Projects of the third cohort

Title of PhD project: Molecular identification of viral pathogens in formalin-fixed, paraffin-embedded tissues of dogs with non-suppurative encephalitis

PI: Wolfgang Baumgärtner

Hypothesis:

Viral genomic sequences obtained from archived canine formalin-fixed, paraffin embedded tissue of the central nervous system and will allow establishing a cause-consequence relationship between the detected known and unknown viral pathogen and pathological findings.

Aim and objectives:

The general aim of the project is further identify the viral cause of canine diseases of the central nervous system.

• By using conventional histology and immunochistochemistry of archived tissues from the last 6 decades to identify cases of non-supprative encephalitis of unknown origin
• Suspected virus infection will be further substantiated by applying double-stranded RNA or selected interferon stimulated genes specific antibodies and a probe specific for interferon β.
• Followed by ribonucleic acid extraction from the selected FFPE tissues, RT-qPCR using pan-genus primer and/or NGS. Alignment to reference genomes available in databases will be used to detect known viral pathogens and related unknown viruses
• Investigation of the pathogenesis of the discovered virus by studying cell tropism and the distribution of the virus in the host organism using in situ hybridization for the distribution of the pathogen

Title of PhD project: Investigations on the influence of a vasostatin-expressing canine distemper virus on canine histiocytic sarcoma cells in vitro and in vivo

PI: Baumgärtner

Hypothesis:

It is hypothesized that tumor cell infection with genetically modified canine distemper virus strain expressing vasostatin continue to replicate, spread and secret anti-angiogenic molecules.

Aim and objectives:

The aim of the present study is to evaluate the influence of a vasostatin-expressing canine distemper virus (CDV) strain on canine histiocytic sarcoma cells. This is considered to be a proof-of-concept study by using a genetically-modified pantropic virus with a specific neurotropism for future treatment approaches of canine neuroectodermal neoplasms.

The first aim is to evaluate the general influence of the genetically modified virus strain on canine histiocytic sarcoma cells (DH82 cells) and endothelial cells in vitro.

The second aim is to determine the therapeutic efficacy of this modified virus strain, dependent on the tumor microenvironment, in a murine xenotransplantation model of canine histiocytic sarcoma cells.

Title of PhD project: Pathogenetic investigations of Rift Valley fever (RVF) and canine distemper virus infection using canine and murine brain organoids/neurospheres

PIs: Kalinke/Baumgärtner

Hypothesis:

The in vitro cell tropism and virus spread of RFVF and CDV in murine and canine brain organoids/neurospheres depends on the host cell composition and the virus strain itself and mimics closely the in vivo situation.

Aim and objectives:

• Establishment, generation and characterization of murine brain organoids/neurospheres
• Establishment, generation and characterization of canine brain organoids/neurospheres
• Comparative evaluation of similarities and dissimilarities that are essential to establish CNS murine versus canine organoids
• Infection of murine CNS organoids/neurospheres with RVFV
• Infection of canine CNS organoids/neurospheres with various genetically modified canine distemper virus strains
• Isolation and molecular characterization of infected and non-infected cells using various tissue staining, microdissection and RNA sequencing techniques in selected established models.
• Comparative analysis of the in vitro data with in vivo findings

Title of PhD project: The role of complement genes in infectious diseases in various viral infections

PIs: Baumgärtner

Hypothesis:

Activation of complement genes show great similarities in acute and chronic virus infection regardless of the causing agent or the affected tissue

Aim and objectives:

The general aim of the project is identify complement activation in the acute and chronic phase of various viral disease.

• Transcriptome data of various virus infections such as SARS-CoV-2, Theiler´s murine encephalomyelitis virus (TMEV) and canine distemper virus (CDV) will be analyzed for increased or decreased expression of complement genes.
• Correlation between histological changes and complement expression pattern.
• SARS-CoV-2 transcriptome data of lung, trachea, nasal cavity and brain will be comparatively analyzed for similarities or dissimilarities of complement genes expression

• Findings will be substantiated by using immunohistology/immunofluorescence and/or in situ hybridization for complement proteins and genes, respectively, in affected tissues.

