RESEARCH INTERESTS

RNA viruses are a diverse group of serious pathogens. Broadening structural insight into their molecular repertoire, and particularly virus-host intracellular interactions, is critical for a complete understanding of infection mechanisms. Host translation is one of the major sites of the virus-host battlefront. Being a center of cellular stress response pathways, it is often abused by viruses to produce viral proteins. Importantly, while the host translation gets switched off during infection, the viral one persists relying on the non-canonical translation strategies. Of particular interest is the fate of cytoplasmic RNA granules, since these compartments serve as a depository of host mRNA, stalled translation initiation complexes, and auxiliary factors that viruses can rely on during infection.

My lab will combine structural biology expertise (cryo-EM, cryo-ET, and X-ray crystallography) with an in vivo platform – mammalian cell cultures transfected with minimal replicon systems, mimicking viral transcription and replication inside the infected cell. We will use this platform as a test tube for various assays, including whole genome CRISPR-Cas9 screens to identify novel host factors involved in viral infection, functional and localization studies, as well as structural analysis. Knowledge acquired on the way will open new research avenues that may ultimately lead to the design of innovative therapies and broad-spectrum antivirals.

 

MEMBERS OF THE GROUP

Country
Name
Surname
Science Degree
Email
Eliana
Dukhno
e.dukhno@imol.institute
Moh Egy Rahman
Firdaus
f.rahman@imol.institute
Piotr
Gerlach
PhD
p.gerlach@imol.institute
 

PUBLICATIONS

2022

  • Gerlach P, Garland P, Lingaraju M, Salerno-Kochan M, Bonneau F, Basquin J, Jensen TH & Conti E. Structure and regulation of the Nuclear Exosome Targeting Complex guides RNA substrates to the exosome. Mol Cell (2022) in press

 

2020

  • Arragain B, Effantin G, Gerlach P, Reguera J, Schoehn G, Cusack S & Malet H. Pre-initiation and elongation structures of full-length La Crosse virus polymerase reveal functionally important conformational changes. Nat Commun (2020) 11: 3590, doi.org/10.1038/s41467-020-17349-4

  • Lingaraju M, Schuller JM, Falk S, Gerlach P, Bonneau F, Basquin J, Benda C & Conti E (2020) To Process or to Decay: A Mechanistic View of the Nuclear RNA Exosome. Cold Spring Harb Symp Quant Biol (2019) 84: 155-163, doi.org/10.1101/sqb.2019.84.040295
     

2018

  • Gerlach P, Schuller JM, Bonneau F, Basquin J, Reichelt P, Falk S & Conti E. Distinct and evolutionary conserved structural features of the human nuclear exosome complex. eLife (2018) 7: e38686, doi.org/10.7554/eLife.38686.001

 

2016

  • Reguera J, Gerlach P, Rosenthal M, Gaudon S, Coscia F, Günther S & Cusack S. Comparative structural and functional analysis of bunyavirus and arenavirus cap-snatching endonucleases. PLoS Pathog (2016) 12: e1005636, doi.org/10.1371/journal.ppat.1005636

  • Reguera J, Gerlach P & Cusack S. Towards a structural understanding of RNA synthesis by negative strand RNA viral polymerases. Curr Opin Struct Biol (2016) 36: 75-84, doi.org/10.1016/j.sbi.2016.01.002

2015

  • Gerlach P, Malet H, Cusack S & Reguera J. Structural insights into bunyavirus replication and its regulation by the vRNA promoter. Cell (2015) 161: 1267–1279, doi.org/10.1016/j.cell.2015.05.006

 

ABOUT GROUP LEADER

SHORT BIO

Dr. Piotr Gerlach joined ReMedy IRAP at the International Institute of Molecular Mechanisms and Machines (IMol) in summer 2021. During his PhD in Dr. Stephen Cusack’s group at EMBL in Grenoble, he succeeded in determining the first atomic structure of a bunyaviral polymerase. Securing an EMBO Long Term Fellowship, he joined prof. Elena Conti’s lab at Max Planck Institute of Biochemistry in Munich, where he studied the human RNA exosome using cryo-EM. Recently, dr. Gerlach has received an EMBO Installation Grant to set up his research team at IMol.

 

FUNDING

2022 - 2024

  • PASIFIC Grant (BunyaOut 46743)
     

2021 - 2025

  • EMBO Installation Grant (IG 4742)

 

2016 - 2018

  • EMBO Long - Term Fellowship (ALTF 1008-2015)

2011 - 2015

  • EMBL International PhD Programme Fellowship

2010 - 2011

  • FNP TEAM Master Studies Scholarship

2010

  • Erasmus Student Exchange Fellowship 2010