Ruprecht-Karls-Universität Heidelberg
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Guizetti0117 - Scientist (f/m) / PhD position
Project no:
Guizetti0117

Project leader:

Project supervisor:
Guizetti, Julien
Application deadline:
20. Sep 2017
Start of PhD project:
1. Oct 2017

Project description:

Title:
'Divide' and conquer: Understanding atypical proliferation mechanisms in malaria parasite infection
Summary:
Plasmodium falciparum causes the most severe form of malaria still killing about 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 mitosis 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. By combining recent advances in live cell imaging, super-resolution microscopy, and genome-editing technologies we will aim to uncover those mechanisms.
Currently, it is unclear how chromosome replication and segregation are coordinated. Further, a lack of canonical cell division checkpoints has been suggested and lastly Plasmodial centrosomes contain specific centrins of unknown function. Hence, three main objectives of this PhD project are:
i) Analyze coordination of chromosome replication, attachment and segregation
ii) Quantify if lack of mitotic checkpoints causes frequent segregation errors
iii) Functionally investigate the peculiar dynamics of centrosomes.

If you are passionate about cell division 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 if you contact me at julien.guizetti@gmail.com so we can arrange a personal discussion.
References:
Francia, M. E., & Striepen, B. (2014). Cell division in apicomplexan parasites. Nat Rev Microbiol, 12(2), 125–136.

Guizetti, J., Barcons-Simon, A., & Scherf, A. (2016). Trans-acting GC-rich non-coding RNA at var expression site modulates gene counting in malaria parasite. Nucleic Acids Research, 44(20), 9710–9718.

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:
Beside state of the art CRISPR/Cas9 genome-editing, we will use advanced microscopy techniques such as live cell imaging, super-resolution and correlative light and electron microscopy. Preliminary images & movies can be found here: http://julienguizetti.wixsite.com/malaria-mitosis.
Cooperation partners:
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 proliferation, Malaria, Cell division, Mitosis, CRISPR/Cas9 genome-editing, Super-resolution microscopy, Correlative light and electron microscopy.