Publications by authors named "Alexander N Baker"

In structural terms, the sialic acids are a large family of nine carbon sugars based around an alpha-keto acid core. They are widely spread in nature, where they are often found to be involved in molecular recognition processes, including in development, immunology, health and disease. The prominence of sialic acids in infection is a result of their exposure at the non-reducing terminus of glycans in diverse glycolipids and glycoproteins.

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Article Synopsis
  • * Traditional antibody assays struggle to differentiate between glycoforms, but a new 'sandwich' bioassay uses immobilized antibodies and gold nanoparticles with lectins to improve detection capabilities.
  • * This enhanced method can detect specific glycoforms at very low concentrations (as low as 0.04 μg/mL) without requiring sample enrichment or complex steps, demonstrating its potential in distinguishing cancerous from non-cancerous forms of prostate specific antigen.
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Ice binding proteins (IBP) have evolved to limit the growth of ice but also to promote ice formation by ice-nucleating proteins (INPs). IBPs, which modulate these seemingly distinct processes, often have high sequence similarities, and molecular size/assembly is hypothesized to be a crucial determinant. There are only a few synthetic materials that reproduce INP function, and rational design of ice nucleators has not been achieved due to outstanding questions about the mechanisms of ice binding.

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Article Synopsis
  • - Glycan-lectin interactions are critical in biological processes like pathogen attachment and immune response, but current methods to study these interactions are often expensive and not widely accessible.
  • - Recently developed glycosylated plasmonic nanoparticles offer a cost-effective biosensor alternative that detects glycan-protein binding through noticeable color changes, which can be analyzed with simple equipment.
  • - This research suggests optimal parameters (gold core size and polymer tether length) for using these nanoparticles, allowing lab users to efficiently investigate new glycan/protein interactions with minimal optimization needed.
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Current point-of-care lateral flow immunoassays, such as the home pregnancy test, rely on proteins as detection units ( antibodies) to sense for analytes. Glycans play a fundamental role in biological signalling and recognition events such as pathogen adhesion and hence they are promising future alternatives to antibody-based biosensing and diagnostics. Here we introduce the potential of glycans coupled to gold nanoparticles as recognition agents for lateral flow diagnostics.

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The COVID-19 pandemic has highlighted the need for innovative biosensing, diagnostic, and surveillance platforms. Here we report that glycosylated, polymer-stabilized, gold nanorods can bind the SARS-CoV-2 spike protein and show correlation to the presence of SARS-CoV-2 in primary COVID-19 clinical samples. Telechelic polymers were prepared by reversible addition-fragmentation chain-transfer polymerization, enabling the capture of 2,3-sialyllactose and immobilization onto gold nanorods.

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Lateral flow devices are rapid (and often low cost) point-of-care diagnostics-the classic example being the home pregnancy test. A test line (the stationary phase) is typically prepared by the physisorption of an antibody, which binds to analytes/antigens such as viruses, toxins, or hormones. However, there is no intrinsic requirement for the detection unit to be an antibody, and incorporating other ligand classes may bring new functionalities or detection capabilities.

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The onset of COVID-19, coupled with the finer lens placed on systemic racial disparities within our society, has resulted in increased discussions around mental health. Despite this, mental health struggles in research are still often viewed as individual weaknesses and not the result of a larger dysfunctional research culture. Mental health interventions in the science, technology, engineering, and mathematics (STEM) academic community often focus on what individuals can do to improve their mental health instead of focusing on improving the research environment.

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Lateral flow immuno-assays, such as the home pregnancy test, are rapid point-of-care diagnostics that use antibody-coated nanoparticles to bind antigens/analytes (e.g., viruses, toxins or hormones).

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The COVID-19 pandemic, and future pandemics, require diagnostic tools to track disease spread and guide the isolation of (a)symptomatic individuals. Lateral-flow diagnostics (LFDs) are rapid and of lower cost than molecular (genetic) tests, with current LFDs using antibodies as their recognition units. Herein, we develop a prototype flow-through device (related, but distinct to LFDs), utilizing acetyl neuraminic acid-functionalized, polymer-coated, gold nanoparticles as the detection/capture unit for SARS-COV-2, by targeting the sialic acid-binding site of the spike protein.

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Galectins are potential biomarkers and therapeutic targets. However, galectins display broad affinity towards β-galactosides meaning glycan-based (nano)biosensors lack the required selectivity and affinity. Using a polymer-stabilized nanoparticle biosensing platform, we herein demonstrate that the specificity of immobilised lacto--biose towards galectins can be 'turned on/off' by using site-specific glycan fluorination and in some cases reversal of specificity can be achieved.

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Gold nanorods (GNRs) are a promising platform for nanoplasmonic biosensing. The localised surface plasmon resonance (LSPR) peak of GNRs is located in the near-infrared optical window and is sensitive to local binding events, enabling label-free detection of biomarkers in complex biological fluids. A key challenge in the development of such sensors is achieving target affinity and selectivity, while both minimizing non-specific binding and maintaining colloidal stability.

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Ice binding proteins modulate ice nucleation/growth and have huge (bio)technological potential. There are few synthetic materials that reproduce their function, and rational design is challenging due to the outstanding questions about the mechanisms of ice binding, including whether ice binding is essential to reproduce all their macroscopic properties. Here we report that nanoparticles obtained by polymerization-induced self-assembly (PISA) inhibit ice recrystallization (IRI) despite their constituent polymers having no apparent activity.

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There is an urgent need to understand the behavior of the novel coronavirus (SARS-COV-2), which is the causative agent of COVID-19, and to develop point-of-care diagnostics. Here, a glyconanoparticle platform is used to discover that -acetyl neuraminic acid has affinity toward the SARS-COV-2 spike glycoprotein, demonstrating its glycan-binding function. Optimization of the particle size and coating enabled detection of the spike glycoprotein in lateral flow and showed selectivity over the SARS-COV-1 spike protein.

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Glycomaterials display enhanced binding affinity to carbohydrate-binding proteins due to the nonlinear enhancement associated with the cluster glycoside effect. Gold nanoparticles bearing glycans have attracted significant interest in particular. This is due to their versatility, their highly tunable gold cores (size and shape), and their application in biosensors and diagnostic tools.

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During influenza infection, hemagglutinins (HAs) on the viral surface bind to sialic acids on the host cell's surface. While all HAs bind sialic acids, human influenza targets terminal α2,6 sialic acids and avian influenza targets α2,3 sialic acids. For interspecies transmission (zoonosis), HA must mutate to adapt to these differences.

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Glycan-lectin interactions drive a diverse range of biological signaling and recognition processes. The display of glycans in multivalent format enables their intrinsically weak binding affinity to lectins to be overcome by the cluster glycoside effect, which results in a non-linear increase in binding affinity. As many lectins have multiple binding sites, upon interaction with glycosylated nanomaterials either aggregation or surface binding without aggregation can occur.

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