All research projects

Funding: DFG- Deutsche Forschungsgemeinschaft, 456.829 EUR

Project Details:
PREGROW-project aims to provide a single nuclei transcriptional profile of the pituitary and its downstream targets in miniature-sized and larger-sized pigs as a model for prepubescent growth control. This approach is meant to meet a big challenge we encounter in research work on growth: Body size is a whole-organism phenotype with many different tissues involved, and the variant effects are expected to be complex. For this reason, PREGROW aims at studying the genetic landscape of growth-axis-related tissues in the pig, providing a genetic resource for deciphering mechanisms of gene interplay, and underlying variant effects. The objective is to perform a functional trait-cell type enrichment for previously identified genome-wide associated growth and height loci obtained from GWAS by assigning them to cell types identified in gene expression data on single nuclei level. The project aims at identifying those genes, which are differential in large versus miniature pigs, and can thereby be considered as important fine-regulators of prepubescent growth in pigs, in addition to the known hormonal axis regulation by growth hormone/IGF.

Cooperation Partners:

Prof. Malte Spielmann, Universität zu Lübeck

Funding: Industry (Animal breeding), 1.056.339 EUR

Funding: Industry (Stable equipment/Animal husbandry supplies), 196.665 EUR

Project Details:
Sensor-based devices are increasingly used to objectify lameness and other gait abnormalities in horses. Recording the ground reaction forces of the hooves is the gold standard but measurements require well equipped facilities and significant effort. With the help of pressure boots, which can be easily attached to the horse's hooves, their pressure on the ground and position during locomotion can be determined. Data will be compared to established kinetic (pressure measuring plate) and kinematic methods (Equinosis Lameness LocatorTM).

Results:

Keller, J., Jung, K., Geburek, F. Equine Lameness Detection and Monitoring with an Instrumented Hoof Boot.

In: Proceedings of the 5th Scientific Meeting of the European College of Veterinary Sports Medicine and Rehabilitation, ECVSMR; Cordoba, Spain, October 16-18, 2024; in print

 

Geburek, F., Jung, K., Keller, J. Bewegungsanalyse mit instrumentierten Hufschuhen - was ist möglich?

In: Tagungsband des DVG-Vet-Congress 2024 - 7. Internationaler Kongress zur Pferdemedizin / Tagung der DVG-Fachgruppe Pferdekrankheiten, 1.- 2. November 2024, Berlin, Verlag der DVG Service GmbH, Gießen, ISBN 978-3-86345-736-5, S. 44-46

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

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, 299.200 EUR

Project Details:
Marked climatic oscillations between glacial and interglacial periods had worldwide consequences for vegetation as well as animal population dynamics. The importance of these shallow-time (on geological and evolutionary timescales) geographic dynamics for shaping current biodiversity and biogeography patterns is increasingly stressed, although rarely analyzed in an innovative integrated manner. One of the necessary steps in order to understand the drivers of biodiversity is to synergize the efforts from various research fields by, for example, reconstructing the interplay between the degree and frequency of historic forest cover changes and demographic changes of forest-dependent organisms. This study aims to integrate validated records of vegetation and climate dynamics with inferred population dynamics to reconstruct the dynamics of forest landscapes and of populations of forest dwelling species over space and time in a primate model endemic to Madagascar. Madagascar developed a unique biodiversity during its long isolated history. Despite the long-lasting interest in the natural history of the island, much is still unknown about the biodiversity dynamics and long-term ecology of this continental island. This multidisciplinary project aims to integrate demographic inferences based on molecular datasets of mouse lemurs with validated high resolution vegetation dynamics based on paleoecological reconstructions obtained from the same study sites reaching back to the Last Glacial Maximum (LGM). To reach these goals, study sites in northwestern and northern Madagascar were visited for the joint collection of (paleo)ecological and population datasets and samples of mouse lemurs in direct vicinity to each other. For the paleoecological part sediment cores from lakes were drilled and complemented with samples of modern pollen rain and vegetation data. The sediment cores are subjected to temporal high-resolution pollen and charcoal analyses, radiocarbon dating and multivariate modelling of the vegetation and climate dynamics over time and space. The lemur samples are analyzed by applying RADSeq and NextSeq sequencing techniques on various subsets of samples. This study will contribute substantially to a deeper understanding of the evolutionary history and future prospects of lemur populations in view of ongoing habitat fragmentation and future climate change.

Results:

Montade, V.; Bremond, L.; Teixeira, H.; Kasper, T.; Daut, G.; Rasoamanana, E.; Pamavovolona, P.; Favier, C.; Arnaud, F., Radespiel, U.; Behling, H. (2024): Montane rain forest dynamics under changes in climate and human impact during the past millennia in northern Madagascar. R. Soc. Open Science, 11, 230930. https://doi.org/10.1098/rsos.230930.

 

Teixeira, H; Salmona, J; Arredondo, A.; Mourato, B; Manzi, S.; Rakotondravony, R.; Mazet, O; Chikhi, L.; Metzger, J; Radespiel, U. (2021): Impact of model assumptions on demographic inferences - the case study of two sympatric mouse lemurs in northwestern Madagascar. BMC Ecol. Evol. 21, 197. https://doi.org/10.1186/s12862-021-01929-z.

 

Teixeira, H.; Montade, V.; Salmona, J.; Metzger, J.; Bremond, L.; Kasper, T.; Daut, G.; Rouland, S.; Ranarilalatiana, S.; Rakotondravony, R.; Chikhi, L.; Behling, H.; Radespiel, U. (2021): Past environmental changes affected lemur population dynamics prior to human impact in Madagascar. Comm. Biol. 4, 1084. https://doi.org/10.1038/s42003-021-02620-1.

