Biology subjects

Amiel, E.

Publications and source records attributed to Amiel, E..

4 recordsLinked to original sources

bioRxiv2025

Schistosoma mansoni antigen induced innate immune memory features mitochondrial biogenesis and can be inhibited by ovarian produced hormones

We have previously identified that S. mansoni infection induces a unique form of myeloid training that protects male but not female mice from high fat diet induced disease. Here we demonstrate that ovarian derived hormones account for this sex specific difference. Ovariectomy of females prior to infection permits metabolic reprogramming of the myeloid lineage, with BMDM exhibiting carbon source flexibility for cellular respiration, and mice protected from systemic metabolic disease. The innate training phenotype of infection can be replicated by in vivo injection of SEA, and by exposure of bone marrow to SEA in culture prior to macrophage differentiation (Day 0). This protective phenotype is linked to increased chromatin accessibility of lipid and mitochondrial pathways in BMDM including Nrf1 and Tfam, as well as mitochondrial biogenesis. This work provides evidence that S. mansoni antigens induce a unique form of innate training inhibited by ovarian-derived hormones in females.

immunology↗

bioRxiv2023

Enhancing genetically engineered Escherichia coli bioreporters for the detection of buried TNT-based landmines

TNT-based buried landmines are explosive devices consisting of mainly 2,4,6-trinitrotoluene (2,4,6-TNT), but also a 2,4-dinitrotoluene (2,4-DNT) impurity. It is reported that some 2,4-DNT impurity vapors slowly leak through land mine covers and into the soil above them, making this compound a potential indicator for the presence of buried landmines. There are several approaches to identify the presence of chemicals in the environment, one of which is based on a microbial detection system. This approach was previously used to address the challenge of remotely identifying buried landmines by applying genetically engineered microbial whole cell biosensors capable of sensing trace signatures of the explosive compound 2,4,6-TNT and its degradation product, 2,4-DNT. Upon exposure to 2,4-DNT, the genetically engineered bacterial reporter strains, containing a genetic fusion between a sensing element for 2,4-DNT (yqjF gene promoter) and a fluorescence/ bioluminescence reporting element (GFP/ luxCDABE genes), generate a measurable dose-dependent signal within the whole cell biosensor system. This biological component of a comprehensive remote sensing solution was significantly improved after several rounds of random mutagenesis to the yqjF promoter region using a prone-to-error PCR and selection of the best mutants. In the present project further significant improvements were obtained in signal intensity, response time, and in the limit of detection, following an additional round of random mutagenesis. Two new mutants, named A10 and C5, were identified. The new mutants present high induction levels both in terms of Ratio (sample/control) and delta (sample-control), making these strains more amenable to remote detection. To isolate a more sensitive mutant, the 3rd round of random mutagenesis library (about 1000 strains) was re-exposed to lower concentration of 2,4-DNT, but no better candidate was isolated. Possible alternative approaches to lower the detection threshold of the system, such as the use of permeability mutants, are now being tested.

bioengineering↗

bioRxiv2022

Inhibition of Glycogen Metabolism Induces Reactive Oxygen Species-Dependent Apoptosis in Anaplastic Thyroid Cancer

Anaplastic thyroid cancer (ATC) is one of the most lethal solid tumors, yet there are no effective, long-lasting treatments for ATC patients. Most tumors, including tumors of the endocrine system, exhibit an increased consumption of glucose to fuel cancer progression, and some cancers meet this high glucose requirement by metabolizing glycogen. Our goal was to determine if ATC cells metabolize glycogen and if this could be exploited for treatment. We detected glycogen synthase and glycogen phosphorylase (PYG) isoforms in normal thyroid and thyroid cancer cell lines and patient-derived biopsy samples. Inhibition of PYG using CP-91,149 induced apoptosis in ATC cells but not normal thyroid cells. CP-91,149 decreased NADPH levels and induced reactive oxygen species accumulation. CP-91,149 severely blunted ATC tumor growth in vivo. Our work establishes glycogen metabolism as a novel metabolic process in thyroid cells that presents a unique, oncogenic target that could offer an improved clinical outcome. SignificanceGlycogen metabolism plays an important role in combating reactive oxygen species and apoptosis in anaplastic thyroid cancer. Glycogen phosphorylase was inhibited with small molecule inhibitors that limited cell proliferation in vitro and blunted tumor growth in a nude mouse xenograft. This study demonstrates that glycogen metabolism is a viable target in one of the most lethal solid tumors.

cancer biology↗

bioRxiv2020

Schistosoma mansoni infection induces long-lived sex-specific metabolic reprogramming of the myeloid lineage

Despite evidence that helminths protect from metabolic disease, a major gap exists in understanding the underlying mechanism(s). Here we demonstrate that bone marrow derived macrophages (BMDM) from S. mansoni infected male ApoE-/- mice have dramatically increased mitochondrial respiration compared to those from uninfected mice. This change associates with increased glucose and palmitate shuttling into TCA cycle intermediates and decreased accumulation of cellular cholesterol esters. Moreover, systemic metabolic modulation by schistosomes is a function of biological sex, where infection protects ApoE-/- male, but not female, mice from obesity and glucose intolerance. Sex-dependence extends to myeloid cells, where reprogramming leads to opposite cholesterol phenotypes in BMDM from females and males. Finally, the metabolic reprogramming of male myeloid cells is transferrable via bone marrow transplantation to an uninfected host, indicating maintenance of reprogramming in the absence of sustained antigen exposure. This work reveals that S. mansoni systemic reprograming of myeloid metabolism is sex-dependent.

immunology↗