Title of PhD project: Impact of morbillivirus infections upon respiratory innate immunity and pathology in wildlife carnivores

PI: Beineke

Hypothesis:

Previous studies revealed that innate immune cells are able to carry morbilliviruses to facilitate cell-to-cell transmission in the respiratory tract and that restriction of antiviral signaling pathways of innate immune cells enhance virus release from the lung in canine distemper. In this project, the hypothesis will be tested, that morbilliviruses alter the respiratory innate immune system of wildlife carnivores, which enhances virus transmission and lung pathology. 

Aim and objectives:

The general aim of the project is to characterize the impact of morbilliviruses upon innate responses and the integrity of respiratory epithelial cells.

Specific objectives:

1. Generation and characterization of 3D-culture systems of different wildlife carnivore species
2. Analyses of morbillivirus infections upon respiratory tract cells of wild carnivores in vivo and ex vivo

Title of PhD project: Effect of trained innate immunity upon brain immunopathology following neurotropic virus infection

PI: Beineke

Hypothesis:

In this project, the hypothesis that trained innate immunity enhances antiviral immunity and neuroprotection in viral encephalitis is tested.

Aim and objectives:

The planned project aims to investigate the effect of Dectin-1/Syk/CARD9 pathway modulation in APC in the Theilervirus model.

Specific objectives:

• Investigation of trained innate immunity mediated effects upon APCs and the impact on TMEV infection in vitro

• Mechanistic studies to characterize the effects of trained innate immunity upon TMEV infection in vivo

Title of PhD project: Classification of novel detected viruses using text mining and machine learning

PI: Jung

Hypothesis:

We hypothesize that host range and pathogenicity of novel viruses can be predicted using supervised learning models with sequencing data as input. We assume that predictions can be made by classifying viruses first to known viromes, thus giving also insight into the interplay between viruses.

Aim and objectives:

The general aim of the project is to classify novel viruses to known viromes, i.e. communities of viruses related to certain hosts or tissues, based on similarity comparisons and machine learning. Data on virome compositions are regularly published in the context of NGS based analyses. Our approach will integrate the potential interplay between viruses of the same virome, and thus provides to predict potential recombination of viruses.

Specific objectives:

a) To build a database relating novel viruses and their sequences to host species and diseases/symptoms as training data for machine learning models.

b) To train and evaluate ML models.

c) To employ ML models to predict host range of novel detected viruses.

Title of PhD project: Single-cell deconvolution combined with bootstrap of bulk RNA-seq data from infection research

PI: Jung

Hypothesis:

We hypothesize that deconvolution of bulk RNA-seq data from infection research can provide detailed information about cell-type specific transcriptome changes upon infection. We also assume that deconvoluted data will help to better understand the diseased based on gene expression networks. Finally, we assume that bootstrap analysis can help to judge the uncertainty in results.

Aim and objectives:

The general aim of the project is to employ existing methods for mathematical deconvolution of bulk RNA-seq data from infection research to decipher infectious diseases on the molecular level.

Specific objectives:

a) To obtain cell-type specific transcriptome expression data from bulk RNA-seq data, and

b) to use these data to identify transcriptomic changes upon infections on the level of individual cell types.

c) To obtain modified gene expression networks in different cell types.

Title of PhD project: Immune modulatory activities of the MERS-CoV N protein and its role for the MERS-CoV pathogenesis in mice

PI: Volz

Hypothesis:

The hypothesis is that the MERS-CoV N protein functions as an immune evasion protein and upregulation of the host innate immune responses. In doing so, strong immune responses against the N protein might inhibit the outcome of severe and lethal disease.

Aim and objectives:

The general aim of the project is to characterize the role of the MERS-CoV-N protein in regulating host antiviral response and in the pathogenesis of MERS-CoV infection.

