Biology subjects

Farrell, M. V.

Publications and source records attributed to Farrell, M. V..

3 recordsLinked to original sources

bioRxiv2026

Low CAR affinity enhances T-cell synapse dynamics and activation

Low affinity chimeric antigen receptors (CARs) can clinically outperform high-affinity variants, yet the molecular mechanisms underlying affinity-dependent activity remain unclear. Here, we show that low CAR affinity enables faster CAR cluster motion, which is central to T-cell activation. We compared low-affinity CAT and high-affinity FMC63 CARs signaling at different stages of activation on supported lipid bilayers functionalized with defined CD19 densities. At low CAR expression on dense CD19 bilayers, low-affinity CAT CARs formed more mature and dynamic synapses, recruited ZAP70 more efficiently, and showed faster microcluster motion. These proximal signaling changes were accompanied by stronger calcium flux and increased NFAT nuclear translocation. Our data support a model in which weaker, lower-affinity CAR-antigen interactions promote receptor turnover, microcluster mobility, and signaling-adaptor recruitment, thereby enhancing downstream signal propagation. Our work provides a mechanistic basis for the superior functional performance reported for affinity-tuned CD19 CAR-T cells.

biophysics↗

bioRxiv2026

A non-living, microbe-based surface coating promotes tubeworm and coral settlement

A major barrier to scaling marine restoration and aquaculture is the lack of reliable tools to induce invertebrate larvae to settle and metamorphose when and where needed. Although microbial cues are known to induce metamorphosis in many invertebrates, existing methods rely on natural biofilms that are variable, difficult to standardize, and unsuitable for large-scale deployment. Here we introduce ReefTiles, a non-living bacterial coating that preserves inductive activity from metamorphosis-stimulating marine bacteria in a stable, reproducible format. Using both tubeworm and coral larvae, we show that dried and inactivated bacterial films retain full settlement-inducing capacity, matching or exceeding live biofilms while eliminating concerns associated with releasing viable microbes into the environment. Viability assays confirm inactivation, and the coating adheres reliably to common substrate materials. Because ReefTiles can be manufactured and stored at scale and tailored to different inductive strains, they provide a practical microbe-based biotechnology for enhancing larval settlement in reef restoration, sustainable aquaculture, and engineered marine infrastructure.

bioengineering↗

bioRxiv2023

A modular plasmid toolkit applied in marine Proteobacteria reveals functional insights during bacteria-stimulated metamorphosis

A conspicuous roadblock to studying marine bacteria for fundamental research and biotechnology is a lack of modular synthetic biology tools for their genetic manipulation. Here, we applied, and generated new parts for, a modular plasmid toolkit to study marine bacteria in the context of symbioses and host-microbe interactions. To demonstrate the utility of this plasmid system, we genetically manipulated the marine bacterium Pseudoalteromonas luteoviolacea, which stimulates the metamorphosis of the model tubeworm, Hydroides elegans. Using these tools, we quantified constitutive and native promoter expression, developed reporter strains that enable the imaging of host-bacteria interactions, and used CRISPR interference (CRISPRi) to knock down a secondary metabolite and a host-associated gene. We demonstrate the broader utility of this modular system for rapidly creating and iteratively testing genetic tractability by modifying marine bacteria that are known to be associated with diverse host-microbe symbioses. These efforts enabled the successful transformation of twelve marine strains across two Proteobacteria classes, four orders and ten genera. Altogether, the present study demonstrates how synthetic biology strategies enable the investigation of marine microbes and marine host-microbe symbioses with broader implications for environmental restoration and biotechnology.

synthetic biology↗