Ruprecht-Karls-Universität Heidelberg
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Lanzer0118 - Scientist (f/m) / PhD position
Project no:
Lanzer0118

Project leader:

Project supervisor:
Lanzer, Michael
Application deadline:
30. Sep 2018
Start of PhD project:
1. Nov 2018

Project description:

Title:
Protection of malaria by haemoglobin S and C: A quantitative understanding of the cytoadhesion behavior
Summary:
Sickle cell haemoglobin (HbS) and the related haemoglobin C (HbC) bestow a survival benefit in infections with Plasmodium falciparum, the protozoan parasite causing the most virulent form of malaria in humans. The mechanism by which these structural haemoglobinopathies exert their protective function are only partly understood. Recent developments have pointed towards reduced cytoadhesion of parasitized erythrocytes to the microvascular endothelium as an underlying principle. Initial data suggest that reduced cytoadhesion is associated with altered membrane mechanics and a reduced deformability of the P. falciparum-infected erythrocyte. The project aims at providing a quantitative understanding of the membrane mechanics and how the membrane mechanics affects rheological and adhesive cell properties. To address this topic, the global cell elasticity of infected erythrocytes will be investigated, using a high-speed robotic pump device. The project further focuses on investigating the cytoadhesion footprint that the various infected erythrocytes leave on microvascular endothelial cells in flow, using label-free microinterferometry and optical force sensors. The findings will be subsequently integrated into mathematical models.

The salary will be according to TVL E13 65 % including social benefits, which will amount to a gross pay of approximately 30,000 € per year.
References:
1. Dasanna AK, Lansche C, Lanzer M, Schwarz US (2017) Rolling adhesion of schizont stage malaria-infected red blood cells in shear flow. Biophys J. 112:1908-1919.

2. Cyrklaff M, Srismith S, Nyboer B, Burda K, Hoffmann A, Lasitschka F, Adjalley S, Bisseye C, Simpore J, Mueller AK, Sanchez CP, Frischknecht F, Lanzer M (2016) Oxidative insult can induce malaria-protective trait of sickle and fetal erythrocytes. Nat Commun. 7:13401.

3. Helms G, Dasanna AK, Schwarz US, Lanzer M (2016) Modeling cytoadhesion of Plasmodium falciparum-infected erythrocytes and leukocytes-common principles and distinctive features. FEBS Lett. 590:1955-71.

4. 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 334:1283-6.
Methods that will be used:
P. falciparum cell culture, biophysical techniques, hydrodynamics, mathematical modeling, optical force sensors, quantitative reflection interference contrast microscopy (RICM), endothelial cell culture, endothelial cell activation assays
Cooperation partners:
This is a joint project with Prof. Ulrich Schwarz from the Department of Theoretical Physics and Prof. Motomu Tanaka from the Institute of Physical Chemistry.
Personal qualifications:
Qualified candidate should have a degree from an internationally accredited institution of higher education. Technical skills in biophysics and, preferentially in cell biology, are desirable. Interest in interdisciplinary collaborations is highly desirable. Applications from all fields of natural sciences and medicine are welcome.
Keywords:
Plasmodium; malaria; biomechanics, biophysics, sickle cell haemoglobin