Biology subjects

Majer, T.

Publications and source records attributed to Majer, T..

3 recordsLinked to original sources

bioRxiv2025

Engineering Infrared Light Detection in Blind Human Retina Using Ultrasensitive Human TRPV1 Channels

Engineering infrared light sensitivity in the blind human retina could restore visual function in patients with regional retinal degeneration. However, current approaches are complex and contain non-human biological components. Using rational protein design we engineered human TRPV1 channels ({Delta}786-840) with temperature sensitivity shifted from 45 to 41{degrees}C that enabled near-infrared light- induced heat activation of mammalian cells at close to physiological temperatures. When expressed in ganglion cells of human retinal explants, {Delta}786-840 TRPV1 generated robust spiking responses to brief near-infrared light-induced temperature transients. Additionally, increasing intensity of radiation evoked graded responses correlating with increasing firing frequencies. Unlike previous approaches that used non-human TRPV1 channels, which risk immune reactions and a multicomponent system that poses barriers to clinical implementation, this single component human-derived approach eliminates immunogenicity concerns, addressing a major challenge to clinical translation, and allow gene delivery using adeno-associated viral vectors.

bioengineering↗

bioRxiv2024

SOD1 controls neutrophil oxidative burst and microbial killing

AbstractNeutrophils are immune cells specialized in producing large amounts of reactive oxygen species (ROS) to kill microbes. However, the mechanisms by which these cells regulate the balance of different ROS species and mitigate oxidative stress remain unclear. Here, we demonstrate that superoxide dismutase 1 (SOD1) plays a crucial role in ROS formation and antimicrobial activity in neutrophils. Our findings reveal that SOD1 modulates the ratio of superoxide (O2-) to hydrogen peroxide (H2O2) during the ROS burst, thereby supporting myeloperoxidase (MPO) enzymatic activity. By employing biochemical, cell biological, and genetic approaches, we show that SOD1 is crucial for ROS formation during NETosis and microbial infections, as it reduces oxidative stress and enables complete neutrophil activation. Impairment of SOD1 activity increases cysteine oxidation and lipid peroxidation. Neutrophils isolated from a patient with a SOD1 mutation exhibit decreased ROS production and impaired neutrophil extracellular trap (NET) formation. Our findings suggest that SOD1 is a novel regulatory factor in the oxidative burst that enables the full immunological response of neutrophils.

immunology↗

bioRxiv2023

Bioinformatics-Guided Discovery of Biaryl-Tailored Lasso Peptides

Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that feature an isopeptide bond and a distinct lariat fold. A growing number of secondary modifications have been described that further decorate lasso peptide scaffolds. Using genome mining, we have discovered a pair of lasso peptide biosynthetic gene clusters (BGCs) that include cytochrome P450 genes. Here, we report the structural characterization of two unique examples of (C-N) biaryl-containing lasso peptides. Nocapeptin A, from Nocardia terpenica, is tailored with Trp-Tyr crosslink while longipepetin A, from Longimycelium tulufanense, features Trp-Trp linkage. Besides the unusual bicyclic frame, longipepetin A receives an S-methylation by a new Met methyltransferase resulting in unprecedented sulfonium-bearing RiPP. Our bioinformatic survey revealed P450(s) and further maturating enzyme(s)-containing lasso BGCs awaiting future characterization.

biochemistry↗