Biology subjects

Leibovitch, M.

Publications and source records attributed to Leibovitch, M..

3 recordsLinked to original sources

bioRxiv2026

Phylogenetic relationship between birds and their magneto-microbiome

Animals from a wide taxonomic range can sense earths magnetic field, however the underlying mechanism remains one of sensory-biology greatest mysteries. One hypothesis suggests that Magnetotactic bacteria (MTB) serve as the underlying mechanism. This hypothesis predicts that MTB will be detected in animal microbiomes and might show a phylogenetic relationship with their hosts. We examined the phylogenetic relationship between various MTB species across 4,048 avian species using databases of MTB genetic presence across the tree of life and an avian phylogenetic tree. We documented 12 genera of MTB in association with 185 avian species. Three genera, Magnetospirillum, Magnetovibrio and Solidesulfovibrio, were found at relative high prevalence of positive samples (84%, 33%, 12% respectively). Further, Magnetospirillum showed a significant phylogenetic relationship with avian species in general and specifically within Psittaciformes, and Passeriformes. Our results demonstrate the power of harnessing the newly published MTB-database, with specific host-related queries. This analysis, to the best of our knowledge has never been done, and could be replicated across the animal kingdom. The relationship detected suggests an evolutionary and ecological relationship between MTB and avian hosts. These results are consistent with the symbiotic magnetic sensing hypothesis and highlights the potential role of microbiome in sensory physiology.

ecology↗

bioRxiv2025

WEE1 inhibitors trigger GCN2-mediated activation of the integrated stress response

The WEE1 kinase negatively regulates CDK1/2 to control DNA replication and mitotic entry. Genetic factors that determine sensitivity to WEE1 inhibitors (WEE1i) are largely unknown. A genome-wide insertional mutagenesis screen revealed that mutation of EIF2A, a translation regulator, sensitized to WEE1i. Mechanistically, WEE1i treatment triggers a translational shut-down, which is lethal in combination with the reduced translation of EIF2AKO cells. A genome-wide CRISPR-Cas9 screen revealed that inactivation of integrated stress response (ISR) kinases GCN1/2 rescued WEE1i-mediated cytotoxicity. WEE1i induced GCN2 activation, ATF4 upregulation, and altered ribosome dynamics. Loss of the collided ribosome sensor ZNF598 conversely increased sensitivity to WEE1i. Notably, the ISR was not required for WEE1i to induce DNA damage, premature mitotic entry or sensitization to DNA-damaging chemotherapeutics. ISR activation was independent of CDK1/2 activation. Importantly, WEE1i-mediated ISR activation was independent of WEE1 presence, pointing at off-target effects, which are shared by multiple chemically distinct WEE1i. This response was also observed in peripheral blood mononuclear cells. Importantly, low-dose WEE1 inhibition did not induce ISR activation, while it still synergized with PKMYT1 inhibition. Taken together, WEE1i triggers toxic ISR activation and translational shutdown, which can be prevented by low-dose or combination treatments, while retaining the cell cycle checkpoint-perturbing effects.

cancer biology↗

bioRxiv2024

The oncofetal protein IMP1 regulates the transcriptomic landscape to drive early events in pancreatic cancer progression and growth

Background & AimsPancreatic ductal adenocarcinoma (PDAC) has a dismal 5-year survival rate of 12% - the lowest of all malignancies. This is partially due to late diagnosis, as early stages of the disease, including the process of acinar to ductal metaplasia (ADM) are not presently detectable. Insulin-like growth factor 2 mRNA binding protein (IMP)1 is an oncofetal protein implicated in cancer progression. Here, we aimed to determine its role in the early stages of PDAC development and in the maintenance of the malignant phenotype. MethodsIMP1 expression was analyzed in surgical PDAC specimens and in pancreatic tissue derived from KPC mice. Murine ductal organoids expressing the KrasG12D mutant were treated with the IMP1 inhibitor BTYNB and RNAseq performed. The function of IMP1 targets was analyzed in an ADM model and the effect of IMP1 silencing on the growth of PDAC cells was evaluated in vivo. ResultsWe found high expression of IMP1 in precancerous lesions of human and murine PDAC, but not in the normal pancreas. Blockade of IMP1 function impeded murine ADM and ductal organoid growth and profoundly altered the transcriptional landscape of the organoids, reducing the expression of cytokine-cytokine receptor interactors, cell adhesion and cell invasion mediators such as Card11, Gkn3, Il13ra2, Mmp9, and Vcam1. Gastrokine-3 and IL-13 in turn, enhanced the ADM process. Finally, IMP1 silencing in PDAC cells inhibited their metastatic outgrowth in mice. ConclusionsIMP1 is a master regulator of early events in PDAC progression and a potential biomarker and target for this disease.

cancer biology↗