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New insights by live cell microscopy: Heidelberg University Hospital Scientists discover key protein for the “birth” of malaria parasites and hint at the function of their native curvature.
The biology of the malaria parasite, named Plasmodium, is still poorly understood and many questions about cellular processes remain unanswered. To solve these open questions the group of Prof. Friedrich Frischknecht at the Centre of Infectious Diseases of Heidelberg University Hospital paves new avenues: The scientists used live cell microscopy of the unicellular parasite with their unique curvature to film their “birth” in the mosquito, their migration in vivo as well as in artificial mazes with different obstacles. The new insights gained from these experiments were recently published in “eLife” and „Advanced Healthcare Materials“.
“Hatching” of malaria parasites needs the collective effort of all parasites within a developing unit, named oocyst. This discovery was made by Dennis Klug, a PhD student in the group of Prof. Frischknecht when he investigated the previously undescribed protein Trp1. He infected mosquitoes with genetically manipulated parasites that were not longer able to produce Trp1. These parasites couldn’t egress from their oocysts at the midgut wall of the mosquito. But why? Night after night Klug and Frischknecht observed the processes within oocysts and filmed the “birth” of the parasites. Once the development within the oocyst is completed the parasites start to move in a synchronous manner. This ballet-like choreography seems to exert a much larger force on the wall of the oocyst than a single parasite could ever achieve – ultimately the wall ruptures. If Trp1 is lacking the parasite are not longer able to start their choreography. But this is not caused by a movement disorder – mechanically released from the oocyst the parasites could still move normally. “This suggests that Trp1 could act as a sensor that triggers synchronous movement within the oocyst”, says Klug. “Further experiments are needed to show how Trp1 functions in detail.”
Plasmodia are transmitted by mosquito bites to human or animals. During their further journey the parasites traverse the skin to enter blood vessels, invade liver cells and finally infect red blood cells. Within the skin the parasites move very fast to reach their next destination: blood vessels. Studies so far have shown that the parasites are not chemically attracted to blood vessels but appear to rapidly find them in an accidental manner. How they are able to do this is still not understood. Maybe the unique curvature of the parasite has something to do with this mechanism, the scientists from Heidelberg hypothesized. The transmissive stage of the malaria parasite has the shape of a crescent moon and based on this shape they are mostly moving in a circular manner if placed on a solid substrate. “The diameter of this circle corresponds to the diameter of the smallest blood vessels in the skin” notes Prof. Frischknecht. “We believe that this is no coincidence.” To test this hypothesis the team of Prof. Frischknecht together with scientists in the group of Prof. Joachim Spatz at the Institute for Physical Chemistry of Heidelberg University and the Max-Planck-Institute for Medical Research engineered an artificial maze with obstacles made of rods. These rods can be variied in their diameter to mimic differently sized blood vessels. The results of this experiment: When rods with different diameters were offered the parasites preferred rods that resembled their native curvature. “It seems that the parasite is made to move around the thinnest blood vessels in the skin, which are exactly those it enters. We and others could already film this behaviour in the mouse ear” tells the parasitologist. “This could explain how the parasite finds small weakenings in the vascular wall that might function as entry sites. We want do investigate this in more detail within a research project of the collaborative research center SFB 1129.”
Links to the media:
Literatur:
• Klug and Frischknecht, Motility precedes egress of malaria parasites from oocysts, eLife, 2017;
http://dx.doi.org/10.7554/eLife.19157
• Muthinja, Ripp, Hellmann Haraszti, Dahan, Lemgruber, Battista, Schütz, Fackler, Schwarz, Spatz and Frischknecht, Microstructured blood vessel surrogates reveal structural tropism of motile malaria parasites, Advanced Healthcare Materials, 2017; http://dx.doi.org/10.1002/adhm.201601178
Further informations:
Centre for Infectious Diseases, Parasitology: https://www.klinikum.uni-heidelberg.de/About-us.6570.0.html
http://www.sfb1129.de/
Contact:
Prof. Dr. Friedrich Frischknecht
Centre for Infectious Diseases, Parasitology
Tel.: 0049 6221 56-6537
E-Mail
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