Overview of research projects

Project Details:
Das Projekt untersucht die Pathogenese der Rifttalfieberenzephalitis im Mausmodell. Rifttalfieber ist eine virale Zoonose, die in seltenen, aber schweren, teils fatalen Fällen zu einer Enzephalitis in Humanpatienten führt. Wichtige Details zu deren Pathogenese, insbesondere der Infektionsweg, die intrazerebrale Virusausbreitung und die Rolle der (intrazerebralen) Immunantwort sind bisher nicht vollständig geklärt. Das Projekt erforscht den Verlauf der Rifttalfieberenzephalitis nach intranasaler Infektion bei verschiedenen immundefizienten Knockoutmäusen im Vergleich mit immunkompetenten Wildtypmäusen, um die genaue Rolle verschiedener Immunzellen in der Pathogenese zu charakterisieren.

Results:

https://pubmed.ncbi.nlm.nih.gov/36293352/ (2022 Oct 18)

Funding: Gesellschaft der Freunde der Tierärztlichen Hochschule Hannover e.V. (GdF), 15.600 EUR

Project Details:
Growing evidence indicates that exercise has the potential to reduce components of Parkinson's disease (PD)-related pathology. PD progression starts early before onset of the cardinal motor signs and subtle motor and non-motor dysfunctions are evident even in the early prodromal stage before clinical disease diagnosis (Berg et al. 2021 Nat Rev Neurol). We therefore examine whether and to which degree exercise affects disease pathology and progression in young mice that overexpress human wildtype alpha-synuclein under the Thy-1 promotor (Thy1-aSyn mice) and replicate PD hallmarks by developing, among others, robust fine motor deficits at two months of age (Chesselet, Richter et al. 2012 Neurotherapeutics). We hypothesize that early intervention by exercise has a disease-modifying effect during prodromal phase in Thy1-aSyn mice and can be applied as a non-pharmacological preventive strategy for early-stage PD (Schäffer et al. 2020 Neurology). Next, we will administer a substance to the animal model, which shows increased levels under exercise and neuroprotective properties in other neurodegenerative diseases.

Cooperation Partners:

Prof Dr. Daniela Berg (Neurologie, Christian-Albrechts Universität Kiel), Prof. Dr. Christiane Wrann (Harvard Medical School)

Funding: F. Hoffmann-La Roche Ltd, 236.600 EUR

Project Details:
exploratory research project

Funding: EU, 1.234.225 EUR

Project Details:
Bewertung von rational konzipierten Influenza-Impfstoffen

Funding: DFG Ra 50/23-1, 2, Houston Zoo, 344.938 EUR

Project Details:
Drivers of speciation are diverse and complex, ranging from large-scale geomorphological processes like the formation of mountains or rivers to small-scale mechanisms like intra-specific ecological plasticity, divergent habitat choice or colonization potential. Due to the lack of appropriate model regions and species, previous studies typically focused on single or dual factor approaches without investigating interactions between drivers. We propose a highly suitable model region in eastern Madagascar to better explore the principal evolutionary processes driving species diversification and their interactions. The proposed study region is traversed by several large rivers that differ greatly in age. The geology and vegetation is rather uniform with similar macro-habitats ranging from tropical lowland to highland rain forest along an elevational east-west gradient. The area harbors an outstanding lemur species richness of which three genera are chosen as models for this project. Thirteen model species belong to two exceptionally speciose genera, Lepilemur and Microcebus, in contrast to the less speciose but ecologically plastic genus of woolly lemurs (Avahi). Rivers and mountains are assumed to have played a crucial role during speciation of lemurs, providing refugia during Pleistocene glaciation events which supposedly facilitated speciation. We propose that river chronology is an additional major co-variate shaping diversification processes, colonization pathways and phylogeographic history of species. We aim to combine geomorphological reconstructions of relative river ages, (micro-)habitat characterizations, ecological niche modeling techniques and RADseq-based phylogeographic reconstructions of colonization routes to investigate the role and interactions of various drivers of speciation including chronology of riverine barriers, vagility, altitudinal tolerance, body size, and ecological plasticity. This interdisciplinary project will thereby illuminate the relative importance of various extrinsic (e.g., geomorphology, habitat) and intrinsic factors (e.g., ecological plasticity, vagility) for the evolutionary diversification of animal populations.

Results:

Tiley, G.P.*; van Elst, T.*; Teixeira, H.; Schüßler, D.; Salmona, J.; Blanco, M.B.; Ralison, J.M.; Randrianambinina, B.; Rasoloarison, R.M.; Stahlke, A.R.; Hohenlohe, P.A.; Chikhi, L.; Louis, E.E.; Radespiel, U.; Yoder, A.D. (2022): Population genomic structure in Goodman?s mouse lemur reveals long-standing separation of Madagascar?s Central Highlands and eastern rainforests. Mol. Ecol., 31, 4901-4918. https://doi.org/10.1111/mec.16632 (*: shared first authors)

 

Schüßler, D.#; Blanco, M.B.#; Salmona, J.; Poelstra, J.; Andriambeloson, J.B.; Miller, A.; Randrianambinina, B.; Rasolofoson, D.W.; Mantilla-Contreras, J.; Chikhi, L.; Louis, E.E. Jr., Yoder, A.D.; Radespiel, U. (2020): Ecology and morphology of mouse lemurs (Microcebus spp.) in a hotspot of microendemism in northeastern Madagascar, with the description of a new species. Am. J. of Primatol., e23180. https://doi.org/10.1002/ajp.23180 (#: joint first authors)

