Dr. Sara Clohisey

Dr. Sara Clohisey

Post Doctoral Biologist at The Roslin Institute, University of Edinburgh.

Publications

Dynamic data-driven meta-analysis for prioritisation of host genes implicated in COVID-19.

Published in Scientific Reports, 2020

The increasing body of literature describing the role of host factors in COVID- 19 pathogenesis demonstrates the need to combine diverse, multi-omic data to evaluate and substantiate the most robust evidence and inform development of therapies. Here we present a dynamic ranking of host genes implicated in human betacoronavirus infection (SARS-CoV-2, SARS-CoV, MERS-CoV, seasonal coronaviruses). Researchers can search and review the ranked genes and the contribution of different experimental methods to gene rank here

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Genetic mechanisms of critical illness in Covid-19.

Published in Nature, 2020

The subset of patients who develop critical illness in Covid-19 have extensive inflammation affecting the lungs and are strikingly different from other patients: immunosuppressive therapy benefits critically-ill patients, but may harm some non-critical cases. Since susceptibility to life-threatening infections and immune-mediated diseases are both strongly heritable traits, we reasoned that host genetic variation may identify mechanistic targets for therapeutic development in Covid-19.

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Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection.

Published in Cell, 2020

This work was carried out by colleagues at the CVR and Icahn School of Medicine at Mount Sinai. We report the existence of this mechanism of gene origination, which we named “start-snatching.” Depending on the reading frame, start-snatching allows the translation of host and viral “untranslated regions” (UTRs) to create N-terminally extended viral proteins or entirely novel polypeptides by genetic overprinting.

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Comprehensive characterisation of molecular host-pathogen interactions in influenza-A virus infected human macrophages.

Published in Journal of Virology, 2020

We were able to quantify overrepresentation of host RNA features among the sequences that were ‘Cap-snatched’ by IAV. We demonstrate biased snatching of numerous host RNAs, particularly small nuclear RNAs (snRNAs), and avoidance of host transcripts encoding host ribosomal proteins, which are required by IAV for replication. We then used a systems approach to describe the transcriptional landscape of the host response to IAV, observing many new features. You can see a summary of the paper here along with a brief overview of the cap-snatching mechanism.

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Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection.

Published in Nature Communications, 2020

Host dependency factors that are required for influenza A virus infection may serve as therapeutic targets as the virus is less likely to bypass them under drug-mediated selection pressure. Previous attempts to identify host factors have produced largely divergent results, with few overlapping hits across different studies. Here, we perform a genome-wide CRISPR/Cas9 screen and devise a new approach, meta-analysis by information content (MAIC) to systematically combine our results with prior evidence for influenza host factors.

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Host susceptibility to severe influenza A virus infection.

Published in Critical Care, 2019

Wide variation in susceptibility is a general feature of human and animal populations exposed to any pathogen. Explaining the mechanisms of susceptibility may enable effective targeting of vaccine therapies, may reveal new therapeutic approaches, and, in theory, may contribute to future clinical risk prediction models. We explore this in our review.

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