Prof M L Lanzer
Applications accepted all year round
About the Project
Malaria is a severe and potentially deadly infectious disease caused by the protozoan parasite Plasmodium falciparum. However, not every infected person develops life-threatening symptoms. Some people are protected by naturally occurring genetic polymorphisms, such as those leading to the haemoglobinopathies HbS and HbC. There is evidence suggesting that HbS and HbC confer protection by reducing the cytoadhesiveness of parasitised erythrocytes. For effective cytoadhesion, the major adhesin molecule PfEMP1 needs to be placed in parasite-induced knob-like protrusions on the erythrocyte plasma membrane. Infected HbS and HbC erythrocytes, however, possess fewer and abnormally enlarged knobs and the amount of PfEMP1 molecules presented is reduced and aberrantly displayed. The object of this project is to determine the knob density and the knob geometry and the absolute number of adhesion proteins per knob on the surface of the various parasitized erythrocyte. The project will involve a broad range of techniques, including generation of transgenic P. falciparum lines using the CRISPR/CAS9 transfection system, super resolution microscopy and atomic force microscopy.
Methods that will be used:
Molecular cloning; cell culture; transfection of P. falciparum; super resolution microscopy (PALM); atomic force microscopy; computational methods; statistical methods.
Cooperation partners:
Ulrich Schwarz : Institute for Theoretical Physics, Heidelberg University
Keywords:
Malaria, cytoadhesion, PALM, super resolution microscopy, sickle cell haemoglobin, atomic force microscopy
How to apply:
Applications are to be submitted via the online system of the Hartmut Hoffmann-Berling International Graduate School Of Molecular And Cellular Biology (HBIGS), www.hbigs.uni-heidelberg.de
Application deadline: Open until position is filled.
Start of PhD project: As soon as possible.
Funding Notes
Qualified candidate should have a degree from an internationally accredited institution of higher education. Technical skills in molecular cloning, cell culture, super resolution microscopy, or atomic force microscopy are desirable. Applications from all fields of natural sciences including biology, physics, or biophysics are welcome
References
Rieger H, Yoshikawa HY, Quadt K, Nielsen MA, Sanchez CP, Salanti A, Tanaka M, Lanzer M (2015) Cytoadhesion of Plasmodium falciparum-infected erythrocytes to chondroitin-4-sulfate is cooperative and shear enhanced. Blood 125:383-391.
Kilian N, Dittmer M, Cyrklaff M, Ouermi D, Bisseye C, Simpore J, Frischknecht F, Sanchez CP, Lanzer M 2013. Haemoglobin S and C affect the motion of Maurer's clefts in Plasmodium falciparum-infected erythrocytes. Cell Microbiol. 15:1111-1126.
Cyrklaff M, Sanchez CP, Kilian N, Bisseye C, Simpore J, Frischknecht F, Lanzer M 2011. Hemoglobins S and C interfere with actin remodeling in Plasmodium falciparum-infected erythrocytes. Science, 334:1283-1286.
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