Biology subjects

Wallace, S.

Publications and source records attributed to Wallace, S..

5 recordsLinked to original sources

bioRxiv2026

Near real-time data on the human neutralizing antibody landscape to influenza virus in summer of 2026 shows antigenic advance of H3N2 subclade K region D mutants and H1N1 D.3.1.1 Sa mutants

Human seasonal influenza evolves rapidly, necessitating twice yearly decisions about whether to update the strains in the vaccine. To help inform this decision, we have been using high-throughput sequencing-based neutralization assays to make twice yearly measurements of how recent human sera neutralize current human H3N2 and H1N1 strains. Here we provide the third installment in this series of measurements by reporting 52,268 titers representing neutralization of 148 viral strains by 355 human sera collected between April and August of 2026. Our measurements show that new H3N2 subclade K strains with mutations in antigenic region D and new H1N1 subclade D.3.1.1 strains with mutations in antigenic region Sa (such as G155E) have reduced neutralization by human sera, with notable heterogeneity in the impact of some of these mutations across sera from different individuals. This paper is accompanied by an interactive summary (https://jbloomlab.github.io/flu-seqneut-2026/summary.html) that enables detailed exploration of the results, and all titer data are publicly available for further analysis to aid vaccine antigen selection and studies of viral evolution.

microbiology↗

bioRxiv2026

Heterologous Rieske non-heme iron monooxygenases enable efficient microbial conversion of lignin guaiacol to adipic acid

Adipic acid (1,6-hexanedioic acid) is a key building block for nylon-6,6, a widely used polymer in the global chemical industry. Current industrial production relies on petrochemical feedstocks and nitric acid oxidation of cyclohexane/cyclohexanol mixtures, releasing nitrous oxide, a potent greenhouse gas. Biotechnological routes offer sustainable alternatives but have been limited by low yields or reliance on multi-strain systems. Here we report a one-pot, single-strain microbial process for the efficient conversion of guaiacol - a lignin derived aromatic - into adipic acid. By integrating heterologous Rieske non-heme iron monooxygenases from Cupriavidus necator N-1 with systematic process optimisations in engineered Escherichia coli, we achieve near-quantitative conversion with 97% yield and titres of 1.5 g/L in aqueous, lab-scale reactions. This work demonstrates a novel and efficient strategy for lignin valorisation through engineered microbial synthesis, providing a new sustainable and scalable route to adipic acid.

synthetic biology↗

bioRxiv2025

AtuR and MarR transcriptional repressors that sense fatty or naphthenic acids and regulate degradation or antimicrobial resistance operons in Pseudomonas sp. OST1909.

Naphthenic acids (NA) are a complex family of acyclic and cyclic carboxylic acids that accumulate in tailings after bitumen extraction from oil sands in Alberta. In response to exposure to naphthenic acids, Pseudomonas sp. OST1909 induces the expression of operons regulated by TetR and MarR-type transcriptional repressors. This class of repressor releases from promoters after binding small molecules, leading to a de-repression of the target operons. We propose that these regulators sense fatty and naphthenic acids and control the expression of genes required to cope with their exposure. Plasmid-encoded transcriptional lux reporters to the atu degradation and mar antimicrobial resistance promoters were constructed that also included the corresponding repressor protein, controlled by various strength constitutive promoters. We provide evidence that the atuAR and marR promoters are directly repressed by AtuR and MarR, respectively. His-tagged MarR and AtuR proteins bound to their promoters containing palindromic binding sites in electrophoretic mobility shift assays (EMSA). Fatty and naphthenic acid compounds and mixtures prevented promoter DNA binding to the repressor proteins in EMSA assays, which suggested direct analyte binding to the protein. The marR-H biosensor construct was functional when introduced into E. coli, confirming the role of NA sensing and transcriptional repressor proteins. This study provides mechanistic insight into the use of NA-inducible promoters as bacterial biosensors for NA detection and identifies novel ligands for the MarR and TetR types of repressor proteins. ImportanceUnderstanding the gene expression responses to environmental pollutants is necessary to construct whole cell biosensors that can be employed as a monitoring technology. We have previously identified bacterial genes that were induced by exposure to naphthenic acids, a complex family of cyclic and polycyclic, alkyl substituted carboxylic acids that originate in oil sands but accumulate in the water used to extract bitumen from oil sands. In this study we focus on MarR and TetR-type regulatory proteins and their role in binding fatty acids and naphthenic acids, to further our understanding of how bacteria sense these compounds and mitigate a gene expression response.

microbiology↗

bioRxiv2022

Overproduction of Native and Click-able Colanic Acid Slime from Engineered Escherichia coli

The fundamental biology and application of bacterial exopolysaccharides is gaining increasing attention. However, current synthetic biology efforts to produce the major component of Escherichia sp. slime, colanic acid, and functional derivatives thereof have been limited. Herein, we report the overproduction of colanic acid (up to 1.32 g/L) from D-glucose in an engineered strain of E. coli JM109. Furthermore, we report that chemically-synthesized L-fucose analogues containing an azide motif can be metabolically incorporated into the slime layer via a heterologous fucose salvage pathway from Bacteroides sp. and used in a click reaction to attach an organic cargo to the cell surface. This molecular engineered bio-polymer possesses enormous potential as a new tool for use in chemical, biological and materials research.

bioengineering↗

bioRxiv2021

One dose of COVID-19 nanoparticle vaccine REVC-128 provides protection against SARS-CoV-2 challenge at two weeks post immunization

A COVID-19 vaccine with capability to induce early protection is needed to efficiently eliminate viral spread. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomain subunits with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titer at two weeks post immunization, which is significantly higher than titer induced by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for SARS-CoV-2 virus challenge was implemented at two weeks post a single dose of REVC-128 immunization. The results show that vaccination protects hamsters against SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage (lung and nares) for protected animals, compared with ~10% weight loss, higher viral loads and tissue damage in unprotected animals. Furthermore, the data show that vaccine REVC-128 is thermostable at up to 37{degrees}C for at least 4 weeks. These findings, along with a long history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine candidate to induce the earliest protection against SARS-CoV-2 infection.

microbiology↗