Information
MICH is specialized in the study of picornaviruses. Being a leading poliovirus lab, interest also exists in rhinoviruses and viruses at the origin of Theiler's murine encephalomyelitis (TMEV). As major causes of the common cold, rhinoviruses are an economically important group of viruses. the knowledge acquired with the study of poliovirus enables us to gather fundamental insights in the replication cycle of rhinoviruses, necessary for the identification of new drug targets. Moreover, we also screen compounds on their antipicornaviral activity and elucidate their mechanism of action. All phases of the picornaviral replication cycle can be studied, both involving classical techniques (e.g. plaque assay, radiolabelling, immunoprecipitation, SDS-PAGE, ultracentrifugation) as well as advanced techniques such as real-time PCR and capillary electrophoresis. The research is conducted in an in vitro setting using susceptible cells as well as cell-free replication systems, resulting in more flexibility compared to animal models.
TMEV, a picornavirus that induces multiple sclerosis in mice (MS), is studied in the context of viral persistence, being at the basis of the demyelinating disease. Our aim is to reach a better understanding of the molecular mechanism of TMEV persistance using a recently established, persistently TMEV-infected macrophage cell line in combination with cytokine profiling.
Actually, based on previously obtained quantitative RT-PCR data in blood and cerebrospinal fluid from patients with (non)-neurological diseases, the group is also developing a pan-viral DNA microchip capable of detecting viral sequences in biological samples of patients with a suspected viral infection or a disease associated with a viral infection such as MS, amyotrophic lateral scelrosis or diabetes.
Solutions to deal with key bottlenecks in the pharmaceutical R&D process, offered by MICH, consist of:
Predictive Pharmacology:
- in vitro screening of new compounds in a cell-free system and a persistently TMEV-infected macrophage cell line; determination of the mechanisms of action
- evaluation of existing compounds
- unraveling of the mechanism of TMEV persistence
- unraveling of new antipicornaviral drug targets
Biomarkers:
- identification of viral persistence-related biomarkers: cytokines, chemokines, etc
- effect of antipicornaviral compounds on identified biomarkers
- identification of viral genome sequences in samples of MS patients
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