Ozeri, E. | Search bioRxiv

bioRxiv2026

One-carbon metabolism sustains effector T cell function through cell-surface glycosylation

Folate is a driver of one-carbon metabolism that is essential in T cells. The cellular consequences of its deprivation in CD8+ T cells and impact on anti-tumor function are unknown. Single cell RNA-seq analysis of primary central nervous system lymphoma (PCNSL) patients' tumor samples revealed exhaustion in T cells with high folate metabolism gene expression signature. Functional genomics, metabolite profiling, and glycomics identified disrupted cell surface glycosylation as a major consequence of folate deprivation in CD8+ T cells. Mechanistically, folate deprivation reduced nucleotide sugar levels, perturbed glycosylation, and triggered the apoptotic unfolded protein response. Overexpressing folate transporters in adoptively transferred CD8+ T cells increased intratumoral T cell numbers and reduced exhaustion. Therefore, our data draw a mechanistic line between one-carbon metabolism, cell-surface glycosylation, and anti-tumor T cell function, and support a hypothesis that increased folate uptake can enhance CD8+ T cell function including ex vivo and in vivo CAR-T cells.

cell biology↗

bioRxiv2025

Biologically-constrained insect models enable realistic simulations and improve biomechanical predictions of locomotion

Animal locomotion emerges from the complex interplay of morphology, neural control, and biomechanics, involving both active and passive elements. Insect have attracted much interest, and a rich ecosystem of computational models exists for insect locomotion. However, while active control mechanisms have been extensively studied, obtaining accurate and useful models remains challenging due to limited understanding of how detailed anatomical constraints and passive biomechanical properties shape movement. To address this, we developed anatomically accurate 3D models of the adult desert locust and mole cricket, two orthopteran insects that share a basic body plan but exhibit strikingly different morphologies linked to their habitats and specialized locomotor behaviors -- jumping in locusts versus subterranean digging in mole crickets. We fine-tuned these models using precise morphometric measurements for each major body segment. Furthermore, we quantified passive joint dynamics through high-speed videography of anesthetized locust, revealing a two-phase return motion and history-dependent resting angles. By integrating these biologically grounded constraints into physical simulations, we significantly narrowed the parameter space, resulting in more realistic simulations. Our approach provides new tools for predicting biologically relevant, yet experimentally challenging variables, such as joint torques and contact forces, which contribute directly to the understanding of the underlying biological phenomena. Moreover, these improved simulations offer valuable insight for designing energy-efficient soft robotic systems.

animal behavior and cognition↗