Overview of research projects

Funding: Morris Animal Foundation, 62.488 EUR

Project Details:
We will investigate brain function, brain metabolism and gut microbiome in dogs to distinguish between epileptic seizures and a episodic movement disorder called paroxysmal dyskinesia - commonly mistaken for epileptic seizures - to improve diagnosis and appropriate treatment

Funding: Fritz-Ahrberg-Stiftung, 100.000 EUR

Project Details:
technique
Summary:
Hepatitis E virus (HEV) is an increasingly common food-associated cause of acute viral hepatitis. To ensure rapid pathogen identification and tracing of the infection sources, rapid and reliable detection methods are crucial. Various approaches are available for the detection of HEV, some of which involve considerable effort, such as cultivation of cell cultures or performing animal experiments. Loop-mediated isothermal amplification enables rapid pathogen detection with low-cost equipment and little work effort, qualifying the method for on-site application. Within the framework of the project a LAMP assay for detecting HEV in pork products and liver will be developed and validated. For this purpose, suitable genomic target regions will be identified and used for specific primer design. Assay validation includes analytical specificity and sensitivity testing as well as determining the detection limit in artificially contaminated matrices under the influence of product-typical background flora. Finally, the assay will be applied to natively contaminated samples to define the diagnostic quality criteria of the test procedure. In the second phase of the project, pig livers will be examined using the developed LAMP assay and classified into three categories according to viral load. Afterwards, liver sausages will be produced from this material and tested again so that conclusions can be drawn about the significance of the virus load in the raw material and influences of the production process on the viral load in final products.

Funding: Deutsche Forschungsgemeinschaft, 204.886 EUR

Project Details:
In this research project, systematic investigations on the development and the role of the immune response during Enterococcus cecorum infections in chickens will be conducted for the first time. Until now it is unknown, how the unspecific and specific immune system reacts on the infection.The results of this research project may be fundamental for the development of vaccines against this very important pathogen of broiler type birds.

Funding: Smithsonian Tropical Research Institute, Panama Secretaria Nacional de Ciencia y Tecnologia, Panama, 18.000 EUR

Project Details:
The evolution of different forms of parental care is an important topic in behavioral ecology, and it involves complex suites of associated parental and offspring traits. For example, some parents provide nourishment or selection and protection of suitable nesting sites for offspring. Understanding how memory guides individuals to locate or return to a reproductive resource is one of the major challenges in studies of animal behavior. During parental care, poison frogs routinely transport their tadpoles from terrestrial clutches to suitable deposition sites, and some individuals return to supply their offspring with nutritive unfertilized eggs. Thus, these frogs rely on spatial memory to exploit resources important for successful reproduction. However, it is unknown how the spatial abilities are related to the parental care traits performed by an individual. The aim of this study is to investigate behavioral spatial strategies and their genetic basis in the strawberry poison-dart frog, Oophaga pumilio. To investigate the spatial strategies in the context of parental care we aim examining ability of females and males to find a goal in a plus maze under experimental conditions. Moreover, we will determine the possible genes involved in spatial learning through gene expression analysis (RNASeq) of the pallium, the brain region known to be involved in spatial learning. Since females perform most parental care duties involving navigation in large home ranges, we expect females to have better spatial abilities than males.

Cooperation Partners:

Dr. Roberto Ibañéz, Ph. D., Smithsonian Tropical Research Institute

Prof. Dr. Klaudia Witte, Universität Siegen

Project Details:
The aim of this study is to examine a possible association between the
concentration of IGFBP and IGF-1 in blood and follicular fluid and whether this is also reflected in differences in local gene expression in the immediate vicinity of the oocyte. The IGFBP pattern in blood and follicular fluid of the same animals will be measured by Western ligand blotting and the IGF-1 concentration by ELISA. The local gene expression of components of the IGF system in obtained granulosa cells will be detected by PCR. Thus, a possible transfer between the somatotropic axis and the local IGF-1 system will be investigated and visualized by in vivo experiments.

