Biology subjects

Grey, E.

Publications and source records attributed to Grey, E..

4 recordsLinked to original sources

bioRxiv2025

De novo design of protein nanoparticles with integrated functional motifs

Computational design of self-assembling proteins has long relied on pre-existing structures and sequences, fundamentally limiting control over their structural and functional properties. Recent machine learning-based methods have transformed our ability to design functional small de novo proteins and oligomers, yet methods to design large de novo protein assemblies with structures tailored to specific applications are still underexplored. Here, we develop a generalizable method for designing de novo symmetric protein complexes that incorporate target functional motifs into their structures. We report 34 new protein nanoparticles that form on-target assemblies with cubic point group symmetries. The nanoparticles exhibit a wide variety of backbones that were designed with atom-level accuracy, as evidenced by several cryo-EM and crystal structures that reveal minimal deviations from the design models. We use the method to generate a de novo antigen-tailored nanoparticle vaccine that elicits robust immune responses in mice. These results establish a generalizable approach that can be used to design functional self-assembling protein complexes with structures tailored to specific applications.

biochemistry↗

bioRxiv2025

Stabilization of H5 highly pathogenic avian influenza hemagglutinin improves vaccine-elicited neutralizing antibody responses

Transmission of highly pathogenic avian influenza from H5 clade 2.3.4.4b has expanded in recent years to infect large populations of birds and mammals, heightening the risk of a human pandemic. Influenza viruses adapted to transmission in birds and some other animals tend to have a less stable hemagglutinin (HA) than seasonal influenza viruses, enabling membrane fusion at comparatively high pH levels. Here, we combine five mutations within H5 HA that dramatically increase its melting temperature and promote stable closure of the HA trimer. Structural analysis by cryo-electron microscopy revealed that the stabilizing mutations create several new hydrophobic interactions, while maintaining local HA structure. We found that vaccinating mice with stabilized H5 HA immunogens resulted in higher hemagglutination inhibition and neutralization titers than non-stabilized comparators. Epitope mapping of vaccine-elicited polyclonal antibody responses using negative stain electron microscopy and deep mutational scanning showed that site E on the side of the HA receptor binding domain was immunodominant across all groups; however, the stabilized immunogens shifted responses toward the receptor binding site (RBS), eliciting a higher proportion of neutralizing antibodies. These findings highlight that H5 HA-stabilizing mutations enhance the quality of antibody responses across different vaccine formats, underscoring their potential to improve pandemic preparedness vaccines targeting viruses from this widely circulating clade. One Sentence SummaryVaccinating with stabilized H5 HA increases the proportion of humoral responses against neutralizing RBS epitopes.

immunology↗

bioRxiv2021

Global port survey quantifies commercial shippings effect on biodiversity

Spread of nonindigenous organisms by shipping is one of the largest threats to coastal ecosystems. Limited monitoring and understanding of this phenomenon currently hinder development of effective prevention policies. Surveying ports in North America, South America, Europe, Southeast Asia, and Australia we explored environmental DNA community profiles evident of ship-born species spread. We found that community similarities between ports increased with the number of ship voyages, particularly if the ports had similar environments, and when indirect stepping-stone connections were considered. We also found 57 known non-indigenous taxa, some in hitherto unreported locations. We demonstrate the usefulness of eDNA-based tools for global biodiversity surveys, and highlight that shipping homogenizes biodiversity in predictable that could inform policy and management.

ecology↗

bioRxiv2019

Higher-order patterns of aquatic species spread through the global shipping network

The introduction and establishment of non-indigenous species (NIS) through global ship movements is a significant threat to marine ecosystems and economies. While ballast-vectored invasions have been partly addressed by some national policies and an international agreement regulating the concentrations of organisms in ballast water, biofouling-vectored invasions remain a large risk. Development of additional realistic and cost-effective ship-borne NIS policies requires an accurate estimation of NIS spread risk from both ballast water and biofouling. In this paper, we demonstrate that first-order Markov assumptions limit accurate modeling of NIS spread risks through the global shipping network. In contrast, we show that higher-order patterns overcome this limitation by revealing indirect pathways of NIS transfer. We accomplish this by developing Species Flow Higher-Order Networks (SF-HON), which we developed independently for ballast and biofouling, for comparison with first-order Markovian models of ballast and biofouling. We evaluated SF-HON predictions using the largest available datasets of invasive species for Europe and the United States. We show that not only does SF-HON yield more accurate NIS spread risk predictions than first-order models and existing higher-order models, but also that there are important differences in NIS spread via the ballast and biofouling vectors. Our work provides information that policymakers can use to develop more efficient and targeted prevention strategies for ship-borne NIS spread management, especially as management of biofouling is of increasing concern.

ecology↗