Specific objectives:

a) to analyze the activation of innate immune responses in different mouse strains after vaccination with recombinant MVA viruses expressing the MERS-CoV N protein in different conformations.

b) to comparatively analyze the activation of adaptive immune responses  after vaccination with different MVA-MERS-N

c) to comparatively evaluate the role of N protein during challenge infection.

Title of PhD project: Evaluation of innovative MVA-WNV candidate vaccines to overcome immunosenescence in old mice

PI: Volz

Hypothesis:

Reduced amounts of naive T and B cells and altered pattern of innate driven inflammation are major causes of immunosenescence. We will comparatively analyze immune responses in younger and older after MVA-WNV vaccination/ WNV challenge. We assess whether modification in the MVA-WNV candidate vaccines improve immunogenicity and efficacy in elderly.

Aim and objectives:

The main aim is to identify immunological patterns responsible for poor efficacy of vaccines and a more severe disease outcomes in elderly. The overall goal is to evaluate and improve immunogenicity and efficacy of MVA-WNV vaccines in elderly individuals.

Specific objectives:

a) Identification of immunological hallmarks between elderly and young individuals after MVA-WNV vaccination

b) Identification of immunological correlates of severe WNV infection in the elderly

c) Development of improved MVA-WNV vaccines for the elderly

Title of PhD project: Interplay of hepatitis E virus single nucleotide variants with the innate immune system of the liver

PI: Steinmann/Becher

Hypothesis: Characterization of host immune signatures of HEV variants - Are different HEV single nucleotide variants associated with different immune responses?

Aim and objectives:

The general aim of the project is to:

Specific objectives:

a) Identification of host immune signatures after infection with different HEV variants

b) Validation of identified hits by ectopic expression and knock-out of candidate restriction factors

c) Characterization of HEV pathology of viral variants in primary human hepatocytes

Title of PhD project: Development and characterization of a hepatitis E virus genotype 1 cell culture system

PIs: Steinmann/Becher

Hypothesis: Which compensatory mutation occur under HEV-1 passaging and can current antiviral treatments inhibit HEV-1 replication?

Aim and objectives:

Specific objectives:

• Adaptation of HEV-1 isolates to efficient growth in cell culture and determination of potential adaptive mutation for HEV-1 replication. Which compensatory mutation occur under HEV-1 passaging and what is their role in HEV-1 adaptation in tissue culture?

• Evaluation of antivirals against cell culture derived HEV-1 and modes of viral resistance. Can current antiviral treatments inhibit HEV-1 replication and are resistance mutation against the drugs emerging?

Title of PhD project:  Role of salivary gland tissue in infection of pigs with respiratory and intestinal viruses

PIs: Becher

Hypothesis:

We hypothesize that porcine salivary glands are susceptible to infection with respiratory and enteric viruses of pigs and significantly implicated in pathogenesis and spread of various porcine viruses.  Furthermore, it is hypothesized that porcine salivary glands may play an important role in evolution and interspecies transmission of zoonotic viruses including influenza viruses and Hepatitis E virus.

Aim and objectives:

The general aim of the project is to study the role of porcine salivary gland tissue in infection with respiratory and enteric viruses from pigs and other hosts to enhance our knowledge on tissue tropism, host range, pathogenesis, and virus-host interactions of these viruses.

Specific objectives:

a) to characterize the differentiated salivary gland epithelial cells and organoid cultures (cell markers, barrier function of 2D epithelium, amylase activity)

b) to determine the susceptibility of salivary gland epithelial cells to porcine respiratory viruses (influenza A virus, PRCoV), porcine enteric viruses (TGEV, Rotavirus), and selected viruses from other hosts (e.g. human and avian influenza A viruses, Hepatitis E virus)

c) to determine the viral growth kinetics and viral genome replication of selected viruses

d) to study innate immunity profiles and immune responses of primary salivary gland epithelial cells against selected viruses

Title of the PhD project: Pathological investigations on marine mammals to assess the virological pressures as indicator for changes in population health: Implications for management of viral diseases and marine mammals

PI: Beineke, Siebert

Hypothesis:

We hypothesize that the susceptibility to viral diseases in marine mammals in the North Atlantic is influenced by changes in their marine ecosystem and can therefore be used as a measure of environmental pressure and ecosystem health.

