine Beurteilung verblindeter, randomisierter Datensätze durch mehrere Gutachter vorgesehen.