Ruprecht-Karls-Universität Heidelberg
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Guizetti_Frischknecht0119 - Scientist (f/m) / PhD position
Project no:
Guizetti_Frischknecht0119

Project leader:

Project supervisor:
Guizetti, Julien
Application deadline:
31. Jan 2020
Start of PhD project:
1. Mar 2020

Project description:

Title:
Understanding atypical cell division mechanisms in malaria parasites
Summary:
Plasmodium falciparum causes the most severe form of malaria still killing almost half a million children every year. Pathogenesis is linked to asexual proliferation in red blood cells and severity of malaria infection is predicted by parasite load. Even though cell division is fundamental to the rapid proliferation of this eukaryotic pathogen it is poorly studied and thus presents an exciting new avenue for research. P. falciparum displays significant morphological differences when compared to any model organism suggesting that atypical cell division mechanisms are in place. Our recent studies suggest that the key regulators of division, the centrosomes, have a significantly different structure and composition. Nuclear microtubules emerging from those centrosomes undergo dynamic changes that still have to be understood. Further, the coordination of key cell cycle events like DNA replication and chromosome segregation are unusual. By combining recent advances in live cell imaging, super-resolution microscopy, and genome-editing technologies you will aim to uncover these events are coordinated.

Opportunities:
If you are passionate about cell division biology and imaging approaches this PhD project will give you the opportunity to work on a neglected tropical pathogen that is still affecting millions of humans. You can expect a close supervision aiming towards a deep understanding of all connected scientific issues, developing appropriate scientific methods and communication skills, and becoming an independent researcher. If you are motivated to explore a novel field of research using cutting-edge technologies in a small group I would be happy to meet you for a personal discussion.
References:
Mehnert, A.K., Simon C.S., Guizetti, J.* (2019). Immunofluorescence staining protocol for STED nanoscopy of Plasmodium-infected red blood cells. Mol Biochem Parasitol. 229, 47-52.

Bryant J.M., Regnault C., Scheidig-Benatar C., Baumgarten S., Guizetti J.*, Scherf A. (2017). CRISPR/Cas9 Genome Editing Reveals That the Intron Is Not Essential for var2csa Gene Activation or Silencing in Plasmodium falciparum. MBio 8(4). pii: e00729-17.

Francia, M. E., & Striepen, B. (2014). Cell division in apicomplexan parasites. Nat Rev Microbiol, 12(2), 125–136.

Guizetti, J., Martins, R. M., Guadagnini, S., Claes, A., & Scherf, A. (2013). Nuclear pores and perinuclear expression sites of var and ribosomal DNA genes correspond to physically distinct regions in Plasmodium falciparum. Eukaryot Cell 12, 697-702.

J. Guizetti, L. Schermelleh, J. Mäntler, S. Maar, I. Poser, H. Leonhardt, T. Müller-Reichert, D. W. G. (2011). Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments. Science, 331(6024), 1616–1620.

Methods that will be used:
Parasite cell culture, molecular cloning, CRISPR/Cas9 genome-editing, advanced microscopy techniques such as live cell imaging, super-resolution, correlative light and electron microscopy, and more. Some images & movies can be found: www.guizettilab.com
Cooperation partners:
Dr. Markus Ganter, Department of Infectious Diseases, Parasitology
Prof. Dr. Freddy Frischknecht, Department of Infectious Diseases, Parasitology

Personal qualifications:
I expect a very good command of English with the ability to read, understand, and critically evaluate scientific literature; High motivation and dedication for doing science, more specifically cell biology and parasitology; Good laboratory, analytical and communication skills; and most importantly the ability and willingness to learn every day.
Keywords:
Parasite, Malaria, Cell division, Mitosis, CRISPR/Cas9 genome-editing, Super-resolution microscopy, electron microscopy