Results:

https://elib.tiho-hannover.de/receive/tiho_mods_00007881

Cooperation Partners:

Martin-Luther-Universität Halle-Wittenberg

Funding: DFG, 310.150 EUR

Project Details:
The intermediate nuclei of the lateral lemniscus (INLL) is one of the three nuclei of the lateral lemniscus that process and relay auditory information between the cochlear nucleus, the superior olivary complex and the auditory midbrain. While the function of the other two lemniscal nuclei is at least partially understood the involvement of the INLL in sound processing is largely unknown. Moreover, the transmitter type of INLL neurons seem species specific, as rodents and bats are labelled for glutamatergic and glycinergic markers respectively. From animal models that hear well below and above 2 kHz, like humans, hardly any functional data from this auditory brainstem structure is available. The present anatomical and functional data of the INLL indicates that it might be involved in the integration of auditory information between different frequencies. Such a cross-frequency integration is key process for generating the neuronal representation of our auditory environment. To elucidate the filter functions and functional role of the INLL we propose to investigate the sound processing features of this auditory structure with in vivo single unit electrophysiology. Initially, we will record acoustically evoked responses elicited by a battery of sound stimulations ranging from pure tones to conspecific calls. This stimulation battery allows us to characterize the basic processing features of INLL neurons. In the next step, we will determine the temporal and frequency dependent integration characteristics of INLL neurons. Our preliminary in vivo single unit recordings highlight the temporal filter functions by analyzing modulation transfer functions of stimulated transposed tones. In agreement with existing data from bat, we find evidence for integration of sounds between different sound frequencies. Obtaining deeper insights into the filter functions and integration characteristics will allow us to postulate functional roles of the INLL in sound processing. Finally, we plan to perform whole-cell in vivo recordings to gain mechanistic insight how INLL neurons achieve their processing tasks. Thus, this application will illuminate the functional role of an auditory brainstem structure that is well connected but hardly understood and therefore the proposal will substantially add to our understanding of sound processing and how we generate our auditory world in our brain.

Funding: Deutscher Akademischer Austauschdienst (DAAD), 48.000 EUR

Project Details:
Alphaviruses (family Togaviridae) are emerging and re-emerging small enveloped RNA viruses, which are transmitted from animal reservoirs to humans by mosquitoes and can cause debilitating joint pain or encephalitis. Depending on the reservoir species and the transmitting
mosquito vector they are found in different geographic regions. While Chikungunya virus (CHIKV) and O?nyong?nyong virus (ONNV) were historically restricted to tropical and subtropical climates, Sindbis virus (SINV) and Ross River virus (RRV) are primarily found in Scandinavia and Australia, respectively. Adaptation of CHIKV to new mosquito vectors and global warming led to the occurrence of the virus in Europe, making it a potential public health problem in Germany and neighboring countries. An
introduction of Venezuelan equine encephalitis virus (VEEV), which is circulating in the Americas and causing neurological symptoms in equids and humans, may also be possible in the future. No human vaccines or antiviral drugs against arthritogenic and neurotropic alphaviruses are on the market to date. This is reflected by a gap of knowledge of the molecular mechanism of the infection process and critical host factors involved in alphavirus infection and cross-species transmission.
Recently, our team found that the phosphatidylserine receptor T-cell immunoglobulin and mucin domain 1 (TIM-1) is a CHIKV attachment factor. Another prominent group of phosphatidylserine receptors is the Tyro3, AXL, and MerTK (TAM) receptor tyrosine kinase (RTK) family comprising the three proteins Tyro3, AXL and MerTK. The physiological function of TIM and TAM receptors is to bind and internalize apoptotic
bodies, which expose phosphatidylserine on the outer membrane leaflet. We could show that TIM-1 but not AXL serves as host factor for CHIKV. Moreover, the TIM-1 phosphatidylserine binding domain termed metal ion ligand binding site (MILIBS) is critical for the host factor function of TIM-1 in the context of CHIKV infection. TIM-1 affects binding as well as internalization of CHIKV particles to human cells. Finally, TIM-1 also enhances CHIKV infection in keratinocytes, which are among the first target cells of the virus after mosquito bite.
We therefore hypothesize that alphaviruses including CHIKV will use phosphatidylserine receptors for cell attachment and entry in reservoir species such as non-human primates and in transmitting mosquito vectors. Moreover, we here aim to clarify if virus produced in insect cells also exposes phosphatidylserine and this aids in infection of human cells, i.e. in cross-species transmission. Lastly, we will elucidate, how
phosphatidylserine becomes exposed on the viral envelope.
Thereby the work will contribute to the understanding of the molecular composition of alphavirus particles, the function of alphavirus attachment factors and the role of apoptotic mimicry in cross-species transmission and consequently emergence of alphaviruses.