Aim of the study:

The general aim of the project is to investigate the prevalence of viral pathogens and the immune status of marine mammals in the North Atlantic collected over the last decades. Data will be combined with available data on habitat use and distribution patterns as well as environmental data and human activities. This will allow to understand spatial and temporal changes of the occurrence of viral diseases and their effects on marine mammal species.

Specific objectives:

a) Assessment of presence of viral pathogens and immunological status in marine mammals from the North Atlantic

b) Determination of spatial and temporal distribution patterns of viral pathogens in marine mammals

c) Combining information on human-induced environmental changes with the presence of viral pathogens in marine mammals

Title of PhD project:  Reassortant orthobunyaviruses in mammals and insects and the role innate immunity for pathogenicity and intervention strategies

PI: Becker

Hypothesis:

Reassortant viruses differ from parental strains in respect of infection efficiency and pathogenicity in mammalian and insect hosts.

This difference might be linked to innate immune recognition and/or differential immune activation

Aim and objectives:

The general aim of the project is to continue the analysis of factors responsible for the differential pathogenicity of reassortant orthobunyviruses in mammalian and insect hosts. Thus far we were able to prove, that reassortant between Batai and Bunyamwera orthobunyaviruses, specifically the reassortant Batunya orthobunyavirus show increased replication in some mammalian and decreased replication in insect cells. Furthermore, we were able to identify differential expression of several innate immune markers in mouse primary dentritic cells

Specific objectives:

a) Characterize the interaction of parental and reassortant viruses with the innate immune response

b) Characterize replication kinetics of parental and reassortant viruses in the animal model (wt and interferon knock-out mouse strains and different mosquito strains)

Title of PhD project: Influential factors for arbovirus transmission in Central and West Africa-EcoVir2

PI: Becker

Hypothesis:

In EcoVir, we targeted the question if genetic variability and bionomic differences in local mosquito vector populations influence arbovirus occurrence across countries in Central and West Africa.

Aim and objectives:

The general aim of the project is to:

Analyse the factors that influce vector abundance and vector competence of West and Central African mosquito populations for arboviruses

Specific objectives:

a) Competitive interactions among Aedes aegypti and Aedes albopictus

• Characterization of Aedes larval breeding container systems in the field
• Intra- and interspecific competition between Aedes albopictus and Aedes aegypti

b)  Vector competence of Aedes aegypti and Aedes albopictus from Benin, Ivory Coast and  Gabon for arboviruses

• Cultivate Aedes strains from all three countries in the laboratory
• Infection experiments of all colonies with DENV and CHIKV to compare vector competence indices (including infection, dissemination, transmission)
• Haplotype and insect-specific virus characterization for laboratory colonies

c) Genetic characterization and interaction of mosquito genetics with viruses

• Sequence analysis of the haplotype profiles and insect-specific viruses of field-collected samples and samples from our laboratory experiments (WP3)
• Tripartite interaction between mosquito haplotype, insect-specific virus detection, and arbovirus transmission (samples WP3)
• What are the implications of insect-specific virus co-infection on arbovirus transmission in Gabon, Ivory Coast and Benin

Title of PhD project: Role of adipose tissue as a silent reservoir for respiratory virus replication

PI: Gabriel, Rautenschlein

Hypothesis:

We hypothesize that adipose tissue may act as a silent virus reservoir for respiratory viruses beyond the respiratory tract.

Aim and objectives:

The general aim of the project is to: understand the impact of adipose tissue to support respiratory virus replication beyond the respiratory tract.

