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Mammalian-bacterial cell interaction: the role of sphingolipids, and a novel investigate approach

20th national competition for scientific and technical research

Intercellular Dialogue and Interactome: Pathological Implications

Senior Researcher : Félix María Goñi Urcelay

Research Centre or Institution : Instituto Biofisika. CSIC. UPV/EHU. Vizcaya

Abstract

The sphingolipid signalling pathway provides a response to cellular stress situations, starting from the hydrolysis of sphingomyelin by acid sphingomyelinase, yielding ceramide, and ultimately leading to apoptosis. Bacterial infection is an important cause of stress, arising from the interaction between the prokaryotic and eukaryotic cell, in which sphingolipids such as sphingomyelin and ceramide are being found to play a very important role. The axis ‘acid sphingomyelinase – ceramide’ has been proposed as a therapeutic target for infection treatment. A novel approach in the study of this pathophysiological process is hereby proposed, consisting of the use of mutant mammalian cells unable to synthesize sphingolipids, to explore the minimal sphingolipid requirements and metabolic changes that trigger the ceramide-dependent apoptotic response. Cells infected by Neisseria meningitidis or Staphilococcus aureus will be the main object of the present study. The investigation makes use of a combination of cellular, lipidomic and biophysical techniques (fluorescence, atomic force microscopy). In the first year of the project we have carried out studies on the hydrolysis of sphingomyelin by sphingomyelinase, to generate ceramide in cell membranes, and we have also studied the physical properties of sphingomyelin ± ceramide in fluid lipid bilayers of phosphatidylcholine.

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