A nanobiophysical approach to elucidate target-cell killing by amoebic parasites

• Applicant: Professorin Dr. Christine Selhuber-Unkel
• Subject Area: Biophysics
• Term: from 2010 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 163864509

The killing of target-cells is a key mechanism for food uptake and digestion in amoebae. Whereas non-pathogenic amoebae kill target-cells only intracellularly upon ingestion, parasitic amoebae, such as Entamoeba histolytica and Acanthamoeba, also kill target-cells extracellularly with a rapid contact-dependent “killing kiss” by exocytosis of membrane-active factors. This process is medically highly relevant because it causes significant morbidity and mortality. Studying the molecular and cellular mechanisms of target-cell killing is an important step towards understanding the antimicrobial responses and the pathogenicity of amoebae.The goal of this project is to reveal the principles responsible for the killing of target-cells by E. histolytica and Acanthamoeba castellanii. We will study the killing process from the initial contact between amoeba and target-cell to the final killing of the target-cell using an interdisciplinary approach, where nanobiophysical methods will be applied.The core aims of the project are to investigate the adhesion between amoebae and targetcells, to identify the molecules responsible for initiating the extracellular killing machinery, to characterize the dynamics of target-cell killing and uptake, and to quantify the role of mechanical force for target-cell death. We will complement force measurements by optically monitoring cellular elements with high spatial and temporal resolution, so that finally conclusions on the interplay between physical and biochemical mechanisms for target-cell death can be drawn.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: Spinning disc Mikroskop
• Instrumentation Group: 5040 Spezielle Mikroskope (außer 500-503)