Biology subjects

Aydin, M. S.

Publications and source records attributed to Aydin, M. S..

6 recordsLinked to original sources

bioRxiv2026

Peripheral Axons Form Endoplasmic Reticulum-Rich Conduits With Breast Cancer Cells

Peripheral nerves are active components of the tumor microenvironment, but the physical routes by which sensory axons communicate with cancer cells remain incompletely defined. Here, we show that primary dorsal root ganglion neurons form thin membrane conduits with EMT6 breast cancer cells that contain endoplasmic reticulum (ER). ER-Tracker labeling and neuron-restricted expression of the ER proteins CNPY2 and ATL3 identified ER-rich axonal extensions terminating on cancer cells. Serial-section scanning transmission electron microscopy resolved ER-like membranes within these conduits and at axon-cancer cell interfaces. Scanning electron microscopy and live holotomographic imaging further revealed dynamic contact formation and associated remodeling of the cancer cell surface. These observations define an ER-containing structural interface between sensory axons and cancer cells and provide a framework for testing whether neuronal ER contributes to direct intercellular signaling or material transfer.

cancer biology↗

bioRxiv2026

synpact: accurate, memory-light PacBio HiFi read mapping via a hierarchy of locally-consistent syncmer blocks

MotivationMapping PacBio HiFi reads is a routine task and serves as a central step in many bioinformatics analyses. However, the most accurate long-read mappers have a high memory consumption and are slow. Some light-weight mappers have been proposed for faster runtime, but their accuracy is not comparable to state-of-the-art mappers. With the increasing number of available reference sequences, memory-efficient and fast methods for read mapping without the large accuracy drop are desired. A general trade-off with seed-chain-extend mappers is selecting a single, fixed seed size, which forces a compromise between sensitivity and specificity. ResultsWe present synpact, a long-read mapper that uses several seed sizes (a hierarchy) constructed with Locally Consistent Parsing (LCP) over syncmers. A read is mapped by querying for matches at different levels, followed by sliding window voting. By storing only the coarse upper levels rather than the full hierarchy, the index holds several times fewer entries, while still handling errors by falling back from coarser to finer stored levels at query time. We benchmark synpact against popular long-read mappers on four genomes and different read lengths. For simulated PacBio HiFi data, synpact matches or approaches minimap2 accuracy with higher precision in most cases, while using roughly 5-13x less peak memory (e.g., [~]0.8 GB vs. [~]10.7 GB on human) and mapping faster on large or repetitive genomes (e.g., about 10 to 13 times faster than minimap2 on rye). On real HiFi reads synpact has high concordance with minimap2 across the four genomes, as opposed to the other lightweight long-read mappers. Availability and Implementation: synpact is written in Rust and is available at https://github.com/mahmudsami/synpact

bioinformatics↗

bioRxiv2026

The Joubert syndrome protein CSPP1 is a conserved regulator of vertebrate multiciliogenesis and motile cilia function

Cilia are conserved microtubule-based organelles required for signaling and fluid transport, and their dysfunction causes ciliopathies. Clinical overlap between sensory and motile ciliopathies suggests that primary and motile ciliogenesis depend on shared regulatory modules. Here, we identify Centrosome and Spindle Pole-associated Protein 1 (CSPP1), a microtubule-associated protein mutated in the neurodevelopmental ciliopathy Joubert syndrome, as a conserved regulator of vertebrate multiciliogenesis. Using mouse tracheal epithelial cultures and Xenopus embryonic epidermis, we show that CSPP1 localizes to fibrous granules and deuterosomes during centriole amplification, and to basal bodies and ciliary axonemes in differentiated multiciliated cells. Loss of CSPP1 impairs centriole amplification, basal body apical migration, spacing, and rotational polarity, and is accompanied by disorganization of the apical microtubule network. CSPP1 depletion also disrupts axoneme assembly, resulting in fewer and shorter cilia with ultrastructural defects, reduced ciliary beating, and impaired cilia driven fluid flow in vivo. Together, our findings identify CSPP1 as a conserved regulator of multiciliogenesis and motile cilia function and establish a basis for future work on how shared cytoskeletal pathways may underlie overlapping features of sensory and motile ciliopathies.

