Biology subjects

Schleicher, E.

Publications and source records attributed to Schleicher, E..

4 recordsLinked to original sources

bioRxiv2026

A nucleotide-triggered molecular switch orchestrating septin polymerization

Septins are conserved cytoskeletal GTP-binding proteins that form higher-order structures critical for cytokinesis and polarized growth across opisthokonts. In budding yeast and humans, four homologous septins assemble into hetero-octameric protofilaments through alternating interactions between adjacent G-domains (G-interface) or N- and C-termini (NC-interface), which then polymerize end-to-end into filaments. How nucleotide binding and hydrolysis control filament assembly has remained elusive. We uncover a septin-specific mechanism in which nucleotide binding stabilizes the monomeric G-interface and primes it for protofilament formation. Cryo-EM and DEER spectroscopy reveal nucleotide-induced conformational changes that engage the G-interface and enable an NC-compatible conformation absent in the nucleotide-free state. In vitro binding and reconstitution assays confirm that G-interface formation is strictly nucleotide-dependent and required for subsequent NC-interface assembly. These findings establish unidirectional allosteric signaling from the G-to the NC-interface, revealing the molecular basis for controlled septin protofilament assembly.

molecular biology↗

bioRxiv2025

Optically detected and radio wave-controlled spin chemistry in cryptochrome

Optically addressable spin systems, such as nitrogen-vacancy centers in diamond, have been widely studied for quantum sensing applications. In this work, we demonstrate that certain flavoproteins -- specifically cryptochrome and iLOV -- which generate spin correlated radical pairs upon optical excitation, also exhibit optically detected magnetic resonance (ODMR). Remarkably, the iLOV protein, commonly used in cellular imaging, displays ODMR contrast approaching 50%. We present initial applications including widefield magnetic field sensing and spatial modulation of photoluminescence using radiofrequency pulses and magnetic field gradients. Our results establish radical pairs in proteins as a novel platform for optically addressable spin systems, offering the key advantages of molecular designability and genetic encodability. Moreover, due to the spin-selective nature of radical pair chemistry, the results lay the groundwork for future radiofrequency-based manipulation of biological systems.

biophysics↗

bioRxiv2025

Light-induced conformational switching and magnetic sensitivity of Drosophila cryptochrome

Cryptochromes are flavoproteins with a number of established and proposed biological functions based on their sensitivity to light. Amongst the latter is the possibility that cryptochromes mediate the geomagnetic compass sense used by migratory birds as a navigational cue. This hypothesis rests on a magnetically sensitive photochemical reaction of the flavin chromophore in which a series of electron transfers within the protein scaffold ultimately generates a signal propagated within the central nervous system of the animal. Although there is a good understanding of the photochemistry and the electron transfer pathway, the protein-mediated mechanisms of signal transduction are still unclear. Here we have examined the response of Drosophila melanogaster cryptochrome - DmCRY, an archetypal cryptochrome - to photochemical activation by means of molecular dynamics simulations, hydrogen-deuterium exchange mass spectrometry, and cavity ring-down spectroscopy. We were able to measure the dynamics of DmCRY at near-residue level resolution, revealing a reversible, long-lived, blue-light induced conformational change in the C-terminal tail of the protein. This putative signalling state was validated using different illumination conditions, and by examining DmCRY variants in which the electron transfer chain was disrupted by point mutation. Our results show how the photochemical behaviour of the flavin chromophore generates a state of DmCRY that may act as a key primer for modulating downstream interactions.

biophysics↗

bioRxiv2019

An Integrated Framework for Genome Analysis Reveals Numerous Previously Unrecognizable Structural Variants in Leukemia Patients' Samples

While genomic analysis of tumors has stimulated major advances in cancer diagnosis, prognosis and treatment, current methods fail to identify a large fraction of somatic structural variants in tumors. We have applied a combination of whole genome sequencing and optical genome mapping to a number of adult and pediatric leukemia samples, which revealed in each of these samples a large number of structural variants not recognizable by current tools of genomic analyses. We developed computational methods to determine which of those variants likely arose as somatic mutations. The method identified 97% of the structural variants previously reported by karyotype analysis of these samples and revealed an additional fivefold more such somatic rearrangements. The method identified on average tens of previously unrecognizable inversions and duplications and hundreds of previously unrecognizable insertions and deletions. These structural variants recurrently affected a number of leukemia associated genes as well as cancer driver genes not previously associated with leukemia and genes not previously associated with cancer. A number of variants only affected intergenic regions but caused cis-acting alterations in expression of neighboring genes. Analysis of TCGA data indicates that the status of several of the recurrently mutated genes identified in this study significantly affect survival of AML patients. Our results suggest that current genomic analysis methods fail to identify a majority of structural variants in leukemia samples and this lacunae may hamper diagnostic and prognostic efforts.

genomics↗