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Murray, K. A.

Publications and source records attributed to Murray, K. A..

4 recordsLinked to original sources

Inhibition of amyloid formation of the Nucleoprotein of SARS-CoV-2

The SARS-CoV-2 Nucleoprotein (NCAP) functions in RNA packaging during viral replication and assembly. Computational analysis of its amino acid sequence reveals a central low-complexity domain (LCD) having sequence features akin to LCDs in other proteins known to function in liquid-liquid phase separation. Here we show that in the presence of viral RNA, NCAP, and also its LCD segment alone, form amyloid-like fibrils when undergoing liquid-liquid phase separation. Within the LCD we identified three 6-residue segments that drive amyloid fibril formation. We determined atomic structures for fibrils formed by each of the three identified segments. These structures informed our design of peptide inhibitors of NCAP fibril formation and liquid-liquid phase separation, suggesting a therapeutic route for Covid-19. One Sentence SummaryAtomic structures of amyloid-driving peptide segments from SARS-CoV-2 Nucleoprotein inform the development of Covid-19 therapeutics.

biochemistry

Competition in depleting resource environments shapes the thermal response of mosquito population fitness

The temperature-dependencies of life history traits are increasingly being used to predict how climatic warming will affect vector-borne disease dynamics, partially by affecting the abundance dynamics of the vector population. Such predictions generally arise from mathematical models that incorporate the temperature dependence of traits measured under laboratory conditions. These temperature-trait relationships are typically estimated from juvenile populations reared under optimal resource conditions, even though natural populations experience intermittent resource depletion. Using laboratory experiments on the mosquito Aedes aegypti, combined with a stage-structured population model, we show that resource depletion in the juvenile habitat can significantly depress the vectors maximal population growth rate (rm) across the entire temperature range, cause it to peak at a lower temperature, and narrow its thermal niche width. Our results provide compelling evidence for future studies to consider resource depletion when predicting the effects of global change on vector-borne disease transmission, disease vectors and other arthropods.

ecology

Poor protection of amphibian evolutionary history reveals opportunities for global protected areas

As habitat loss is a major driver of amphibian population declines, protected areas (PAs) can play a crucial role in amphibian conservation. Documenting how well the global PA network captures the evolutionary history of amphibians can inform conservation prioritisation and action. We conducted a phylogenetic gap analysis to assess the extent to which amphibian phylogenetic diversity (PD) is unprotected by the PA network and compared this to other terrestrial vertebrate groups. 78% of amphibian species and 64% of global amphibian PD remains unprotected, which is higher than corresponding figures for squamates, mammals and birds. Amongst amphibians, salamanders were the least well protected, with 78% of PD unprotected, compared with 64% for caecilians and 63% for frogs. We identify areas that offer the greatest opportunity to capture unprotected amphibian evolutionary history. We could capture an additional 29.4% of amphibian PD, representing 40 billion years of evolutionary history, by protecting an additional 1.9% of global amphibian distributions (1.74% of global land area) and increasing the restrictions in 0.6% of amphibian distributions to match the management objectives of PAs in IUCN categories I or II. Importantly, we found that the spatial distribution of unprotected PD was correlated across all groups, indicating that expanding the PA network to conserve amphibian PD can secure imperilled vertebrate diversity more generally.

evolutionary biology

The effect of resource limitation on the temperature dependence of mosquito population fitness

Laboratory-derived temperature dependencies of life history traits are increasingly being used to make mechanistic predictions for how climatic warming will affect vector-borne disease dynamics, partially by affecting abundance dynamics of the vector population. These temperature-trait relationships are typically estimated from populations reared on optimal resource supply, even though natural populations of vectors are expected to experience variation in resource supply, including intermittent resource limitation. Using laboratory experiments on the mosquito Aedes aegypti, a principal arbovirus vector, combined with stage-structured population modelling, we show that low-resource supply significantly depresses the vectors maximal population growth rate across the entire temperature range (22-32{degrees}C) and causes it to peak at a lower temperature than at high-resource supply. This effect is primarily driven by an increase in juvenile mortality and development time, combined with an exaggerated decrease in adult size with temperature at low-resource supply. Our study suggests that projections of vector abundance and disease transmission based on laboratory studies are likely to substantially underestimate how resource supply can modulate the temperature-dependency of population-level fitness through its influence on juvenile survival and development time. Our results provide compelling evidence for future studies to consider resource supply when predicting the effects of climate and habitat change on disease vectors and transmission.

ecology