Publications by authors named "Spencer C Knight"

Article Synopsis
  • COVID-19 and influenza are respiratory illnesses caused by different viruses but share some symptoms and clinical risk factors, yet their genetic connections remain poorly understood.
  • A study involving over 18,000 influenza cases and nearly 276,000 control subjects found no common genetic risk factors between COVID-19 and influenza, revealing specific gene variants linked only to influenza.
  • The research highlights the potential for targeting cell surface receptors involved in viral entry, showing that manipulating specific genes could lead to treatments that prevent both COVID-19 and influenza infections.
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Objectives: The enormous toll of the COVID-19 pandemic has heightened the urgency of collecting and analysing population-scale datasets in real time to monitor and better understand the evolving pandemic. The objectives of this study were to examine the relationship of risk factors to COVID-19 susceptibility and severity and to develop risk models to accurately predict COVID-19 outcomes using rapidly obtained self-reported data.

Design: A cross-sectional study.

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Multiple COVID-19 genome-wide association studies (GWASs) have identified reproducible genetic associations indicating that there is a genetic component to susceptibility and severity risk. To complement these studies, we collected deep coronavirus disease 2019 (COVID-19) phenotype data from a survey of 736,723 AncestryDNA research participants. With these data, we defined eight phenotypes related to COVID-19 outcomes: four phenotypes that align with previously studied COVID-19 definitions and four 'expanded' phenotypes that focus on susceptibility given exposure, mild clinical manifestations and an aggregate score of symptom severity.

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Article Synopsis
  • A genome-wide association study identified a genetic variant (rs190509934) that reduces ACE2 expression by 37% and lowers the risk of SARS-CoV-2 infection by 40%.
  • The study confirms six previously known genetic risk variants, with four linked to worse outcomes in COVID-19 infected individuals.
  • A risk score based on common variants was developed, which improves prediction of severe disease beyond just demographic and clinical factors.
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The discovery of the CRISPR-Cas9 endonuclease has enabled facile genome editing in living cells and organisms. Catalytically inactive Cas9 (dCas9) retains the ability to bind DNA in an RNA-guided fashion, and has additionally been explored as a tool for transcriptional modulation, epigenetic editing, and genome imaging. This Review highlights recent progress and challenges in the development of dCas9 for imaging genomic loci.

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Bacterial adaptive immune systems use CRISPRs (clustered regularly interspaced short palindromic repeats) and CRISPR-associated (Cas) proteins for RNA-guided nucleic acid cleavage. Although most prokaryotic adaptive immune systems generally target DNA substrates, type III and VI CRISPR systems direct interference complexes against single-stranded RNA substrates. In type VI systems, the single-subunit C2c2 protein functions as an RNA-guided RNA endonuclease (RNase).

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The RNA-guided CRISPR-associated protein Cas9 is used for genome editing, transcriptional modulation, and live-cell imaging. Cas9-guide RNA complexes recognize and cleave double-stranded DNA sequences on the basis of 20-nucleotide RNA-DNA complementarity, but the mechanism of target searching in mammalian cells is unknown. Here, we use single-particle tracking to visualize diffusion and chromatin binding of Cas9 in living cells.

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We report the results of a comprehensive investigation of the recently discovered stereoselective and controlled polymerization of racemic lactide (D,L-LA) using an initiator prepared in situ from indium(III) chloride (InCl(3)), benzyl alcohol (BnOH), and triethylamine (NEt(3)). Linear relationships between number-average molecular weight (M(n)) and both monomer to alcohol concentration ratio and monomer conversion are consistent with a well-controlled polymerization. Studies on polymerization kinetics show the process to be first-order in [InCl(3)](0) and zero-order in both [BnOH](0) and [NEt(3)](0).

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