Biology subjects

Zamora, C.

Publications and source records attributed to Zamora, C..

3 recordsLinked to original sources

bioRxiv2024

Integrated Stress Response Triggered by Excessive Glycosylation Drives Thoracic Aortic aneurysm

Thoracic aortic aneurysms and dissections (TAAD) are marked by degenerative changes in the aortic media. Marfan syndrome is the most common inherited connective tissue disorder associated with TAAD. While vascular smooth muscle cell (VSMC) metabolism is emerging as a targetable driver of aortic aneurysm, surgical interventions remain the primary strategy to prevent aortic dissection. Our research indicates that the hexosamine biosynthetic pathway (HBP), a branch of glycolysis, is upregulated in aortas from the Fbn1C1041G/+ Marfan Syndrome mouse model. Enhancing HBP activity promotes aortic dilation and accumulation glycan-rich extracellular matrix, contributing to aortic medial degeneration in wild-type mice. Mechanistically, fueling HBP activity induces VSMC dysfunction through excessive glycosylation, which activates the Integrated Stress Response (ISR). Pharmacological inhibition of HBP, along with ISR inhibition, successfully reverses aortic dilation and aortic medial degeneration in Fbn1C1041G/+ Marfan Syndrome mouse model. Additionally, Marfan Syndrome patients show elevated levels of HBP metabolites in blood plasma and serum, and heightened HBP-ISR signaling in patients with TAAD. These findings unveil a potential causative role for the HBP-ISR axis in medial degeneration in human TAAD, underscoring the need for evaluating HBP and ISR pathway as novel biomarkers and therapeutic strategies for thoracic aortic aneurysm.

molecular biology↗

bioRxiv2020

Cheetah: a computational toolkit for cybergenetic control

Advances in microscopy, microfluidics and optogenetics enable single-cell monitoring and environmental regulation and offer the means to control cellular phenotypes. The development of such systems is challenging and often results in bespoke setups that hinder reproducibility. To address this, we introduce Cheetah - a flexible computational toolkit that simplifies the integration of real-time microscopy analysis with algorithms for cellular control. Central to the platform is an image segmentation system based on the versatile U-Net convolutional neural network. This is supplemented with functionality to robustly count, characterise and control cells over time. We demonstrate Cheetahs core capabilities by analysing long-term bacterial and mammalian cell growth and by dynamically controlling protein expression in mammalian cells. In all cases, Cheetahs segmentation accuracy exceeds that of a commonly used thresholding-based method, allowing for more accurate control signals to be generated. Availability of this easy-to-use platform will make control engineering techniques more accessible and offer new ways to probe and manipulate living cells.

synthetic biology↗

bioRxiv2020

In vivo Feedback Control of an Antithetic Molecular-Titration Motif in Escherichia coli using Microfluidics

We study both in silico and in vivo the real-time feedback control of a molecular titration motif that has been earmarked as a fundamental component of antithetic and multicellular feedback control schemes in E. coli. We show that an external feedback control strategy can successfully regulate the average fluorescence output of a bacterial cell population to a desired constant level in real-time. We also provide in silico evidence that the same strategy can be used to track a time-varying reference signal where the set-point is switched to a different value halfway through the experiment. We use the experimental data to refine and parameterize an in silico model of the motif that can be used as an error computation module in future embedded or multicellular control experiments.

synthetic biology↗