Biology subjects

Law, T.

Publications and source records attributed to Law, T..

3 recordsLinked to original sources

bioRxiv2026

Streptomyces enrichment in roots during drought is uncoupled from plant benefit and is driven by host suppression of iron uptake and immunity

Drought reshapes plant root microbiota, yet the mechanistic drivers and consequences of this observation remain unclear. We discovered that suppression of host immunity and iron homeostasis is required for Streptomyces enrichment in roots during drought across diverse soils. Genetic and physiological manipulation of these host pathways confirmed their requirement in modulating Streptomyces root enrichment. Drought-induced suppression of iron uptake was conserved across the [~]160 My monocot-eudicot divergence. Some Streptomyces strains enhanced plant growth and rescued iron uptake under drought. These benefits were uncoupled from Streptomyces root enrichment. They were instead shaped by intra-Streptomyces antagonism. We propose a two-step model: drought-driven down regulation of host iron and immune pathways enriches Streptomyces, while intra-genus dynamics fine-tune strain-level assembly and functional outcomes. Our data refine the idea that Streptomyces are enriched in roots during drought in response to a plant cry for help and consequently contribute to alleviation of this abiotic stress.

plant biology↗

bioRxiv2020

Chromatin potential identified by shared single cell profiling of RNA and chromatin

Cell differentiation and function are regulated across multiple layers of gene regulation, including the modulation of gene expression by changes in chromatin accessibility. However, differentiation is an asynchronous process precluding a temporal understanding of the regulatory events leading to cell fate commitment. Here, we developed SHARE-seq, a highly scalable approach for measurement of chromatin accessibility and gene expression within the same single cell. Using 34,774 joint profiles from mouse skin, we develop a computational strategy to identify cis-regulatory interactions and define Domains of Regulatory Chromatin (DORCs), which significantly overlap with super-enhancers. We show that during lineage commitment, chromatin accessibility at DORCs precedes gene expression, suggesting changes in chromatin accessibility may prime cells for lineage commitment. We therefore develop a computational strategy (chromatin potential) to quantify chromatin lineage-priming and predict cell fate outcomes. Together, SHARE-seq provides an extensible platform to study regulatory circuitry across diverse cells within tissues.

genomics↗

bioRxiv2020

Thousands of novel unannotated proteins expand the MHC I immunopeptidome in cancer

Tumor epitopes - peptides that are presented on surface-bound MHC I proteins - provide targets for cancer immunotherapy and have been identified extensively in the annotated protein-coding regions of the genome. Motivated by the recent discovery of translated novel unannotated open reading frames (nuORFs) using ribosome profiling (Ribo-seq), we hypothesized that cancer-associated processes could generate nuORFs that can serve as a new source of tumor antigens that harbor somatic mutations or show tumor-specific expression. To identify cancer-specific nuORFs, we generated Ribo-seq profiles for 29 malignant and healthy samples, developed a sensitive analytic approach for hierarchical ORF prediction, and constructed a high-confidence database of translated nuORFs across tissues. Peptides from 3,555 unique translated nuORFs were presented on MHC I, based on analysis of an extensive dataset of MHC I-bound peptides detected by mass spectrometry, with >20-fold more nuORF peptides detected in the MHC I immunopeptidomes compared to whole proteomes. We further detected somatic mutations in nuORFs of cancer samples and identified nuORFs with tumor-specific translation in melanoma, chronic lymphocytic leukemia and glioblastoma. NuORFs thus expand the pool of MHC I-presented, tumor-specific peptides, targetable by immunotherapies.

cancer biology↗