Biology subjects

Fox, G.

Publications and source records attributed to Fox, G..

2 recordsLinked to original sources

bioRxiv2023

Discovery of a novel MarR-type transcriptional regulator that controls cell death in Bacillus subtilis biofilms

Pulcherriminic acid (PA) is a cyclic-L-leu-L-leu di-peptide produced by Bacillus subtilis during biofilm formation. When secreted, PA strongly chelates extracellular iron and forms a reddish- brown pigment, pulcherrimin. Production of pulcherriminic acid and formation of pulcherrimin modulate iron homeostasis in B. subtilis. Pulcherriminic acid also functions as an antioxidant to protect cells from increasing oxidative stress during biofilm formation. We previously showed that PA is involved in gene regulation, differentially regulating hundreds of genes in B. subtilis. One of the strongly upregulated genes by PA is yhjH, encoding a putative MarR-type transcription repressor. In this study, we characterized the regulation of the yhjH gene by PA, by PchR, a known transcription repressor for PA biosynthesis, and by YhjH itself. We also found that high expression of yhjH triggers rapid cell lysis in B. subtilis. Results from RNA-seq suggest that YhjH differentially regulates about 180 genes, among which there is a significant number of prophage genes. Lastly, we propose that YhjH be re-named as PcdR, for "pulcherriminic acid cell death regulator".

microbiology↗

bioRxiv2021

Machine learning sequence prioritization for cell type-specific enhancer design

Recent discoveries of extreme cellular diversity in the brain warrant rapid development of technologies to access specific cell populations, enabling characterization of their roles in behavior and in disease states. Available approaches for engineering targeted technologies for new neuron subtypes are low-yield, involving intensive transgenic strain or virus screening. Here, we introduce SNAIL (Specific Nuclear-Anchored Independent Labeling), a new virus-based strategy for cell labeling and nuclear isolation from heterogeneous tissue. SNAIL works by leveraging machine learning and other computational approaches to identify DNA sequence features that confer cell type-specific gene activation and using them to make a probe that drives an affinity purification-compatible reporter gene. As a proof of concept, we designed and validated two novel SNAIL probes that target parvalbumin-expressing (PV) neurons. Furthermore, we show that nuclear isolation using SNAIL in wild type mice is sufficient to capture characteristic open chromatin features of PV neurons in the cortex, striatum, and external globus pallidus. Expansion of this technology has broad applications in cell type-specific observation, manipulation, and therapeutics across species and disease models.

genomics↗