Biology subjects

Matalon, O.

Publications and source records attributed to Matalon, O..

4 recordsLinked to original sources

bioRxiv2026

Drug-centric knowledge graph: representing therapeutic modality, pharmacology and multiscale biology

Biomedical knowledge graphs link targets to mechanisms, diseases and phenotypes, but target-centered representations omit much of what distinguishes therapeutic interventions. We introduce a drug-centric knowledge graph, whose identity model, schema and information-selection priorities are organized around the therapeutic intervention, and a graph built on this design. Each intervention has one identity, linked through relation types shared by all compounds, including target actions, indications, adverse effects, classifications, half-life and direct links to pathways, Gene Ontology concepts, cells and anatomy, and through modality-specific relation types describing small-molecule chemistry, antibody sequences and formats, protein-therapy sequences and antibody-drug conjugate components. Integrating 38 source resources, the graph contains 166,261 nodes of 27 types, 8,106,906 directed edges of 129 relation types and 18,429 compounds in eight therapeutic categories. Construction combines source-specific extraction, compound-identity resolution, language-model-assisted vocabulary and predicate mapping, confidence scoring and connectivity filtering; an expert-reviewed workflow adds investigational therapeutics without altering the base graph. The design offers a reusable template for representing interventions as structured, multimodal objects.

systems biology↗

bioRxiv2021

Inhibition of the SHP-1 activity by PKC-θ regulates NK cell activation threshold and cytotoxicity

Natural Killer (NK) cells play a crucial role in immunity, killing virally infected and cancerous cells. The balance of signals initiated upon engagement of activating and inhibitory NK receptors with cognate ligands determines killing or tolerance. Nevertheless, the molecular mechanisms regulating rapid NK cell discrimination between healthy and malignant cells in a heterogeneous tissue environment are incompletely understood. The SHP-1 tyrosine phosphatase is the central negative NK cell regulator, which dephosphorylates key activating signaling proteins. Though the mechanism by which SHP-1 mediates NK cell inhibition has been partially elucidated, the pathways by which SHP-1 is itself regulated remain unclear. Here, we show that phosphorylation of SHP-1 in NK cells on the S591 residue by PKC-{theta} promotes the inhibited SHP-1 "folded" state. Silencing PKC-{theta} maintains SHP-1 in the active conformation, reduces NK cell activation and cytotoxicity, and promotes tumor progression in-vivo. This study reveals a molecular pathway that sustains the NK cell activation threshold through suppression of SHP-1 activity.

immunology↗

bioRxiv2019

Proteomic analysis reveals the recruitment of intrinsically disordered regions to stress granules

Heat-stress triggers the formation of condensates known as stress granules (SGs), which store non-translating mRNA and stalled translation initiation complexes. To gain a better understanding of SGs, we identified yeast proteins that sediment after heat-shock by mass spectrometry. Heat-regulated proteins are biased toward a subset of abundant proteins that are significantly enriched in intrinsically disordered regions (IDRs). SG localization of over 80 heat-regulated proteins was confirmed using microscopy, including 32 proteins that were not known previously to localize to SGs. We find that several IDRs are sufficient to mediate SG recruitment. Moreover, the diffusive exchange of IDRs within SGs, observed via FRAP, can be highly dynamic while other components remain immobile. Lastly, we showed that the IDR of the Ubp3 deubiquitinase is critical for SG formation. This work confirms that IDRs play an important role in cellular compartmentalization upon stress, can be sufficient for SG incorporation, can remain dynamic in vitrified SGs, and play a vital role during heat-stress.\n\nSummaryThe authors provide an in-depth proteomic study of yeast heat stress granule (SG) proteins. They identified intrinsic disordered regions (IDRs) as one of the main features shared by these proteins and demonstrated IDRs can be sufficient for SG recruitment.

cell biology↗

bioRxiv2018

Reprogramming protein abundance fluctuations in single cells by degradation

Isogenic cells living in the same environment show a natural heterogeneity associated with fluctuations in gene expression. When these fluctuations propagate through cellular regulatory networks, they can give rise to noise regulons, whereby multiple genes fluctuate in a coordinated fashion in single cells. The propagation of these fluctuations has been extensively characterized at the transcriptional level. For example, variations in transcription factor concentration induce correlated fluctuations in the abundance of target gene products. Here, we find that such noise regulons can also stem from protein degradation. We expressed pairs of yellow and red fluorescent proteins, subjected them to differential translation or degradation, and analyzed their fluctuations in single cells. While differential translation had little impact on fluctuations, protein degradation was found to be a dominant contributor. A mathematical model to decompose fluctuations arising from multiple sources of regulation revealed that cells with higher protein production capacity also exhibited higher protein degradation capacity. This association uncouples fluctuations in protein abundance from fluctuations in production rate, and can generate orthogonal noise regulons even for proteins relying on the same transcriptional program.

systems biology↗