Copper is an essential metal nutrient for life that often relies on redox cycling between Cu(I) and Cu(II) oxidation states to fulfill its physiological roles, but alterations in cellular redox status can lead to imbalances in copper homeostasis that contribute to cancer and other metalloplasias with metal-dependent disease vulnerabilities. Copper-...
Cytochrome P450 3A4 (CYP3A4) is a major human drug-metabolizing enzyme, notoriously known for its extreme substrate promiscuity, allosteric behavior, and implications in drug-drug interactions. Despite extensive investigations, the mechanism of ligand binding to CYP3A4 is not fully understood. We determined the crystal structure of CYP3A4 complexed...
The excited-state lifetime is an intrinsic property of fluorescent molecules that can be leveraged for multiplexed imaging. An advantage of fluorescence lifetime-based multiplexing is that signals from multiple probes can be gathered simultaneously, whereas traditional spectral fluorescence imaging typically requires multiple images at different ex...
Cellular biology occurs through myriad interactions between diverse molecular components, many of which assemble in to specific complexes. Various techniques can provide a qualitative survey of which components are found in a given complex. However, quantitative analysis of the absolute number of molecules within a complex (known as stoichiometry) ...
Arbuscular mycorrhizal fungi (AMF) can help mitigate plant responses to water stress, but it is unclear whether AMF do so by indirect mechanisms, direct water transport to roots, or a combination of the two. Here, we investigated if and how the AMF Rhizophagus intraradices transported water to the host plant Avena barbata, wild oat. We used two-com...
The use of micromotors for active drug delivery via oral administration has recently gained considerable interest. However, efficient motor-assisted delivery into the gastrointestinal (GI) tract remains challenging, owing to the short propulsion lifetime of currently used micromotor platforms. Here, we report on an efficient algae-based motor platf...
The permeability of the intestinal barrier is altered in a multitude of gastrointestinal conditions such as Crohn's and coeliac disease. However, the clinical utility of gut permeability is currently limited due to a lack of reliable diagnostic tests. To address this issue, we report a novel technique for rapid, non-invasive measurement of gut perm...
Bioorthogonal cycloaddition reactions between tetrazines and strained dienophiles are widely used for protein, lipid and glycan labelling because of their extremely rapid kinetics. However, controlling this chemistry in the presence of living mammalian cells with a high degree of spatial and temporal precision remains a challenge. Here we demonstra...
Existing tools to detect and visualize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suffer from low selectivity, poor cell permeability, and high cytotoxicity. Here we report a novel self-immolative fluorescent probe (MP590) for the highly selective and sensitive detection of the SARS-CoV-2 main protease (Mpro). This fluorescent pro...
Fluorescence or Förster resonance energy transfer (FRET)-based biosensors are used to monitor activity through molecular pathways inside the cell. Binding of secondary metabolites or enzyme-guided modification of protein targets can be assessed by quantifying the rate of energy transfer between two adequate fluorophores. The AKAR3 sensor contains a...