Specific objectives:

a) to analyze the ability of avian adipocytes to support respiratory virus replication

b) to analyze the ability of mammalian adipocytes to support respiratory virus replication

c) to establish intervention strategies that interfere with respiratory virus replication in mammalian adipocytes

Title of PhD project: Role of importin-α7 in influenza A virus ribonucleoprotein complex assembly and nuclear trafficking

PI: Gabriel

Hypothesis:

Importin-α7 may act as a chaperone in influenza A virus ribonucleoprotein complex assembly and thereby facilitate correct nuclear trafficking.

Aim and objectives:

In this proposal, we would like to shed light on the mechanisms involved in importin-α7 mediated host adaptation and pathogenesis in mammals. In particular, we would like to address the question whether importin-α7 is involved in the assembly of vRNPs, which are then actively transported into the host cell nucleus allowing efficient viral replication. These studies will provide new insights into the role of importins in vRNP assembly and nuclear trafficking as an essential step in the viral life cycle and pathogenicity in the mammalian host.

Title of PhD project: Evolution and ecology of RNA viruses in small mammals

PI: Ludlow, Siebert

Hypothesis:

We hypothesize that endemic RNA viruses in small mammals in Germany will display a propensity for cross-species transmission to related species.

Aim and objectives:

The general aim of the project is to study the evolution of ecology of RNA viruses in small mammals in Germany.

Specific objectives:

• Characterize the virome of several species of small mammals
• Perform serological studies to determine the population level seroprevalence of selected viruses with a documented propensity for cross-species infections
• Assess the zoonotic potential of a subset of RNA viruses present in small mammals

Title of PhD project: Role of the RSV glycoprotein in mediating entry and spread in epithelial cells

PI: Ludlow

Title of PhD project: Innate Immunity in Metapneumovirus infection

PI: Rautenschlein

Hypothesis: We hypothesize that AMPV may be controlled by the interferon system, specifically IFN-III, but also interferes with the upregulation of IFN allowing early virus replication. Subtypes may show differences in their immunomodulatory properties, which subsequently lead to variable virus load and lesion.

Aim and objectives:

The general aim of the project is to:

Understand the role of interferons and importins in AMPV infection.

Specific objectives:

a) to investigate the role of IFN type I and III in AMPV infection by using tracheal organ cultures (TOC) of KO and WT embryos with and without the addition of recombinant IFNs and IFN-signaling inhibitors.

b) to identify possible viral proteins involved in IFN stimulation and inhibition

c) to determine the role of importin-α isoforms in AMPV TOC infection and their possible involvement in the nuclear entry of the virus and IFN response.

Title of PhD project: Phenotypical and molecular characterization of short- and long- term tracheal lesions in the hamster following SARS-CoV-2 infection with special emphasis of the diffuse endocrine system.

PIs: Baumgärtner

Hypothesis:

It is hypothesized, that SARS-CoV-2 infection will have a short- and long-term effect on the trachea, either as a solitary independent manifestation or in combination with pulmonary lesions. Associated changes might show a manifestation either on the cellular and/or molecular level with special emphasis on the tracheal epithelium, the organ-specific diffuse endocrine system and ciliary damage and regeneration.

Aim and objectives:

Motile cilia are microtubule-based, hair-like projections on the luminal membrane of epithelial cells in conducting airways. Through their continuous wave-like beating, they evacuate mucus secreted by goblet cells, thereby contributing to muco-ciliary clearance (MCC). In this function, motile cilia are actors of the first-line defense against inhaled pathogens. Dysregulated cilia will have a long-term effect on MCC and predispose for further diseases. Similarly, the diffuse endocrine system plays an essential role in respiratory tract imbalances. However, underlying pathogenetic mechanisms are not well understoond neither in various organs nor in the trachea. Therefore the envisioned study will enhance our understanding of short- and potentially long-term effects of SARS-CoV-2 infection on tracheal damage and their contribution to PASC.