Funding: Verein der Förderer der Wildtierforschung e. V., 5.800 EUR

Project Details:
This dissertation project will first validate the non-invasive measurement of glucocorticoid metabolites (fGCM) as a stress indicator in the common buzzard (Buteo buteo) living in permanent housing. Subsequently, stress levels as well as microbial metabolic fingerprint will be determined in captive buzzards during the rehabilitation process to investigate the relationship between anthropogenic stress and changes in microbial metabolic activity in captive birds of prey. In conclusion the rehabilitation procedures in captive birds of prey will be evaluated and recommendations to optimize animal welfare will be developed.

Cooperation Partners:

Chadi Touma, Abteilung Verhaltensbiologie, Universität Osnabrück

Project Details:
Im Rahmen der Studien wird der Nachweis von Salmonellen im Rahmen des Mikrobioms untersucht, sowie der Einfluss externer und interner Faktoren auf die Ausscheidungsrate. Dabei wird auch der Einsatz von Phagen zur Beeinflussung der Salomonellenausscheidung geprüft.

Cooperation Partners:

RKI Wernigerode, Helmholtz-Institut Leipzig

Funding: Forschungskreis der Ernährungsindustrie e.V. (FEI), 96.588 EUR

Project Details:
Milk is increasingly criticised by the public for causing various diseases in humans. Beta-casomorphin-7 (BCM-7), which is formed from A1 beta-casein during the digestion of milk, is suggested to be responsible for this. Caseins make up the largest proportion of the protein fraction in milk, accounting for about 80% of the total protein. Four types are distinguished, two different alpha-caseins (αS1 and αS2), as well as kappa- and beta-casein. In domestic cattle, 12 different variants of the beta-casein gene (CSN2) are known so far (A1, A2, A3, B, C, D, E, F, G, H1, H2 and I), of which the A1 and A2 variants are the most significant. At the protein level, the A1 and A2 beta-caseins differ in a single amino acid at position 67 (A1: histidine; A2: proline), which is thought to have a significant influence on the structural and thus also functional properties of the proteins. These can influence both the enteric digestibility of the milk and the technological properties during milk processing. The majority of milk marketed in Germany contains varying amounts of A1 and A2 beta-casein and is referred to as A1 milk. A2 milk, on the other hand, comes from A2/A2 homozygous animals and may not contain A1 beta-casein. The BCM-7 produced from A1 beta-casein may be further degraded to BCM-5, both of which are thought to mediate their effects via - and µ-opioid receptors. In A2 milk, however, the production of these BCM peptides is supposed to be significantly lower, although this assumption is still questionable. In the proposed project, therefore, fundamental questions about the effect of BCM-7 and its occurrence (degradation, formation) in milk and milk products should be answered. Therefore in one part of the project BCM-7 will be added to milk before processing to cheese and yoghurt, in another part milk from A1/A1 and A2/A2 cows will be used for processing. At different steps within the production of the cheese and yoghurt BCM-7 contents will be analysed. In further investigations, physicochemical, sensory and microbiological analyses will be performed to determine the extent to which the different milk genotypes influence the quality of the specific milk products.

Cooperation Partners:

Lehrstuhl für Physiologie (Frau Prof. Cornelia Deeg), Lehrstuhl für Klinische Pharmakologie (Prof. H. Ammer) der Ludwig-Maximilians Universität München