Biology subjects

Farooq, A.

Publications and source records attributed to Farooq, A..

3 recordsLinked to original sources

bioRxiv2026

In vivo spatial coordination with synthetic paracrine signaling

The immune system uses paracrine signaling to spatially confine potent responses such as inflammation. A bio-orthogonal synthetic paracrine system could enable engineering of analogous multicellular circuits in which different cell types coordinate their functions in a spatially organized fashion. Here, using the plant hormone auxin as a bio-orthogonal chemical signal, we introduce programmable paracrine circuits that distribute sensing and effector functions to different cell types to spatially restrict responses in mouse xenografts. Cells engineered to express auxin biosynthetic genes generated auxin-dense regions with tunable length scales in vivo. This localized signaling ability enabled design of a multicellular sentinel-effector system, in which THP-1 sentinel cells conditionally produce auxin in regions expressing the tumor-specific antigen EGFRvIII, and Jurkat effector cells respond by locally modulating the activity of a chimeric antigen receptor (CAR). This two-cell type system was able to achieve localized activation of engineered effector cells in vivo. These results establish a foundation for engineering multicellular therapeutic systems that focus responses in specific tissue contexts or disease sites.

Synthetic Biology↗

bioRxiv2025

Systematic molecular glue drug discovery with a high-throughput effector protein remodeling platform

Realising the promise of new medicines that operate through a targeted molecular glue-induced degradation mechanism requires systematic tools that can uncover the relevant principles of neomorphic protein-protein interactions. Whilst some monovalent glue degraders have been found through serendipity, the rules for small molecule attributes and the pairs or complexes of proteins that are amenable to drug-induced proximity control remain poorly articulated. Here we introduce a new approach to address this by using programmed libraries of intramolecularly edited proteins to expand protein surface landscapes and trigger new druggable interactions. We show that effector proteins, such as the E3 ligase Cereblon, can be engineered to provoke neomorphic activity by inducing the degradation of new client proteins and that these de novo interactions provide a blueprint from which new small molecule degraders can be built. As a demonstration of the approach, we use the platform to identify new non-IMiD molecular glue degraders of the oncology target GSPT1. SUMMARYO_LIMolecular glues are a highly important and promising new form of therapeutic agent, but rationalising their discovery has so far been impossible C_LIO_LIGlueSEEKER screening enables prospective monovalent drug discovery by using high-throughput deep mutational scanning to re-engineer the function of effector proteins like E3 ligases C_LIO_LIWe used this approach to enable the computational discovery of small molecule glues which degrade the oncology target GSPT1 and show how the technology can be used across new targets C_LI

bioengineering↗

bioRxiv2025

Integrative Assessment of Pathogenic Bacterial Genomes: Insights from Quality Metrics

Genomic resources are increasingly being shared in public databases for reusability. Ensuring the quality of these resources is crucial, as the presence of low-quality genomes can compromise downstream analyses and propagate across databases. However, there is a lack of consistent and comprehensive assessments for such genomes in public genomic databases. This study focused on the quality assessment of 474 pathogenic bacterial genomes submitted from South Korea, with a particular emphasis on the integrative application of completeness, contiguity, and accuracy metrics. The genomes were ranked based on cumulative scores derived from individual metrics. High-ranked genomes consistently exceeded defined thresholds, including 98% completeness for complete single-copy BUSCO, less than 200 contigs, N50 values greater than 65 kb, and unmapped reads below 2%. Notably, positive and negative linear associations were observed among these quality metrics, emphasizing their integrative utilization, although the consistency across all metrics varied. The findings emphasize the importance of conducting comprehensive genome assessments and implementing stringent quality control measures in public databases to enhance the reliability and usefulness of pathogenic bacterial genomic data. By addressing these issues, we can improve the overall quality of public genomic resources and ensure their suitability for diverse downstream applications.

microbiology↗