Biology subjects

Furnish, M.

Publications and source records attributed to Furnish, M..

3 recordsLinked to original sources

bioRxiv2026

Developing synthetic auxin-based trans-kingdom signaling

Synthetic trans-kingdom signaling systems with tunable transduction properties provide a unique avenue to explore how communication between organisms coordinate behaviors without the confounding complexity of natural systems. However, existing trans-kingdom signaling systems suffer from either toxic signal molecules, a need for rare precursors for signal generation, or transduction machinery which is either species-specific or cannot be easily tuned. This limits their capacity to be broadly applied across kingdoms and their utility as a model system to study trans-kingdom interactions. In this work we elucidate the design principles for a trans-kingdom signaling system based on the plant phytohormone, Indole 3-Acetic Acid (auxin), that overcomes these challenges. We demonstrate how auxin biosynthesis can be engineered into a model sender organism, the cyanobacteria Synechococcus elongatus PCC 7942, and how this signal can be tuned with low leak and high dynamic range. We also show these signals can be connected to gene expression using tunable synthetic auxin-responsive signaling systems across multiple kingdoms. We demonstrate that S. elongatus generated auxin signals can tune gene expression in co-cultured Saccharomyces cerevisiae via auxin-induced degradation. Additionally, we show that when the S. elongatus are associated with the roots of the model plant, Arabidopsis thaliana, the auxin they generate can control gene expression via auxin-responsive synthetic transcription factors expressed from the plants genome. Taken together, our results demonstrate the design principles for a tunable auxin-based trans-kingdom signaling system that can be broadly applied across species.

synthetic biology↗

bioRxiv2026

High-throughput engineering of ligand-activated splicing ribozyme through domain insertion

Domain insertion is an established method to engineer ligand-mediated control of activity in protein scaffolds. Whether this strategy can be systematically applied to large, structured RNAs remains unclear. In this study, we investigated the feasibility of engineering ligand-activated splicing ribozymes (LASRs) from group I catalytic introns. Using domain-insertion profiling coupled with high-throughput screening, we mapped the nucleotide-resolution landscape of aptamer insertion across the ribozyme and identified sites that support robust ligand-dependent control. We showed LASRs function across multiple kingdoms of life, including diverse species of bacteria and even fungi, and can be used to regulate various genetic outputs. Finally, we integrated LASRs with a genetic recorder that writes information into ribosomal RNA, enabling sequencing-based recovery of intracellular chemical signals from microbial consortia. This work establishes LASRs as an RNA-based inducible control platform for sensing diverse chemical inputs, regulating the expression of diverse genes of interest, and recording intracellular information.

synthetic biology↗

bioRxiv2021

MIRO2 regulates prostate cancer cell growth via GCN1-dependent stress signaling

There is a continued need to identify novel therapeutic targets to prevent the mortality associated with prostate cancer. In this context, we discovered a novel mitochondrial signaling pathway that controls androgen-independent and androgen-sensitive prostate cancer cell growth. Mitochondrial Rho GTPase 2 (MIRO2) mRNA was upregulated in prostate cancer compared to localized tumors, and higher MIRO2 levels were correlated with poor patient survival. Using human cell lines that represent AR-independent or androgen-sensitive prostate cancer, we show that MIRO2 depletion impaired cell growth, colony formation and tumor growth in mice. Network analysis of MIRO2s binding partners identified metabolism, cell cycle, and cellular responses to extracellular stimuli amongst the top over-represented pathways. The top hit on our screen was General Control Non-derepressible 1 (GCN1). GCN1 was overexpressed in prostate cancer and MIRO2-GCN1 interacted in prostate cancer cell lines and in primary prostate cancer cells. Our results showed that MIRO2 is necessary for efficient GCN1-mediated GCN2 kinase activation and signaling, triggering translation of the transcription factor ATF4. Importantly, MIRO2 controlled ATF4 levels and transcriptional activity both in amino acid replete and depleted conditions. Furthermore, MIRO2s effect on regulating prostate cancer cell growth was partially mediated by ATF4. Finally, activation of GCN2 and ATF4 expression were correlated with MIRO2 expression in prostate cancer xenografts. Overall, we propose a new mechanism driving prostate cancer growth of both AR-independent and androgen-sensitive tumors.

cancer biology↗