Biology subjects

Maoz, B. M.

Publications and source records attributed to Maoz, B. M..

5 recordsLinked to original sources

bioRxiv2026

Cross-species analysis of GNB1 I80T encephalopathy: conserved developmental, epileptic and neuronal transcriptome signatures

GNB1 encephalopathy (GNB1E) is a rare neurodevelopmental disorder caused by mutations in GNB1 gene encoding the G protein subunit G{beta}1. Mechanisms linking these variants to neurological dysfunction remain unclear. We investigated the prevalent p.Ile80Thr (I80T) variant using combined clinical, cellular, and in vivo approaches. Longitudinal evaluation of a GNB1E patient revealed developmental delay, progressive peripheral spasticity, and epilepsy with Spike-Wave Activation in Sleep. Heterozygous knock-in Gnb1I80T/+ mice exhibited disease-relevant phenotypes, including impaired early development, mild adult motor and cognitive deficits and epileptiform cortical spike-and-wave discharges. Transcriptomic analysis identified 323 genes concordantly dysregulated in mouse cortex and cortical human neuronal cultures from patient-derived induced pluripotent cells. This gene set was enriched for ion-channel function, epilepsy-associated genes, and Gs/adenylyl cyclase signaling pathway. Our integrated analysis establishes the first cross-species model for GNB1E, suggests common neurological mechanisms and molecular pathways linked to GNB1E, and provides a framework for mechanistic and therapeutic studies. TeaserConserved human/mouse neurological and transcriptomic signatures in GNB1 encephalopathy.

physiology↗

bioRxiv2026

The Sniffbot: A biohybrid robot for active sensing-based odor localization and discrimination

The detection, identification and localization of volatile compounds are of critical importance for various applications, ranging from gas leak detection to drug and explosive sensing. Current technologies--such as gas chromatography-mass spectrometry and e-noses--are limited by slow analysis, low mobility, and reduced sensitivity and adaptability, making them unsuitable for real-time odor localization in real-world settings. Here, we present Sniffbot: an autonomous, mobile biohybrid robotic sensory system that overcomes these challenges by harnessing the extraordinary olfactory capabilities of the desert locust antenna, an advanced olfactory sensor, that generates odorant-specific electrophysiological responses to numerous odorants. Our Sniffbot platform consists of a compact robotic vehicle onto which we have assembled: (i) a sensing module, comprising a locust antenna and a miniaturized electrophysiology system; (ii) a "sniffing" module, which actively samples air in the environment, creating a timed airflow over the antenna, preventing the antenna from becoming habituated to odorant stimuli; and (iii) a decision-making module that analyzes the sensory input in real time to navigate or identify odors. Sniffbots movements are controlled by an odorant-search algorithm coupled with the sniffing module. This enables Sniffbot to detect and localize odors independently of wind-induced odorant gradients, and thus to be used in challenging windless environments. The Trident, a novel search algorithm, outperforms several commonly used algorithms in localizing the odorant source. We further demonstrate Sniffbots ability to discriminate a target odor among others. Our results demonstrate the potential of augmenting biological sensors with autonomous robotic components for next-generation chemical sensing and environmental monitoring.

bioengineering↗

bioRxiv2024

Engineered chitosan-derived nanocarrier for efficient siRNA delivery to peripheral and central neurons

Gene therapy using small interfering RNA (siRNA) holds promise for treating neurological disorders by silencing specific genes, such as the phosphatase and tensin homolog (PTEN) gene, which restricts axonal growth. Yet, delivering siRNA to neurons efficiently is challenging due to premature degradation and unspecific delivery. Chitosan-based delivery systems have shown great potential due to their well-established biocompatibility. However, their limited transfection efficiency and lack of neuronal tropism require further modification. Building on our previous successes with neuron-targeted DNA delivery using chitosan, a novel approach for siRNA delivery aimed at PTEN downregulation is proposed. This involves using thiolated trimethyl chitosan (TMCSH)-based siRNA nanoparticles functionalized with the neurotropic C-terminal fragment of the tetanus neurotoxin heavy chain (HC) for efficient delivery to both peripheral and central neurons. These polyplexes demonstrated suitable physicochemical properties, biocompatibility, and no adverse effects on neuronal electrophysiology. Diverse neuronal models, including 3D ex vivo cultures and microfluidics, confirmed polyplexes efficiency and neurospecificity. HC targeting significantly enhanced nanoparticle neuronal binding, and live cell imaging revealed five times faster retrograde transport along axons. Furthermore, siRNA delivery targeting PTEN promoted axonal outgrowth in embryonic cortical neurons. Thus, these polyplexes represent a promising platform for siRNA delivery, offering potential for clinical translation and therapeutic applications.

bioengineering↗

bioRxiv2024

Unveiling the potential of neuron-targeted dendriplexes for siRNA delivery using a PNS-CNS-on-Chip

Neurological disorders, a leading global cause of death, encompass conditions affecting the peripheral and central nervous systems (PNS and CNS, respectively). Limited axon regeneration is a significant challenge in these disorders, and it is linked to proteins like PTEN. RNA-based therapeutics, particularly siRNAs, hold potential for silencing these inhibitory pathways, but their clinical application is hindered by poor stability and cellular uptake. Our study addressed this challenge with the development of novel, fully biodegradable dendritic nanoparticles designed specifically for neuron targeting. These nanoparticles were functionalized with the neurotropic binding domain of tetanus toxin, enhancing selective neuronal targeting and cellular internalization. We demonstrated that these dendriplexes not only maintain biocompatibility and efficient siRNA delivery in neuronal cultures but also significantly enhance axonal growth, as shown in microfluidic models. In a groundbreaking PNS-CNS-on-Chip, dendriplexes exhibited effective migration from PNS to CNS neurons, highlighting their potential for targeted therapeutic delivery. This study pioneers the application of microfluidics to demonstrate the CNS targeting of dendriplexes, paving the way for innovative treatments in the field of nanomedicine.

bioengineering↗

bioRxiv2021

Effect of SARS-CoV-2 proteins on vascular permeability

SARS-CoV-2 infection leads to severe disease associated with cytokine storm, vascular dysfunction, coagulation, and progressive lung damage. It affects several vital organs, seemingly through a pathological effect on endothelial cells. The SARS-CoV-2 genome encodes 29 proteins, whose contribution to the disease manifestations, and especially endothelial complications, is unknown. We cloned and expressed 26 of these proteins in human cells and characterized the endothelial response to overexpression of each, individually. Whereas most proteins induced significant changes in endothelial permeability, nsp2, nsp5_c145a (catalytic dead mutant of nsp5) and nsp7 also reduced CD31, and increased von Willebrand factor expression and IL-6, suggesting endothelial dysfunction. Using propagation-based analysis of a protein-protein interaction (PPI) network, we predicted the endothelial proteins affected by the viral proteins that potentially mediate these effects. We further applied our PPI model to identify the role of each SARS-CoV-2 protein in other tissues affected by COVID-19. Overall, this work identifies the SARS-CoV-2 proteins that might be most detrimental in terms of endothelial dysfunction, thereby shedding light on vascular aspects of COVID-19.

cell biology↗