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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Cellular responses to meningococcal meningitis

Tildelt: kr 3,4 mill.

Meningococcal disease is a leading cause of meningitis and septicaemia worldwide. Among the serious consequences of meningitis are brain edema and disturbed neuronal excitability. These effects are often the direct cause of death. Despite the serious comp lications, the molecular basis for these events is not known. We will study the interaction of meningococci with host cells in glial cellular assays and mice models. Animals will be subjected to intraspinal injection of meningococci to delineate the patho genesis of bacterial meningitis. We will employ a combined functional genomics and mice model approach to assess which components in glial cells are effected during the infection process. In this context we will focus on the expression of aquaporins (Aqp- 4) and selected neurotransmitter receptors and transporters. The effect on host responses will also be monitored in transgenic mice with immunological defects. In addition, we will employ microPET imaging to assess the infection process quantitatively in real time. The combination of meningococcal virulence and DNA repair mutants with murine models and microPET imaging represents a novel approach to study the meningitis process. Understanding these mechanisms is vital to the management of important pathog ens and the search for new vaccine candidates and drug design. The results are expected to yield new information on meningococcal meningitis and brain edema, with significant potential for discoveries that can directly influence and inspire new strategies for prevention and treatment of this serious disease.

Budsjettformål:

FRIMEDBIO-Fri prosj.st. med.,helse,biol