Biology subjects

Arbel, M.

Publications and source records attributed to Arbel, M..

5 recordsLinked to original sources

bioRxiv2026

Functional evolution of olfactory indolergic receptors in Diptera

Indole and skatole are widespread semiochemicals mediating mosquito behaviors such as host seeking and oviposition. These cues are detected by a conserved group of odorant receptors (indolORs) first identified in mosquitoes and later found in brachyceran flies, suggesting that indolic detection may represent a broader dipteran trait. To test this, we identified and functionally characterized ten new candidate receptors from eight species spanning the dipteran phylogeny. Phylogenetic and functional analyses indicate that these receptors form a single, well-supported clade with diversified in sensitivity to indole and skatole. Comparative motif analysis revealed four conserved residues correlated with ligand preference. The previously described indole-sensitive receptor from the lepidoteran Helicoverpa armigera OR30 does not exhibit these positions and may have involved sensitivity to indole via another mechanism. These findings underscore the evolutionary trajectory of indolORs across Diptera, revealing both conservation and diversification in indolic odor detection mechanisms.

evolutionary biology↗

bioRxiv2025

AI-directed gene fusing prolongs the evolutionary half-life of synthetic gene circuits

Evolutionary instability is a persistent challenge in synthetic biology, often leading to the loss of heterologous gene expression over time. Here, we present STABLES, a novel gene fusion strategy that links a gene of interest (GOI) to an essential endogenous gene (EG), with a "leaky" stop codon in between. This ensures both selective pressure against deleterious mutations and high expression of the GOI. By leveraging a machine learning (ML) framework, we predict optimal GOI-EG pairs based on bioinformatic and biophysical features, identify linkers likely to minimize protein misfolding, and optimize DNA sequences for stability and expression. Experimental validation in Saccharomyces cerevisiae demonstrated significant improvements in stability and productivity for fluorescent proteins and human proinsulin. The results highlight a scalable, adaptable and organism-agnostic method to enhance the evolutionary stability of engineered strains, with broad implications for industrial biotechnology and synthetic biology.

synthetic biology↗

bioRxiv2025

Computational design of toehold switches in eukaryotes and prokaryotes for efficient post-transcriptional control

The potential to design RNA molecules implementing translational regulated synthetic networks in eukaryotic cells can be harnessed to ramp up the development of various applications in biotechnology, synthetic biology, agriculture and personalized precision therapeutics. In prokaryotes, RNA based translation activation Toehold switches were demonstrated to achieve high fold change in throughput of a desired expression gene in response to different levels of both exogenous and endogenous target trigger RNA molecules. However, low fold changes were reported for such switches applying similar design architecture for eukaryotes. We developed Triggate, a computational pipeline which implements different algorithms for the efficient design and generation of higher on/off ratio optimized toehold switches in prokaryotes and eukaryotes. We also present here a new design architecture for eukaryotic toehold switches which is leaner and simpler. Using our tool and new architecture we report results with a much higher on/off ratio (up to around 13) than achieved before for mRNA toehold switches for eukaryotes. Triggate is available as a web application at http://www.cs.tau.ac.il/~tamirtul/Triggate.

synthetic biology↗

bioRxiv2024

PCNA unloading is crucial for the bypass of DNA lesions by homologous recombination

The DNA Damage Tolerance (DDT) mechanisms allow cells to bypass lesions in the DNA during replication. This allows the cells progress normally through the cell cycle in face of abnormalities in their DNA. PCNA, a homotrimeric sliding clamp complex plays a central role in the coordination of various processes during DNA replication, including the choice of mechanism used during DNA damage bypass. Mono-or poly-ubiquitination of PCNA facilitate an error-prone or an error-free bypass mechanism, respectively. In contrast, SUMOylation recruits the Srs2 helicase, which prevents local homologous recombination. The Elg1 RFC-like complex plays an important role in unloading PCNA from the chromatin. We analyse the interaction of mutations that destabilize PCNA with mutations in the Elg1 clamp unloader and the Srs2 helicase. Our results suggest that in addition to its role as a coordinator of bypass mechanisms, the very presence of PCNA on the chromatin prevents homologous recombination, even in the absence of the Srs2 helicase. Thus, PCNA unloading seems to be a pre-requisite for recombinational repair.

genetics↗

bioRxiv2020

Access to PCNA by Srs2 and Elg1 controls the choice between alternative repair pathways in yeast

During DNA replication stalling can occur when the replicative DNA polymerases encounter lesions or hard-to replicate regions. Under these circumstances the processivity factor PCNA gets ubiquitylated at lysine 164, inducing the DNA damage tolerance (DDT) mechanisms that can bypass lesions encountered during DNA replication. PCNA can also be SUMOylated at the same residue or at lysine 127. Surprisingly, pol30-K164R mutants display a higher degree of sensitivity to DNA damaging agents than pol30-KK127,164RR strains, unable to modify any of the lysines. Here we show that in addition to trans-lesion synthesis and strand-transfer DTT mechanisms, an alternative repair mechanism ("salvage recombination") that copies information from the sister chromatid, is repressed by the recruitment of Srs2 to SUMOylated PCNA. Overexpression of Elg1, the PCNA unloader, or of the recombination protein Rad52 allows its activation. We dissect the genetic requirements for this pathway, as well as the interactions between Srs2 and Elg1.

genetics↗