Research

Funding: DFG (Heisenberg), 256.200 EUR

Project Details:
The objective of this research work is to evaluate the genetic architecture of body size using a pig model in a multi-omics approach. It particularly aims at in-depth investigations of interrelations of size determining variants, transcriptional variation among miniature and large size as well as the identification of topologically associated domains (TADs) and putative enhancers involved in body size determination. This study is particularly focusing on the elucidation of the regulatory landscape in pigs and its essential role in the determination of body size.Initial analyses of whole genome sequencing data of miniature versus standard sized breeds/populations are supposed to identify potential signatures of selection reflecting high selection pressures in both directions- miniature and large size- harboring variants causative for the miniaturization across-breeds. Subsequently, I aim at detecting chromatin interactions defined as TADs and putative enhancer elements in the region of these variants involved in size-determination by targeting high intensity peaks of chromatin interactions from Hi-C analysis as well as high histone modification levels associated with active enhancers (H3K27ac and H3K4me1) from ChIP-seq in the growth plates of the long bones. These marks of active DNA sequences will then be linked to transcriptional variation in-between miniature and large pigs. An in vitro model will be established for further functional validation.This will be the first study investigating genomic and functional effects on body size specifically targeting growth plates in pigs. Based on these data, we aim at increasing the knowledge of biological processes in mammals regulating growth and determining the size of a body. This profound understanding of body size development will not only be of high importance for livestock breeding but will also provide better understanding of growth biology, developmental genetics and disturbances in growth processes.

Results:

https://link.springer.com/article/10.1186/s12864-022-08801-4

Cooperation Partners:

Prof. Dr. Stefan Mundlos, Max-Planck-Institut für Molekulare Genetik, Berlin

Funding: DFG, 466.350 EUR

Project Details:
The objective of this research work is to evaluate the genetic architecture of body size using a pig model in a multi-omics approach. It particularly aims at in-depth investigations of interrelations of size determining variants, transcriptional variation among miniature and large size as well as the identification of topologically associated domains (TADs) and putative enhancers involved in body size determination. This study is particularly focusing on the elucidation of the regulatory landscape in pigs and its essential role in the determination of body size.Initial analyses of whole genome sequencing data of miniature versus standard sized breeds/populations are supposed to identify potential signatures of selection reflecting high selection pressures in both directions- miniature and large size- harboring variants causative for the miniaturization across-breeds. Subsequently, I aim at detecting chromatin interactions defined as TADs and putative enhancer elements in the region of these variants involved in size-determination by targeting high intensity peaks of chromatin interactions from Hi-C analysis as well as high histone modification levels associated with active enhancers (H3K27ac and H3K4me1) from ChIP-seq in the growth plates of the long bones. These marks of active DNA sequences will then be linked to transcriptional variation in-between miniature and large pigs. An in vitro model will be established for further functional validation.This will be the first study investigating genomic and functional effects on body size specifically targeting growth plates in pigs. Based on these data, we aim at increasing the knowledge of biological processes in mammals regulating growth and determining the size of a body. This profound understanding of body size development will not only be of high importance for livestock breeding but will also provide better understanding of growth biology, developmental genetics and disturbances in growth processes.

Results:

https://link.springer.com/article/10.1186/s12864-022-08801-4

Cooperation Partners:

Prof. Stefan Mundlos, Max-Planck-Institut für Molekulare Genetik, Berlin

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: LJB e.V. Landesjägerschaft Bremen, 10.919 EUR

Project Details:
The wildlife data (WTE) for the Hanseatic City of Bremen is collected by the Landesjägerschaft Bremen e.V. (LJB) in cooperation with the Landesjägerschaft Niedersachsen e.V. (LJN). Employees of the LJN and the TiHo maintain the WTE Lower Saxony database, which is also made available by the LJN to the LJB for the WTE-HB data. The LJB provides the TiHo with data from the WTE-HB for analysis and publication within this research project.
In addition to descriptive statistics on population development, multivariate statistical analyses are used to determine the influencing factors. These factors are then used to make forecasts for the future. The exact statistical methods to be used can only be decided on the basis of the data available.

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: 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:
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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)