Deciphering the RBPome in mosquitoes during virus infection

Informazioni relative al progetto

DRmov

ID dell’accordo di sovvenzione: 842067

DOI

10.3030/842067

Progetto chiuso

Data della firma CE 20 Marzo 2019

Data di avvio 1 Gennaio 2020

Data di completamento 31 Dicembre 2021

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 224 933,76

Contributo UE

€ 224 933,76

Coordinato da

UNIVERSITY OF GLASGOW
United Kingdom

Periodic Reporting for period 1 - DRmov (Deciphering the RBPome in mosquitoes during virus infection)

Periodo di rendicontazione: 2020-01-01 al 2021-12-31

Sintesi del contesto e degli obiettivi generali del progetto

Humans have been in contact with emerging and re-emerging infectious diseases since hundreds of years, however recent indications suggest that the frequency and severity of such diseases are rapidly increasing. Considering that two third of such illness are caused by RNA viruses, such as dengue fever (DENV), severe pneumonia (SARS-Cov-2), and polyarthritis (CHIKV), investigating this group of pathogens is vital to predict and manage the severity of any incoming emerging viruses. Considering that the genetic material for these pathogenic viruses is RNA with limited coding capacity, host RNA binding proteins are hijacked to facilitate different viral processes including viral RNA transcription, translation and virions assembly. Here we focus on mosquito-borne diseases, which has expanded dramatically in the last few decades to become an emerging global health problem, with around 1 billion new infections and 1 million deaths each year. I propose a workflow composed of number of unbiased, cutting edge, high-throughput techniques with three main objectives 1) determining the RBPome of mosquito cells 2) identification of the complement of mosquito RBPs involved in virus infection 3) role of selected mosquito RBPs in viral infection.
Moreover, the overall objective of the proposed work is to create a workflow not relying on prior detailed knowledge about host-virus interactions, consequently it offers to be an unprecedented unbiased approach that is well-suited for investigating emerging virus infections

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

Identification of mosquito RBPome: Due to their ability to tolerate and spread significant number of virus infections, mosquitos are clinically and economically important organisms. During the course of the fellowship, I have identified first known mosquito RBPome, include central proteins of innate immunity and host-virus interactions, as well as hundreds of proteins previously unknown to bind RNA suggesting specialized gain of function in mosquitos.

Developing a viral RNA interactome capture: I have developed the viral RNA interactome capture, which is a widely applicable technique to identify proteins binding specifically to viral RNA. I applied this technique in both mosquitos and human cells with wide range of viruses including Sindbis and SARS-CoV2. The significance of identifying proteins binding to viral RNA can be summarized in two aspects 1) they reflect the proteins involved in processing viral RNA leading to better understanding of the virus life cycle 2) due to their direct interaction with viral RNA, they are highly likely to be essential for virus infection thus presenting numerous for therapeutic interventions (which I show in the presented publications as well)

Applying the DRmov workflow on newly emerging virus infections: At the time of writing the fellowship application at 2018, I presented DRmov as a standalone workflow composed of a number of consequential techniques to address lack of information about emerging viruses and poorly-studied vectors. With emergence of SARS-CoV2 and dominance of COVID19 in 2020, I applied the DRmov workflow to such threat. This work (which is award-winning and published in Molecular cell) presented details about SARS-CoV2 life cycle and provided several opportunities for therapeutic intervention.

results exploitation and dissemination

The work described here is covered by 2 research publications, one review, one protocol and two manuscripts in preparation
Published:
Kamel et al Molecular Cell 2021
Kamel et al BioRxiv 2021
Iselin, et al Trends Biochem. Sci. 2021

In preparation
Kamel et al (vRIC protocol, following invitation from STAR protocols), expected submission May2022
Kamel et al (Identification of mosquito RBPome), expected submission June 2022

Moreover, I have presented this work in the following conferences
1- Poster at “RNA UK 2020”, January 2020
2- Talk at “Oxford talks - Infection and Disease Processes Seminar Series” March 2020
3- Talk at “RNA Society conference” June 2021
4- Talk at “BSPR conference” July 2021
5- Talk at “London Proteomics” Sept 2021
6- scheduled talk at “Virology Symposium” May 2022


Additionally, I made/involved in YouTube videos describing my results to general public and specialized researchers

https://www.youtube.com/watch?v=SRnr9yfPPrY&t=3s
https://www.youtube.com/watch?v=bX7bi4fqLzY&t=461s

Also, I received the following award for my work:

Early Career Research Award, British Society for Proteome Research (BSPR)

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

Overall, I believe one of main challenge in the virology field is how to translate basic research into more applied findings. During my fellowship I attempted to address this challenge by assembling DRmov workflow with several successful outcomes. Due to the versatility of the workflow, it can be applied to other organisms such as bats, similar to mosquito, they are known to tolerate and spread significant number of highly pathogenic virus infections

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