Title of PhD project: Glycoprotein (G) mediated immune evasion mechanisms of human and animal orthopneumoviruses and metapneumoviruses

PIs: Rimmelzwaan

Hypothesis:

The hypothesis is that the sG of hRSV and bRSV have either differential immunomodulatory properties suggestive of human immune adaptation or common immune evasive properties, underscoring their potential to cause cross-species zoonotic infections.

Aim and objectives:

The general aim of the project is to:

Assess the immunomodulatory properties and modes of action of sG of bRSV and hRSV and selected viral proteins of aMPV and hMPV.

Specific objectives:

a) Investigate the interaction between sG and immune receptors (TLR2/6, CLRs and CX3CR1) and the subsequent cellular response.

b) Compare these responses between sG’s derived from bovine and human RSV.

c) Assess immunomodulatory properties of selected viral proteins from aMPV and hMPV and compare with those of RSV.

Title of PhD project: New treatment options for peripheral tick-borne encephalitis virus infection

PIs: Kalinke

Title of PhD project: Virus discovery and characterization platform

PI: Osterhaus

Hypothesis:

Wildlife and domestic animal reservoirs host viruses that may start major disease outbreaks among wildlife, domestic animals and humans. Their discovery and characterisation, as well as identification of their potential host range and inter-species transmissibility among domestic animals and wildlife are key elements of epidemic/pandemic and epizootic/panzootic preparedness

Aim and objectives:

The general aim of the project is to:

Build on and expand the established VIPER-1&2 wildlife and domestic animal disease and aetiology monitoring in Germany and abroad.

Specific objectives:

• Continue and extend ongoing VIPER-1&2 wildlife and domestic animal sampling activities.
• Exploit and streamline TiHo’s molecular and biological virus discovery and characterization platforms.
• Evaluate the threat of newly emerging or identified viruses to animal and human populations

Title of PhD project:  Viral infections of the bovine placenta: role of innate immunity and mechanism of diaplacental transmission.

PI: Becher

Hypothesis:

It is hypothesized that both, innate immunity and cellular factors involved in viral entry and subsequent steps of the viral life cycle, contribute to efficient control of viral infections in the placenta. The planned project will contribute to a better understanding of host cellular mechanisms implicated in antiviral defense.

Aim and objectives:

The general aim of the project is to enhance our knowledge about the role and mechanisms of innate immunity in the bovine placenta implicated in antiviral defense and to improve our understanding of diaplacental infections with viral pathogens.

Specific objectives:

a) to study the innate immune response after apical and basolateral stimulus with dsRNA

b) to study the innate immune response after apical and basolateral infection with ncp and cp BVDV

c) to establish co-cultivation of bovine caruncular epithelial cells (BCEC) and trophoblast cells for further studies of mechanism diaplacental transmission of bovine pathogens.

Title of PhD project: Detection of complement factors in canine CNS disease with special emphasis on canine distemper encephalomyelitis

PI: Baumgärtner

Canine distemper is a highly contagious and immunosuppressive viral disease caused by canine distemper virus (CDV), an enveloped RNA virus of the family Paramyxoviridae. The susceptible host spectrum of CDV is broad and includes all families of the order Carnivora; the Canidae (dogs, foxes, dingos), Felidae (cats), Mustelidae (ferrets, minks, badgers, weasles) and Proconidae (raccoons). The most vulnerable age of dogs for CDV infection is 3-6 months. As a result of the epitheliotropic properties of CDV, organs containing epithelium such as skin, conjunctiva, urogenital and gastrointestinal tract are frequently affected. The infected animal shows several clinical manifestations ranging from the rare peracute to the most common acute and subacute form with and without nervous signs. In canine distemper encephalitis two major forms, polioencephalitis and leukoencephalitis, can be distinguished Polioencephalitis, including old dog encephalitis, inclusion body encephalitis and postvaccinal encephalitis is a rare finding of CDV infection and is predominantly associated with lesions of the cortex and brain stem nuclei. The restricted viral infection found in neurons and protoplasmic astrocytes is characterized by neuronal necrosis and. In contrary, distemper leukoencephalitis (DL) represents the most common CNS manifestation frequently associated with demyelination. Lesions of DL are frequently observed in the cerebellum and less frequently in the cerebral white matter and spinal cord. Additionally, demyelination is consistently found in fibre tracts adjacent the ventricles and within the cerebellar velum, cerebellar peduncles and optic tracts. DL can be categorized as acute, subacute noninflammatory, subacute inflammatory, chronic, and sclerotic plaques. The aim of the present study is to analyze the role of complement at the different phases of the disease at the light microscopic and molecular level.

