Biology subjects

Zahir, A.

Publications and source records attributed to Zahir, A..

2 recordsLinked to original sources

bioRxiv2025

Engineering Escherichia coli Nissle as safe chassis for delivery of therapeutic peptides

Synthetic biology enables the integration of sophisticated genetic programs into microorganisms, transforming them into potent vehicles for therapeutic applications. Engineering strategies for microorganisms are rapidly evolving, offering promising solutions for cancer therapy, microbiome modulation, digestive health support, and beyond. Developing novel tools to engineer safe, nonpathogenic microbial platforms is essential for advancing clinical therapies. In this work, we present an innovative engineering approach for the probiotic Escherichia coli Nissle (EcN), aimed at creating a safe and efficient chassis for the bioproduction of therapeutics. The EcN endogenous pM1 and pM2 plasmids were cured and re-engineered to introduce a CRISPR-Cas12 chromosome shredding device and a therapeutic-producing genetic circuit, thereby generating a nonproliferative therapeutic-delivery system. Next, we build an AI-based bioinformatic pipeline to predict Anticancer-Cell-Penetrating Peptides (ACCPP) candidates. As a proof-of-concept, a selected ACCPP was produced in the engineered EcN chromosome-shredded (CS) chassis. This strategy yields a robust and controllable platform for the safe production and delivery of therapeutics, paving the way for the future development of microbial therapies and their clinical applications. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=57 SRC="FIGDIR/small/673081v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@2430d4org.highwire.dtl.DTLVardef@1ce2borg.highwire.dtl.DTLVardef@8686cdorg.highwire.dtl.DTLVardef@1fc23fb_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2019

COMT Val158Met polymorphism associated with greater susceptibility to framing effects in healthy older adults

Age-related neural changes may compromise older adults decision-making, increasing their risk of fraud and financial abuse. One manifestation of nonrational influences on decision-making is susceptibility to \"framing effects,\" in which decisions are biased by irrelevant contextual features of how choice information is presented. We investigated whether polymorphisms in genes related to dopamine neurotransmission (COMT) and neurodegeneration (ApoE) influence the susceptibility of older adults to framing effects. We administered an online test of susceptibility to framing effects to a cohort of 113 healthy older adults who had undergone genetic testing for COMT and ApoE genotype. The task required the participant to choose a risky or safe option in pairs of situations that were monetarily equivalent but differed in whether the choice was framed in terms of gains or losses. A general linear model was used to test for associations between inconsistency in choice across the set of choice pairs and these genotypes, controlling for age, education, gender and traditional measures of executive function. While no association to framing effects was found for ApoE, the Valine allele of COMT Val158Met was significantly associated with greater susceptibility to framing, although the association was no longer significant after adjustment for demographic covariates. Our results suggest that greater frontal dopamine concentrations associated with the COMT Met allele are protective against less consistent decision making in older adults. When compared to previous findings in young adults, our findings provide additional support for an inverted-U shaped model of prefrontal dopamine function.

neuroscience↗