E7 P: Neglected infectious diseases with focus on imaging
Prof. Dr. Jacomina Krijnse Locker
Elektronenmikroskopie von Pathogenen
Paul-Ehrlich-Institut
Paul-Ehrlich-Straße 51-59
63225 Langen
Tel.: +49 (0)6103-77 2011
E-Mail: Jacomina.KrijnseLocker(at)pei(dot)de
Project description:
We apply imaging techniques to understand how pathogens interact with cells to cause disease, focusing on electron microscopy (EM) and correlated light- and electron microscopy (CLEM). To generate robust protocols that can easily be adapted, we use our model virus, the large DNA-virus vaccinia (VACV).
The SARS CoV2 pandemic illustrates how viruses have a world-wide socio-economical impact with dramatic consequences for the neglected tropical diseases (NTDs). There is an urgent need to contain the SARS CoV2 pandemic and refocus resources on NTDs. In a collaborative effort we showed that the spike-surface protein (S) of SARS COV2, that mediates infection, shows unexpected flexibility. The latter could facilitate receptor binding and cell entry of the virus, which remains to demonstrated.
Cryo-electron tomography and molecular dynamic simulation of SARS-CoV-2 spike shows unexpected flexibility of the stalk.
Upon budding at intracellular membranes coronaviruses leave the cell in a poorly explored way. Vesicular trafficking as well as regulated lysosomal exocytosis have been proposed.
Scientific goal:
The project aims to interfere with the flexibility of S and test for the outcome of infection using antibodies, drugs and genetics. Virus release from infected cells will be studied by a CLEM approach, combining live cell imaging with EM. The expertise gained from our VACV- and SARS CoV2 host system is then applied to answer questions related to virus-host systems used in other teams of the DRUID-consortium.
DRUID Collaboration partners:
A3 Weber lab, B2 Ziebuhr lab, B6 P Herker lab, C1 Hildt lab, D3 van Zandbergen lab, E5 Czermak lab
References E7 P: Turoňová, B., et al. (2020). Science (80-. ). 370, 203–208. Blanco-Rodriguez, G., et al. (2020). J. Virol. 94 e00135-20. Quemin, E.R., et al. (2018). J. Mol. Biol.430, 1714-1724. Chlanda, P., and Krijnse Locker, J. (2017). Biochem. J. 474, 1041–1053. Sartori-Rupp, A., et al. (2019). Nat. Commun. 10, 342.