cell biology↗

bioRxiv2025

Switching ON Hydrogen Sulfide: A Chemogenetic Toolkit for Spatially Resolved H2S Manipulation

Hydrogen sulfide (H2S) is emerging as a multifaceted signalling molecule that shapes energy metabolism, vascular tone, cancer biology and neurodegeneration. Although fluorescent and genetically encoded sensors now allow real-time H2S imaging, tools for selective control of intracellular H2S remain scarce. Here we benchmark two substrate-based chemogenetic enzymes--the yeast D-amino-acid oxidase (mDAAO) and the Salmonella typhimurium D-cysteine desulfhydrase (stDCyD)--for controlled H2S production. Both enzymes catalyse the conversion of D-cysteine to H2S, yet only mDAAO concomitantly generates hydrogen peroxide, introducing an unwanted oxidative signal. In contrast, stDCyD produces exclusively H2S, thereby offering a clean and efficient means to elevate intracellular H2S in vitro. Our data position stDCyD as the superior chemogenetic actuator for dissecting H2S biology without confounding redox artefacts.

biochemistry↗

bioRxiv2022

Neurons protect themselves by active shrinkage upon axonal transection

Trauma, vascular events, or neurodegenerative processes can lead to axonal injury and eventual transection (axotomy). Neurons can survive axotomy, yet the underlying mechanisms are not fully understood. Excessive water entry into injured neurons poses a particular risk due to swelling and subsequent death. Using in vitro and in vivo neurotrauma model systems based on laser transection, we demonstrated that axotomy triggers actomyosin contraction coupled with calpain activity. As a consequence, neurons shrink acutely to force water out through aquaporin channels preventing swelling and bursting. Inhibiting shrinkage increased the probability of neuronal cell death by about three-fold. These studies reveal a previously unrecognized cytoprotective response mechanism to neurotrauma and offer a fresh perspective on pathophysiological processes in the nervous system. One-Sentence SummaryWhen the axon of a neuron is cut, its soma shrinks to pump out water to avoid deadly swelling.

neuroscience↗

bioRxiv2022

Hexokinase 1b is a novel target for non-small-cell lung cancer

Deregulation of glycolysis is common in non-small cell lung cancer (NSCLC). Hexokinase (HK) enzymes catalyze the phosphoryl-group-transfer in glucose metabolism. There are a very few studies that have begun to reveal the connections between glucose metabolism and splicing programs. Unlike HK2 gene, which is expressed as a single transcript, there are several transcripts of the HK1 gene due to alternative splicing. However, the functional differential roles of HK1 isoforms in glucose metabolism and tumor progression are still elusive. Here, we show that primary NSCLC patient tumor cells metabolically differ from the normal lung epithelium where they display predominant expression of one of the HK1 transcripts, hexokinase1b (HK1b). We utilized CRISPR-Cas9 system to selectively target specific HK1b isoform in NSCLC and show that silencing HK1b in NSCLC cells inhibits tumorigenesis through diminishing glycolysis and proliferation. Our findings constitute the first demonstration of the first biochemical distinction between the HK1 splice variants. Finally, HK1b deletion sensitizes NSCLC cells to standard-of-care, cisplatin treatment, and the combination therapy synergistically increases both apoptotic cell death by cisplatin and autophagic cell death by increased formation of LC3-II associated autophagic vesicles and myelinoid bodies. Notably, loss of HK1b leads to cellular DNA damage, further combination with cisplatin therapy showed significantly increased levels of DNA damage. Importantly, we showed that glycolysis and cisplatin resistance can be restored by adding-back HK1b in HK1b knock-out cells. Our findings reveal that targeting HK1b isoform alone or in combination with cisplatin may represent a novel strategy for NSCLC patients.

cancer biology↗