Biology subjects

Bashth, O.

Publications and source records attributed to Bashth, O..

3 recordsLinked to original sources

bioRxiv2025

Predicting and Controlling Collective Fate in Multicellular Systems

Collective behavior is a defining property of multicellular systems, where coordinated outcomes emerge from local cell-cell interactions. Yet the quantitative rules linking single-cell decision-making to tissue-scale organization remain poorly resolved. Here, we develop a quantitative framework that defines an order parameter predicting when initially disordered colonies undergo a transition to ordered fate alignment and when minimal, localized inputs can redirect their collective state. This analysis reveals a distinct control regime in which multicellular assemblies become susceptible to a single engineered "guide" cell. We validate these predictions by introducing guide cells that integrate into unperturbed colonies and redirect fate patterns within the theoretically defined control windows. Together, these results connect single-cell decision rules to emergent tissue-level organization and establish a generalizable biological control strategy in which a minority engineered subset can reliably redirect the developmental trajectory of a much larger multicellular population. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=65 SRC="FIGDIR/small/693804v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@37baeforg.highwire.dtl.DTLVardef@d1d86aorg.highwire.dtl.DTLVardef@d7375eorg.highwire.dtl.DTLVardef@1741e9a_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOSummary figure:C_FLOATNO Emergence, Scaling, and Control of Multicellular Collective Order. (A) Cell-number-dependent collective order. Sparse colonies lack coordination and yield disordered fate distributions; dense colonies exhibit coordinated, ordered outcomes. (B) Collective order rises with colony compactness ({propto} cell density) and collapses across colony radii R onto a single curve. (C) Once coordination emerges, a single "guide cell" can steer fate-analogous to a sheepdog guiding a flock. The herding efficacy exhibits a biphasic window versus cell number. C_FIG

systems biology↗

bioRxiv2023

A multi-kingdom genetic barcoding system for precise target clone isolation

Clonal heterogeneity underlies diverse biological processes, including cancer progression, cell differentiation, and microbial evolution. Cell tagging strategies with DNA barcodes have recently enabled analysis of clone size dynamics and clone-restricted transcriptomic landscapes of heterogeneous populations. However, isolating a target clone that displays a specific phenotype from a complex population remains challenging. Here, we present a new multi-kingdom genetic barcoding system, CloneSelect, in which a target cell clone can be triggered to express a reporter gene for isolation through barcode-specific CRISPR base editing. In CloneSelect, cells are first barcoded and propagated so their subpopulation can be subjected to a given experiment. A clone that shows a phenotype or genotype of interest at a given time can then be isolated from the initial or subsequent cell pools stored throughout the experimental timecourse. This novel CRISPR-barcode genetics platform provides many new ways of analyzing and manipulating mammalian, yeast, and bacterial systems. TeaserA multi-kingdom CRISPR-activatable barcoding system enables the precise isolation of target barcode-labeled clones from a complex cell population.

synthetic biology↗

bioRxiv2021

Bioaffinity-based Surface Immobilization of Antibodies to Capture Endothelial Colony-forming Cells

Maximizing the re-endothelialization of vascular implants such as prostheses or stents has the potential to significantly improve their long-term performance. Endothelial progenitor cell capture stents with surface-immobilized antibodies show significantly improved endothelialization in the clinic. However, most current antibody-based stent surface modification strategies rely on antibody adsorption or direct conjugation via amino or carboxyl groups which leads to poor control over antibody surface concentration and/or molecular orientation, and ultimately bioavailability for cell capture. Here, we assess the utility of a bioaffinity-based surface modification strategy consisting of a surface-conjugated cysteine-tagged protein G molecules that immobilize Immunoglobulin G (IgG) antibodies via the Fc domain to capture circulating endothelial colony-forming cells (ECFCs). The cysteine-tagged protein G was grafted onto aminated substrates at different concentrations as detected by an enzyme-linked immunosorbent assay and fluorescence imaging. Different IgG antibodies were successfully immobilized on the protein G-modified surfaces and higher antibody surface concentrations were achieved compared to passive adsorption methods. Surfaces with immobilized antibodies targeting endothelial surface proteins, such as CD144, significantly enhanced the capture of circulating ECFCs in vitro compared to surfaces with non-endothelial specific antibodies such as anti-CD14. This work presents a potential avenue for enhancing the clinical performance of vascular implants by using covalent grafting of protein G to immobilize IgG antibodies more effectively. Table of Contents O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/449631v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@310b10org.highwire.dtl.DTLVardef@1cd8722org.highwire.dtl.DTLVardef@6306a0org.highwire.dtl.DTLVardef@1481eae_HPS_FORMAT_FIGEXP M_FIG C_FIG Antibody immobilization via surface-conjugated recombinant cysteine-protein G provides an effective approach to capture circulating therapeutic cells.

bioengineering↗