 

Poelstra, J.#; Salmona, J. #; Tiley, G.P. #; Schüßler, D.; Blanco, M.B.; Andriambeloson, J.B.; Manzi, S.; Campbell, C.R.; Bouchez, O.; Etter, P.D.; Iribar, A.; Hohenlohe, P.A.; Hunnicutt, K.E.; Johnson, E.A.; Kappeler P.M.; Larsen, P.A.; Ralison, J.M.; Randrianambinina, B.; Rasoloarison, R.M.; Rasolofoson, D.W.; Stahlke, A.R.; Weisrock, D.; Williams, R.C.; Chikhi, L.; Louis Jr., E.E.; Radespiel, U.* Yoder, A.D.*; (2020): Cryptic patterns of speciation in cryptic primates: microendemic mouse lemurs and the multispecies coalescent. Systematic Biology, syaa053. https://doi.org/10.1093/sysbio/syaa053 (#: joint first authors, *: joint senior authors)

Cooperation Partners:

Prof. Dr. M. Sauerwein, Universität Hildesheim

Dr. Jordi Salmona, Universität Toulouse, Frankreich

Dr. Lounès Chikhi, IGC, Oeiras, Portugal

Pr. Dr. Jonah Ratsimbazafy, Universität Antananarivo, Madagaskar

Pr. Dr. Solofonirina Rasoloharijaona, Universität Mahajanga, Madagaskar

Dr. Romule Rakotondravony, Universität Mahajanga, Madagaskar

Dominik Schüßler, Apl.Prof. Dr. Jasmin Mantilla-Contreras, Universität Hildesheim

Funding: EU Kommission (imi), 337.500 EUR

Project Details:
The objective of WP3 is to combine the broad expertise of consortium partners in drug discovery in order to identify small molecule candidate drugs to fight coronaviruses.
To effectively deliver drug candidates, WP3 is interacting closely with WP1 and WP2 to identify and select potential starting points for further development based on clearly defined progression criteria. A screening cascade for (phenotypic) hit ID has been implemented and executed. In addition, a coordinated AI-platform and analysis of targets for their druggability is being finalized to facilitate the selection of potential starting points for chemistry. The medicinal chemistry efforts have not yet been initiated as the review and selection of potential starting points from the first wave of hit identification is still ongoing.
In addition to the Hit selection criteria to move forward into Hit to Lead (H2L), WP3 contributors have already prepared for the next steps by defining the initial progression criteria for hits, leads and optimized lead compounds. In addition, a screening cascade for H2L and lead optimization (LO) is proposed, including the flow for the ADMET-PK related assays. The aim is to work towards the predefined target product profiles (TPPs) which have also been discussed within WP3 and are close to finalisation.

Project Details:
Kniegelenkserkrankungen kommen bei Pferden regelmäßig vor. Bei der ultrasonographischen Untersichung ihrer Menisken entstehen akustische Artefakte, die mit krankhaften Befunden verwechselt werden können. In dieser Studie sollen ultrasonographische Befunde an Menisken von Pferden ohne Kniegelenkserkrankung mit anatomischen und feingeweblichen Befunden verglichen werden, um eine bessere Abgrenzung zwischen normalen Ultraschall-Befunden mit den üblichen akustischen Artefakten einerseits und pathologischen Veränderungen andererseits zu ermöglichen. Durch eine Einteilung der Präparate in verschiedene Lebensaltersgruppen wird zudem eine Einordnung alterungsbedingter morphologischer Veränderungen am Meniskus erwartet.

Results:

Geburek, F., Bodem, L., Staszyk, C.

Tears or Artifacts? Comparison between normal ultrasound and macro-anatomy of the medial femorotibial meniscus.

In: Scientific Abstracts of the 29th Annual Scientific Meeting of the ECVS. Vet. Surg. 2020, 49(S2), p. O195

https://doi.org/10.1111/vsu.13478

Cooperation Partners:

Prof. Dr. C. Staszyk, Institut für Veterinär-Anatomie, -Histologie und -Embryologie, Fachbereich Veterinärmedizin, Justus-Liebig-Universität Gießen

Project Details:
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Funding: Studienstiftung des Deutschen Volkes

Project Details:
We investigate the pathophysiological pathways underlying post-COVID-19 syndrome with the goal to develop biomarkers and rational therapeutic intervention.

Cooperation Partners:

Prof. Dr. Gülsah Gabriel (TiHo, HPI Hamburg), Prof. Dr. Günter Höglinger (Neurology, MHH), Prof. Dr. Ulrich Kalinke (TWINCORE Hannover)

Funding: DFG Collaborative Research Centre (SFB) 1270 (2017-2025) ?Electrically Active Implants? ELAINE.

Project Details:
Der dtsz Hamster ist ein hervorragend charakterisiertes Modell für die Dystonie, der Gendefekt ist jedoch nicht bekannt. Eine Identifikation des Effektes ist wichtig zum Verständnis der Pathophysiologie der Dystonie und zur Therapieentwicklung. In diesem Projekt werden Genom und Transkriptom des Modells sequenziert und auf Gendefekte hin untersucht.