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Cryo-ET of Alphavirus Replication Complex (CryoARC)

Project description

Research explores alphavirus mechanisms to tackle tropical diseases

Alphaviruses, including the Semliki Forest virus and the Chikungunya virus, pose significant health challenges to tropical regions owing to their mosquito-borne nature that causes widespread disease. These viruses replicate in specialised structures called spherules, which are not yet fully understood. Funded by the Marie Skłodowska-Curie Actions programme, the CryoARC project will seek to further explore these spherules by employing advanced techniques like cryo-electron tomography, proteomics, and bioinformatics. Researchers aim to uncover the 3D architecture of these viral complexes and their interactions with host proteins. CryoARC hopes to pave the way for innovative therapies against alphaviruses and support the growth of an independent research lab in Europe.

Objective

Positive-sense single-stranded RNA (+ssRNA) viruses replicate their genomes in membrane-bound, virus-induced replication complexes (RCs). A major genus of +ssRNA viruses are the Alphaviruses (family Togaviridae). Alphaviruses contain several mosquito-borne viruses that cause substantial human disease burden in tropical and subtropical regions, e.g. Semliki Forest Virus (SFV) and Chikungunya Virus (CHIKV). Alphavirus RCs (also referred to as “spherules”) are outward-facing, balloon-shaped plasma membrane buds of 50-80nm diameter. Our structural understanding of spherules is still fragmental and there is no complete 3D macromolecular architecture of these megadalton complexes. The proposed CryoARC project is based on extensive cryo-electron tomography (cryo-ET), proteomics and structural bioinformatics approaches to explore and resolve the in situ 3D structure of SFV spherule's complete neck-complex and identifying the host co-factors interacting with viral proteins. To accomplish the main goal of the CryoARC project, I will address the following objectives (1) Fractionation and purification of active SFV spherules from the infected mammalian cells for proteomics and structural studies, (2): In situ cryo-ET structure determination of the SFV spherule’s complete neck complex, and (3) Macromolecular interaction between viral and host-factors in the RC, and design potential antiviral drugs using computational approaches. The result of the CryoARC project will provide a novel fundamental insight into alphavirus replication, thus aiding development of future therapies for emerging medically and economically important Alphaviruses. The CryoARC project is further designed to allow me to utilize and share my own expertise in virology and protein structural biology, and to benefit from the inspiring and well-equipped host research laboratory. Acquired scientific and management skills will help me on the path towards establishing an independent research lab in Europe.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

UMEA UNIVERSITET
Net EU contribution
€ 222 727,68
Address
UNIVERSITETOMRADET
901 87 UMEA
Sweden
Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data