Cooperation Partners:

Prof. Hermann Behling, Universität Göttingen

Dr. Vincent Montade, Universität Montpellier, Frankreich

Dr. Lounès Chikhi, IGC, Oeiras, Portugal

Dr. Jordi Salmona, Universität Toulouse, Frankreich

Prof. Solofonirina Rasoloharijaona, Universität Mahajanga, Madagaskar

Dr. Romule Rakotondravony, Universität Mahajanga, Madagaskar

Funding: Bundesministerium für Ernährung und Landwirtschaft (BMEL), 622.484 EUR

Project Details:
Ziel des Projektes "Evolection" ist, die Züchtungsarbeit von nach dem Prinzip der Wechselkreuzung arbeitenden, selbstremontierenden Sauenbetrieben zu objektivieren und durch eine verbesserte Selektionsentscheidung aufgrund von im Betrieb automatisch erhobenen Massendaten zu optimieren. Mittels Cloud-basierter Datenanalyse von in Sauenbetrieben erhobener Leistungszahlen und der Massendatenanalyse verschiedenster Sensordaten des Betriebs im Sinne eines KI-Systems wird ein objektiv nachvollziehbarer und für jeden Transparenter "Goldstandard-KI" der Züchtungsselektion bei der Schweinezucht mittels Wechselkreuzung etabliert. Damit wird die "züchterische Nase" erfahrener Züchter softwaretechnisch nachgebildet, objektiviert und über die Cloud jedem praktischen Sauenhalter zugänglich gemacht. Auch wird durch die Etablierung neuer Bewertungsparameter wie "Langlebigkeit" und "Mütterlichkeit" der gesellschaftlichen Forderung nach mehr Tierwohl Rechnung getragen und durch die messtechnische Erfassung und Auswertung der Futterverwertung, die Ressourceneffizienz der Schweinehaltung als Gesamtheit verbessert.

Cooperation Partners:

Hölscher + Leuschner GmbH & Co. KG

Funding: Europäische Kommission, 252.788 EUR

Project Details:
Spinal Muscular Atrophy (SMA) is a monogenic motoneuron disease with a neuromuscular phenotype resulting in infant death in severe cases. Besides motoneurons in the central nervous system (CNS), there is growing evidence of an involvement of peripheral organs. SMA is caused by reduced Survival of Motoneuron (SMN) protein levels and SMN is ubiquitously expressed. Therefore, SMA patients show reduced SMN levels also in peripheral organs. A restoration of SMN levels in the CNS is a potent therapeutic strategy which led to the approval of two different compounds: Spinraza is an antisense oligonucleotide which increases SMN mRNA, Zolgensma is an adeno-associated virus increasing expression of SMN. However, both strategies focus on the restoration of CNS SMN levels without a sustainable effect on peripheral organs. In 2020, approval of a third drug, Risdiplam, a systemic SMN enhancer, is expected. Although patients greatly benefit from a treatment of the neuromuscular phenotype they face a precarious future: there is no comprehensive landscape of vulnerable organs and no approved treatment for the periphery. We will analyze intrinsic defects in peripheral organs (WP1), evaluate the organ specific molecular and cellular functions of the SMN protein in relevant organs (WP2), and translate these findings to SMA patient derived models, which we will treat with a systemic SMA drug currently under clinical evaluation (WP3). The SMA field involves stakeholders, which allow early stage researchers to personally interact with basic scientists, clinicians, pharmaceutical companies and patient organizations. For our training network, we will combine this vertical integration with a broad perspective on multiple organ systems in SMA. The training strategy assures career options and employability of early stage researchers beyond the SMA field. We will go beyond the motoneuron and identify organs, mechanisms and molecules that could be targets for the peripheral aspects of SMA.

Cooperation Partners:

Prof. Dr. Peter Claus (Medizinische Hochschule Hannover)

Funding: Niedersächsisches Minsiterium für Wissenschaft und Kultur, 201.000 EUR

Project Details:
Das vom Niedersächsischen Minsiterium für Wissenschaft und Kultur geförderte Projekt wird über die integrative Analyse von Transkriptom-Datensätzen zu einem besseren Verständnis der zugrundeliegenden Mechanismen der Lungenfibrose und hieraus ableitbarerer therapeutischer und diagnostischer Strategien führen. Das interdisziplinäre Konsortium mit Partnern der TiHo, der MHH und des Frauenhofer ITEMs verbindet klinische und molekularbiologische Expertise mit bioinformatischen Kompetenzen. Das ermöglicht die Integration von Daten aus der neuartigen Technologie der RNA-Sequenzierung auf Einzelzellebene. Das Projekt verspricht, neue Instrumente zur verbesserten Diagnostik und Therapien der Lungenfibrose zu entwickeln.

Cooperation Partners:

Dr. Davide DeLuca (Medizinische Hochschule Hannover), Prof. Dr. Antje Prasse (Medizinische Hochschule Hannover), Dr. Sylvia Escher (Fraunhofer Institut für Toxikologie und Experimentelle Medizin, Hannover), Dr. Jeanette Koschmann (geneXplain GmbH, Braunschweig)

Funding: DFG, 329.905 EUR

Project Details:
The VIPER research and training program will cover the global chain of events involved in virus emergence, all the way from virus discovery, isolation, molecular characterization, surveillance, and pathogenesis, towards animal and public health impact and intervention strategies including new approaches for prevention and control.

The VIPER research projects are subdivided into three pillars:

virus discovery, host range and transmission
virus-host cell interactions and pathogenesis, and
immune interference and intervention strategies.