Biology subjects

Akbari, E.

Publications and source records attributed to Akbari, E..

5 recordsLinked to original sources

bioRxiv2026

Enhanced DNA Scanning and Target Specificity via Motif Sequestration

Sequence-specific DNA-binding proteins must efficiently locate their target sequences within large, structurally heterogeneous genomes while avoiding nonproductive off-target interactions. Here, we show that an autoinhibitory conformational state of the site-specific recombinase Cre lowers nonspecific DNA-binding affinity to promote one-dimensional DNA scanning while suppressing off-target assembly of recombinogenic complexes. Recent studies indicate that the C-terminal segment of Cre transiently adopts a sequestered conformation that occludes the catalytic domain's DNA-binding surface. Using NMR spectroscopy, single-molecule fluorescence microscopy, and optical trapping, we investigated how this conformational equilibrium regulates target search. NMR measurements reveal that the sequestered state predominates in the absence of DNA and persists at noncognate sites, whereas binding to cognate loxP sequences relieves autoinhibition. Single-molecule tracking demonstrates that full-length Cre undergoes processive one-dimensional diffusion and transitions to stable binding upon cognate-site recognition, whereas C-terminal truncation impairs scanning efficiency by arresting diffusion. These findings demonstrate how transient motif sequestration coordinates target search with site-specific complex assembly, suggesting a general mechanism by which DNA-modifying enzymes balance search efficiency and target specificity.

biophysics↗

bioRxiv2025

Diverse Visual Experience Promotes Integrated Representations and Mitigates Bias in Deep Neural Networks for Face Perception

Humans are experts at recognizing faces, yet this expertise is not uniform: people perceive faces from familiar facial groups more accurately than those from unfamiliar ones--a phenomenon known as the Other-Race Effect (ORE). Diverse facial exposure mitigates this bias, but how it reorganizes face representations to support cross-group recognition remains unclear. To address this question, we combined controlled training variation in deep convolutional neural networks (CNNs) with analyses of representational geometry, lesioning, and human behavioral data. CNNs trained exclusively on either Asian or White faces reproduced ORE-like biases, whereas a CNN trained on both groups showed reduced bias and balanced recognition performance. Critically, representational similarity analyses and lesioning revealed largely overlapping feature spaces across groups, indicating an integrated representational organization. Trial-by-trial comparisons with human choices further showed that the dual-trained CNN best captured human face-matching behavior across both Asian and White participants, outperforming single-trained networks on cross-group trials. Together, these findings show that diverse visual experience promotes an integrated representational geometry that supports cross-group generalization, providing a computational account of how exposure diversity may shape human face representations.

neuroscience↗

bioRxiv2025

Linker histone H1.0 loads onto nucleosomes through multiple pathways that are facilitated by histone chaperones

Linker histone H1 is an essential chromatin architectural protein that compacts chromatin into transcriptionally silent regions by interacting with nucleosomal and linker DNA, while rapidly exchanging in vivo. How H1 targets nucleosomes while being dynamic remains unanswered. Using a single-molecule strategy, we investigated human H1.0 interactions with DNA and nucleosomes. H1.0 directly binds nucleosomes and naked DNA with a preference toward nucleosomes. DNA-bound H1.0 exhibited a range of bound lifetimes with both mobile and immobile states, where the mobile H1.0 did not load onto nucleosomes. The histone chaperone Nap1 facilitated H1.0-nucleosome loading by enabling H1.0 loading through DNA sliding, reducing DNA resident times without impacting nucleosome resident times, increasing mobility along DNA, and targeting H1.0 loading onto the nucleosome dyad. These findings reveal linker histones load onto nucleosomes through multiple distinct mechanisms that are facilitated by chaperones to regulate chromatin accessibility.

biophysics↗

bioRxiv2022

Multiplexed Detection of Molecular Interactions with DNA Origami Engineered Cells in 3-D Collagen Matrices

The interactions of cells with signaling molecules present in their local microenvironment maintain cell proliferation, differentiation, and spatial organization, and mediate progression of diseases such as metabolic disorders and cancer. Real-time monitoring of the interactions between cells and their extracellular ligands in a 3-D microenvironment can inform detection and understanding of cell processes and development of effective therapeutic agents. DNA-origami technology allows for the design and fabrication of biocompatible and 3-D functional nanodevices via molecular self-assembly for various applications including molecular sensing. Here, we report a robust method to monitor live cell interactions with molecules in their surrounding environment in a 3-D tissue model using a microfluidic device. We used a DNA origami Cell Sensing Platform (CSP) to detect two specific nucleic acid sequences on the membrane of B cells and dendritic cells. We further demonstrated real-time detection of biomolecules with the DNA sensing platform on the surface of dendritic cells in a 3-D microfluidic tissue model. Our results establish the integration of live cells with membranes engineered with DNA nanodevices into microfluidic chips as a highly capable biosensor approach to investigate subcellular interactions in physiologically relevant 3-D environments under controlled biomolecular transport.

bioengineering↗

bioRxiv2019

Competing Fluid Forces Control Endothelial Sprouting in a 3-D Microfluidic Vessel Bifurcation Model

Sprouting angiogenesis, the infiltration and extension of endothelial cells from pre-existing blood vessels, helps orchestrate vascular growth and remodeling. It is now agreed that fluid forces, such as laminar shear stress due to unidirectional flow in straight vessel segments, are important regulators of angiogenesis. However, regulation of angiogenesis by the different flow dynamics that arise due to vessel branching, such as impinging flow stagnation at the base of a bifurcating vessel, are not well understood. Here we used a recently developed 3-D microfluidic model to investigate the role of the flow conditions that occur due to vessel bifurcations on endothelial sprouting. We observed that bifurcating fluid flow located at the vessel bifurcation point suppresses the formation of angiogenic sprouts. Similarly, laminar shear stress at a magnitude of [~]3 dyn/cm2 applied in the branched vessels downstream of the bifurcation point, inhibited the formation of angiogenic sprouts. In contrast, co-application of [~]1 {micro}m/s average transvascular flow across the endothelial monolayer with bifurcating fluid flow and laminar shear stress induced the formation of angiogenic sprouts. These results suggest that transvascular flow imparts a competing effect against bifurcating fluid flow and laminar shear stress in regulating endothelial sprouting. To our knowledge, these findings are the first report on the stabilizing role of bifurcating fluid flow on endothelial sprouting. These results also demonstrate the importance of local flow dynamics due to branched vessel geometry in determining the location of sprouting angiogenesis.

bioengineering↗