Přehled

Doctoral study program: Life Sciences (Faculty of Science, Masaryk University)

Supervisor: Pavel Plevka

Annotation

Endosome rupture is a critical yet underexplored aspect of cellular biology, with significant implications for understanding immune responses, infection mechanisms, and drug delivery. The controlled rupture of endosomes can lead to cargo release into the cytoplasm. Despite its importance, the precise molecular mechanisms governing endosome rupture remain poorly understood. The student will use cryo-electron microscopy and molecular biology tools to characterize the putative role of endosome disruption in endocytosis of native cargo, including transferrin (clathrin-coated pit-mediated endocytosis), Anti-β1-adrenergic receptor (fast endophilin-mediated endocytosis), and anti-CD44/anti-CD98 (clathrin-independent carrier / glycosylphosphatidylinositol-anchored protein-enriched early endocytic compartment mediated endocytosis). He/she will also use cells deficient in selected mechanisms enabling endocytosis and endosome remodeling to determine which cellular processes are responsible for endosome disruption.

Recommended literature

  • Key principles and methods for studying the endocytosis of biological and nanoparticle therapeutics. Rennick JJ, Johnston APR, Parton RG. Nat Nanotechnol. 2021 Mar;16(3):266-276. doi: 10.1038/s41565-021-00858-8. Epub 2021 Mar 12. PMID: 33712737
  • Experimental Perspectives on Direct Visualization of Endosomal Rupture. Day RA, Sletten EM. Chembiochem. 2021 Dec 2;22(23):3277-3282. doi: 10.1002/cbic.202100379. Epub 2021 Sep 23. PMID: 34519410
  • Endosomal escape: A bottleneck for LNP-mediated therapeutics. Chatterjee S, Kon E, Sharma P, Peer D. Proc Natl Acad Sci U S A. 2024 Mar 12;121(11):e2307800120. doi: 10.1073/pnas.2307800120. Epub 2024 Mar 4. PMID: 38437552
  • Mechanisms of endocytosis. Doherty GJ, McMahon HT. Annu Rev Biochem. 2009;78:857-902. doi: 10.1146/annurev.biochem.78.081307.110540. PMID: 19317650

Research area: Structural biology, cell biology

Keywords: cryo-EM, cryo-ET, cargo, delivery, cell entry, endocytosis, endosome, membrane, rupture

Funding of the PhD candidate: The student will be supported by New technologies for translational research in pharmaceutical sciences /NETPHARM (CZ.02.01.01/00/22_008/0004607).

Requirements for candidate

The prospective student should be interested in learning cryo-EM and structure determination approaches. Previous experience with molecular biology, programming, scripting, and data analyses is a plus.

Information about the supervisor

Pavel Plevka is the Research Group Leader and Director of CEITEC Masaryk University in Brno, Czech Republic. Pavel Plevka has determined the structures of several viruses, most notably that of human enterovirus 71 that causes potentially fatal encephalitis in small children. Furthermore, he studied the maturation of the dengue virus. He focuses on cryo-electron microscopy of viruses and other macromolecular complexes. Pavel Plevka studied Molecular Biology and Virology at the Faculty of Science at Charles University in Prague and graduated in 2002, then went on to complete his doctoral studies in Structural Biology in 2009 at Uppsala University in Sweden. For the next four years, he worked as a Postdoctoral Research Associate in Michael Rossmann’s Group at Purdue University in the United States. In 2013, he received an ERC Starting Grant and established his own research group that is focused on Structural Virology at CEITEC Masaryk University in Brno. He is a laureate of the Neuron Prize for Young Scientists and the Werner von Siemens Prize for the most important discovery in basic research. In 2023, he became the Director of CEITEC Masaryk University. In 2022, he was awarded the ERC Consolidator Grant.

Information about the application process: https://www.ceitec.eu/ls-mm-phd/

Application webpage: https://www.ceitec.eu/endosome-rupture-in-delivery-of-native-cargo/t11449

Související pozice