Biology subjects

Schechter, M.

Publications and source records attributed to Schechter, M..

5 recordsLinked to original sources

bioRxiv2025

Vibrio spp. dominate the microbiome of the endosymbiotic algae in healthy coral tissues

Coral reefs are rapidly declining due to climate change, and natural recovery mechanisms can no longer keep pace. Coral probiotics have emerged as a promising restoration tool, yet their broad application is limited by our incomplete understanding of long-term microbial associations crucial to coral health. Microbes closely associated with the coral algal symbionts (Symbiodiniaceae) are particularly promising candidates, given their potential to enhance algal function and host resilience. Although recent studies have begun to characterize these Symbiodiniaceae-associated microbial communities, methodological differences in algal cell purification have led to inconsistent results. Here, we compared multiple sample processing steps to generate Symbiodiniaceae-enriched fractions from clonal fragments of Acropora nobilis, and examined the resulting microbial communities. We consistently detected members of Flavobacteraceae, Rhodobacteraceae, Rhizobiaceae, and the genus Marinobacter. Strikingly, Vibrio species dominated the Symbiodiniaceae fractions across protocols. We isolated and sequenced 11 Vibrio strains enriched in these fractions and identified genes related to both virulence and putative beneficial traits, including vitamin biosynthesis and antioxidant production. Despite confirming their high potential for virulence, the persistent association, spatial proximity to Symbiodiniaceae, and presence of genes suggesting beneficial functions point to possible mutualistic roles for these Vibrio strains within the coral holobiont. This work highlights the value of fraction-based sampling for resolving microbiome structure, and emphasizes the need to reassess the ecological roles of key microbial taxa. By advancing our understanding of Symbiodiniaceae-bacteria interactions, this work provides a foundation for exploring microbial contributions to coral health and resilience.

microbiology↗

bioRxiv2025

α-Synuclein Activates the PI3K/AKT Pathway to Drive Lipid Droplets Accumulation: Implications for Parkinson's Disease

Growing evidence supports a metabolic component in Parkinsons disease (PD). - Synuclein (-Syn), a protein central to the onset and progression of PD, facilitates the accumulation of neuronal lipid droplets, which are implicated in disease pathology. We report that AKT is hyper-phosphorylated in PD brains and show that -Syn enhances p110 activity by facilitating palmitoylated Ras localization to the plasma membrane, driving lipid droplet accumulation through PI3K/AKT/mTOR and PPAR{gamma} activation. Phosphorylation of -Syn at Ser129 correlates positively with the localization of Ras to the membrane fraction and with accumulation of lipid droplets. In-vivo treatment of young, asymptomatic -SynA53T transgenic mice with GDC-0084 (paxalisib), a blood- brain barrier-permeable PI3K inhibitor, restored healthy AKT activity levels, reduced levels of PSer129 and -Syn oligomers, decreased neuronal lipid droplet accumulation, and promoted lysosomal clustering. These findings establish a role for -Syn in p110 activation during early, asymptomatic stages of the disease and highlight the therapeutic potential of PI3K inhibition as a disease-modifying strategy. Highlight-Syn activates PI3K/AKT by promoting the localization of palmitoylated Ras to membranes, linking metabolic dysfunction to PD.

neuroscience↗

bioRxiv2022

Directed evolution of generalist biosensors for single ring aromatics

Biosensors can accelerate the engineering of new biosynthetic pathways. Phloroglucinol is a platform chemical of wide utility that can be produced at limited titers in Escherichia coli. Starting from the TetR family repressor RolR that is responsive to the related compound resorcinol, we were able to employ a combined selection and screen to identify variants that had greatly improved activities with phloroglucinol (EC50 for phloroglucinol of 131 uM, relative to an estimated 42 mM for wild-type RolR). The variants obtained were further screened with a panel of similar single ring aromatics, and several were found to be generalists, consistent with the hypothesis that both natural and directed evolution tend to first create semi-specific pockets prior to further optimization for new function

synthetic biology↗

bioRxiv2020

Light into the darkness: Unifying the known and unknown coding sequence space in microbiome analyses

Genes of unknown function are among the biggest challenges in molecular biology, especially in microbial systems, where 40%-60% of the predicted genes are unknown. Despite previous attempts, systematic approaches to include the unknown fraction into analytical workflows are still lacking. Here, we propose a conceptual framework and a computational workflow that bridge the known-unknown gap in genomes and metagenomes. We showcase our approach by exploring 415,971,742 genes predicted from 1,749 metagenomes and 28,941 bacterial and archaeal genomes. We quantify the extent of the unknown fraction, its diversity, and its relevance across multiple biomes. Furthermore, we provide a collection of 283,874 lineage-specific genes of unknown function for Cand. Patescibacteria, being a significant resource to expand our understanding of their unusual biology. Finally, by identifying a target gene of unknown function for antibiotic resistance, we demonstrate how we can enable the generation of hypotheses that can be used to augment experimental data.

microbiology↗

bioRxiv2020

α-Synuclein facilitates endocytosis by elevating the steady-state levels of phosphatidylinositol 4,5-bisphosphate

-Synuclein (-Syn) is a protein implicated in the pathogenesis of Parkinsons disease (PD). It is an intrinsically disordered protein that binds acidic phospholipids. Growing evidence supports a role for -Syn in membrane trafficking, including, mechanisms of endocytosis and exocytosis, although the exact role of -Syn in these mechanisms is currently unclear. Here we have investigated the role of -Syn in membrane trafficking through its association with acidic phosphoinositides (PIPs), such as phosphatidylinositol 4,5-bisphosphate (PI4,5P2) and phosphatidylinositol 3,4-bisphosphate (PI3,4P2). Our results show that -Syn colocalizes with PIP2 and the phosphorylated active form of the clathrin adaptor AP2 at clathrin-coated pits. Using endocytosis of transferrin, an indicator of clathrin mediated endocytosis (CME), we find that -Syn involvement in endocytosis is specifically mediated through PI4,5P2 levels. We further show that the rate of synaptic vesicle (SV) endocytosis is differentially affected by -Syn mutations. In accord with their effects on PI4,5P2 levels at the plasma membrane, the PD associated E46K and A53T mutations further enhance SV endocytosis. However, neither A30P mutation, nor Lysine to Glutamic acid substitutions at the KTKEGV repeat domain of -Syn, that interfere with phospholipid binding, affect SV endocytosis. This study provides evidence for a critical involvement of PIPs in -Syn-mediated membrane trafficking. Significance Statement-Synuclein (-Syn) protein is known for its causative role in Parkinsons disease. -Syn is normally involved in mechanisms of membrane trafficking, including endocytosis, exocytosis and synaptic vesicles cycling. However, a certain degree of controversy regarding the exact role of -Syn in these mechanisms persists. Here we show that -Syn acts to increase plasma membrane levels PI4,5P2 and PI3,4P2 to facilitate clathrin mediated and synaptic vesicles endocytosis. Based on the results, we suggest that -Syn interactions with the acidic phosphoinositides facilitate a shift in their homeostasis to support endocytosis.

neuroscience↗