Title of PhD project: Correlation of microglial morphology and their transcriptomic signature in TMEV-infected OT-I and OT-II mice with and without adoptive transfer of GFP/RFP expressing CD8+ and CD4+ T cells

PI: Beineke

Hypothesis:

Based on these results, it is hypothesized, that adoptively transferred T cells are able to interact with microglia within the CNS and have an impact on their morphology and their transcriptomic signature.

Aim and objectives:

This project aims to investigate the effect of an early (3 days post infection [dpi]) and a late (8 dpi) adoptive transfer of green (GFP) and red fluorescent (RFP) T- cells on the microglial morphology and transcriptomic data in TMEV- infected OT-I and OT-II mice. The contribution of CD8⁺ and CD4⁺ T cell subsets for viral clearance and course of clinical disease will be investigated individually as well as the general pathomorphology and immune response with special focus on microglia morphology and transcriptomic data.

Title of PhD project: SARS-CoV-2 infection associated nervous system lesions in K18-hACE2 mice

PI: Baumgärtner

Aims of the study:

Numerous studies in human patients as well as animal models of COVID-19 indicate that neurologic manifestations and vascular changes play an important role in the disease. Therefore, the aim of this PhD-project is to characterize the neuropathological findings following SARS-CoV-2 infection using the K18-hACE2 animal model, with special emphasis on vascular pathology and neurodegeneration. Moreover, the protective effect of vaccination on CNS pathology will be determined.

Title of the PhD project: Investigation of Potential Long-Term Effects of Viral Infections on Motor Function Impairment in Mouse Models of Parkinson’s Disease

PI: Kalinke

Hypothesis:
Understanding the processes underlying CNS or peripheral infection that result in the development of neurodegenerative diseases allows delineation of new treatment strategies.

Aim and objectives:
• Characterization of the effect of virus infections in mouse models of PD
• Behavioral studies with infected mouse models under BSL2 conditions
• Development of target strategies to prevent

Titel of the PhD project: Understanding the neuropathogenesis of Rift Valley Fever Virus (RVFV)

PI: Rimmelzwaan

Hypothesis:

Our hypothesis is that modulation of immune functions of major glial cells by RVFV viral proteins is critical in the neuropathogenisis of RVFV.

Aim and objectives:

The general aim of the project is to dissect the roles of viral and host factors in the neuropathogenisis of RVFV and to determine the possible mechanisms of RVFV encephalitis.

Specific objectives:

• Identify the primary targets of RVFV in the CNS.  
• Study the role of RVFV proteins on the immune function of primary glial cells and neurons
• Study the neuropathogenesis of RVFV using 2D- (transwell) and 3D- (organoids) model of CNS

Title of the PhD project: Phenotypical and molecular characterization of short- and long- term lesions in the nasal cavity in the hamster following SARS-CoV-2 infection with special emphasis of the diffuse endocrine system.

PI: Baumgärtner

Aim of the study:

The study is based on the hypothesis, that SARS-CoV-2 infection will have a short- and long-term effect on the nasal cavity, either as a solitary independent manifestation or in combination with pulmonary lesions. Associated changes might show a manifestation either on the cellular and/or molecular level with special emphasis on the nasal cavity  epithelium, the organ-specific diffuse endocrine system and ciliary damage and regeneration as well as associated immunopathological processes.