Přehled

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

Supervisor
Pavel Plevka

Annotation

To initiate infection, viruses deliver their genomes into host cells. Whereas enveloped viruses fuse their membrane with that of a cell, the cell entry mechanisms employed by non-enveloped viruses are less understood. Recently, it has been shown that endosome rupture enables cell entry of picornaviruses. The student will analyze the putative role of endosome rupture in the cell entry of adenoviruses, polyomaviruses, and parvoviruses. He/She will employ cryo-electron microscopy and tomography to visualize the early stages of cell virus entry in peripheral parts of cells that can be imaged using transmission electron microscopy. The student will analyze changes in the structure of virus particles and endosome membranes that enable the viruses to deliver their genomes into the cytoplasm.

Recommended literature
Virus entry by endocytosis. Mercer J, Schelhaas M, Helenius A. Annu Rev Biochem. 2010;79:803-33. doi: 10.1146/annurev-biochem-060208-104626. PMID: 20196649
Adenovirus Entry: From Infection to Immunity. Greber UF, Flatt JW. Annu Rev Virol. 2019 Sep 29;6(1):177-197. doi: 10.1146/annurev-virology-092818-015550. Epub 2019 Jul 5. PMID: 31283442
Sending mixed signals: polyomavirus entry and trafficking. Mayberry CL, Bond AC, Wilczek MP, Mehmood K, Maginnis MS. Curr Opin Virol. 2021 Apr;47:95-105. doi: 10.1016/j.coviro.2021.02.004. Epub 2021 Mar 6. PMID: 33690104
Parvoviral host range and cell entry mechanisms. Cotmore SF, Tattersall P. Adv Virus Res. 2007;70:183-232. doi: 10.1016/S0065-3527(07)70005-2. PMID: 17765706
Research area
Structural biology, virology

Keywords
virus, structure, cryo-EM, genome, delivery, cell entry, endocytosis, endosome, membrane, rupture

Funding of the PhD candidate
The student will be supported by the National Institute of Virology and Bacteriology (LX22NPO5103).

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-escape-of-non-enveloped-viruses/t11448