Huber RG

Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells

Dengue (DENV) and Zika (ZIKV) viruses are important human pathogens belonging to the Flaviviridae family of RNA viruses. DENV is known to infect around 390 million people around the world annually [1], while ZIKV causes numerous diseases including microcephaly in infants [2]. Currently, limited treatments and vaccines are available and novel strategies and targets are urgently needed to develop therapeutics to treat these diseases. To achieve this, it is important to understand host factors and how they interact with DENV and ZIKV genomes during the viral life cycle.

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Flavivirus genome recoding by codon optimisation confers genetically stable in vivo attenuation in both mice and mosquitoes

The mosquito-borne flaviviruses such as dengue virus (DENV) and Zika virus (ZIKV) have established themselves as major human pathogens. Live attenuated vaccines are seen as the most effective method for preventing flavivirus infection. Flavivirus genome recoding has emerged as a next-generation vaccine development method that acts by rewriting the flavivirus genome. Previous flavivirus genome recoding attempts were based on deoptimising the flavivirus genome. However, these deoptimised flaviviruses were found to be attenuated in a species dependent manner. For example, deoptimised DENV and ZIKV did not demonstrate attenuation in mosquito cells or mosquito animal models, which is undesirable because these mosquito-borne flaviviruses should be attenuated in their mosquito vector to prevent vaccine escape. To overcome these limitations, we adopted a flavivirus genome recoding approach based on the contrary approach of optimising the flavivirus genome and applied it to DENV2 and ZIKV. We found that this genome recoding approach of codon optimisation could confer attenuation in both mouse and mosquito animal models. This indicates that our flavivirus genome recoding approach may be used as a reliable method to construct attenuated vaccine backbones for the mosquito-borne-flaviviruses in general.

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Whole Genomic Characterization of Streptococcus iniae Isolates from Barramundi (Lates calcarifer) and Preliminary Evidence of Cross-Protective Immunization

Lates calcarifer, also known as Barramundi or Asian seabass, is a highly productive and fast-growing species that is well suited to large-scale aquaculture due to its attractive harvestable yields (premium fish). This fish has been envisioned as having the potential to be the “Salmon of Tropics”. Cultivating Lates calcarifer in aquaculture poses challenges, as the dense populations that make such aquaculture commercially viable facilitate the rapid spread of infectious diseases, which in turn significantly impact yield

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Tracking and blocking interdependencies of cellular BRAF-MEK oncokinase activities

The selective targeting of mutated kinases in cancer therapies has the potential to improve therapeutic success and thereby the survival of patients. In the case of melanoma, the constitutively active MAPK pathway is targeted by a combinatorial inhibition of BRAF and MEK activities.

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Dengue Virus Capsid Protein Facilitates Genome Compaction and Packaging

Keywords: dengue; RNA structure; RNA–protein interactions; virus packaging

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Identification of potential pathways and biomarkers linked to progression in ALS

To identify potential diagnostic and prognostic biomarkers for clinical management and clinical trials in amyotrophic lateral sclerosis.

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Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions

SARS-CoV-2 is a major threat to global health. Here, we investigate the RNA structure and RNA-RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 in cells using Illumina and Nanopore platforms. We identify twelve potentially functional structural elements within the SARS-CoV-2 genome, observe that subgenomic RNAs can form different structures, and that WT and Δ382 virus genomes fold differently.

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The nanotube express: Delivering a stapled peptide to the cell surface

Hypothesis Carbon nanotubes (CNTs) represent a novel platform for cellular delivery of therapeutic peptides. Chemically-functionalized CNTs may enhance peptide uptake by improving their membrane targeting properties.

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