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Current Projects

C-type lectin receptor-mediated effects on neurodegeneration and immunopathology in the brain following neurotropic virus infection

The Theiler’s murine encephalomyelitis virus (TMEV) represents a reliable experimental mouse model to study neurodegenerative processes and seizures induced by neurotropic viruses. Antigen presenting cells (APCs) account for the initiation of neuroinflammation and neuronal damage in infected C57BL/6 mice. Activating and inhibiting C-type lectin receptors (CLRs) are pattern recognition receptors on APCs that tightly control immune homeostasis and protective immunity in different infectious disorders; however, their function in TMEV infection remains undetermined so far. Based on the hypothesis that dysregulated CLR activation causes brain immunopathology and neurodegeneration, the planned project aims to analyze the effect of CLRs in the neuropathogenesis of TMEV infection in detail. Therefore, (1) viral and/or host specific ligands will be identified and (2) mechanistic studies will be performed to determine the function of CLRs in TMEV-infected mice. Results will help to understand the underlying mechanisms of neuroprotection and initiation of degeneration in viral encephalitis and will give detailed insights in the regulation of innate immunity in infectious disorders of the central nervous system.

 

     Projektverantwortliche:
Prof. Dr. Bernd Lepenies; Prof. Dr. Andreas Beineke
     Laufzeit:
März 2018 bis Februar 2021
     Drittmittelprojekt, gefördert durch DFG

Role of the C-type lectin receptors SIGNR3, MICL and DCIR in the recognition of plasmodial ligands and their contribution to the pathogenesis of cerebral malaria

Malaria is a major global cause of death from infectious diseases, resulting in more than 200 million clinical cases and more than 600.000 deaths per year. A fatal complication is cerebral malaria that causes neurological symptoms in affected patients. Whereas the role of adaptive immunity in the development of cerebral malaria has been analyzed quite in detail, little is known about the contribution of innate immunity to cerebral malaria induction. To date, most studies have focused on the role of Toll-like receptors in this process. In contrast, almost no studies have investigated whether and how C-type lectin receptors (CLRs) affect the course of malaria. CLRs belong to a family of lectins that recognize carbohydrate structures on pathogens such as viruses, bacteria, fungi, and parasites, thus they are involved in the initiation of immune responses. In own preliminary work, it was shown that CLRs contribute to Plasmodium recognition and may indeed play essential roles in cerebral malaria development. In the first part of the proposed project, distinct plasmodial ligands of the CLR SIGNR3 will be identified and characterized biochemically. In the second part, mechanistic studies will reveal how the CLRs SIGNR3, MICL, and DCIR impact the course of cerebral malaria. In summary, this project aims at elucidating how CLRs recognize plasmodial ligands and affect malaria pathogenesis.

 

Projektverantwortliche:
Prof. Dr. Bernd Lepenies
     Laufzeit:
Ende 2020 bis Ende 2023
     Drittmittelprojekt, gefördert durch DFG

Tailor-made glyco-optimized influenza virus vaccines

The goal of the proposed project is to understand the influence of glycosylation patterns on the efficacy of influenza viral vaccines and to use these insights to glyco-optimize vaccines. Specifically, we propose: (1) to propagate influenza viruses in different host systems and to analyze the glycosylation patterns of the viral glycoproteins; (2) to screen for virus variants with optimal (i.e. highly immunogenic) glycosylation patterns using in vitro and in vivo assays; and (3) to glyco-engineer host cell lines as a first step towards tailor-made glyco-optimized viral vaccines.

 

     Projektverantwortliche:

Dr. Guillaume Goyette-Desjardins

     Laufzeit:

Januar 2019 bis Dezember 2020

     Drittmittelprojekt, gefördert durch Fonds de recherche Nature et technologies Québec

Diverse projects on vaccine design

     Projektverantwortliche:

Prof. Dr. Bernd Lepenies

     Laufzeit:

März 2018 bis Ende 2020

     Drittmittelprojekt, gefördert durch Industrie (Veterinärpharmazeutika und Impfstoffe)

Kontakt
Prof. Dr. Bernd Lepenies
Tel.:+49 511 953-6135
Fax.:+49 511 953-82 6135
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