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New Publication: Microtubule number and length determine cellular shape and function in Plasmodium
Posted May 29 2019
AG Frischknecht from the Department of Infectious Diseases at University Hospital Heidelberg investigated the role of microtubules in malaria parasites.

Malaria-causing Plasmodium parasites are a major threat for humans in tropical countries. To better understand how these parasites function (and in the hope to develop new strategies to kill them) scientists use different microscopic and gene engineering techniques.

In their new publication, the group of Friedrich Frischknecht from the Department of Infectious Diseases investigated the role of microtubules in Plasmodium. Microtubules form an important part of the skeleton of most eukaryotic cells and are essential for many cellular functions such as cell division. They are also the targets for drugs against cancers and worms. Microtubules in cells from multicellular eukaryotes are usually highly dynamic: they constantly grow and shrink and there are so many microtubules in a cell that it is very difficult to count them.

In Plasmodium, however, microtubules are organized differently: When the parasites are formed in the mosquito they each have 16 microtubules that each are about 6 micrometer long. Using molecular genetic engineering, light and electron microscopy the Frischknecht laboratory could for the first time generate mutants that show different numbers of microtubules, ranging from the standard 16 down to 5. The researchers then investigated which of these mutants were able to form infected parasites and found that at least 10 microtubules are needed. Different mutants can also show different microtubule lengths, but if one changes only the expression level of the protein alpha1-tubulin, then only the microtubule number and not the length is changed. In order to explain this striking effect, the researchers developed a mathematical model for the nucleation and growth of microtubules in Plasmodium, in collaboration with the group of Ulrich Schwarz from the Institute for Theoretical Physics, with whom Friedrich Frischknecht collaborates in the framework of CellNetworks and also in the framework of CRC 1129 on integrative analysis of pathogen replication and spread.

This study showed for the first time that an important biological effect depends on the exact number of microtubules in a cell and will certainly inspire more studies on the role of microtubule numbers and lengths in different organisms.

Original publication: Microtubule number and length determine cellular shape and function in Plasmodium. The EMBO Journal. doi: 201915252/embj.2018100984

 

The short talk was presented at the CellNetworks symposium in April 2017 celebrating 10 years of the European Research Council, which partly funded the work in the Frischknecht lab.

 

 

Contact

Prof. Dr. Friedrich Frischknecht

Parasitology Unit

 Zentrum für Infektionskrankheiten Universitätsklinikum Heidelberg

Tеl: 06221 56-6537

E-Mail: freddy.frischknecht [ aT ] med.uni-heidelberg.de