Biology subjects

Dohai, B.

Publications and source records attributed to Dohai, B..

3 recordsLinked to original sources

bioRxiv2026

Conserved metabolic vulnerabilities across pathogenic coronaviruses nominate host-directed therapeutic targets

Pathogenic coronaviruses profoundly rewire host cell metabolism to support viral replication, yet whether these metabolic alterations expose shared and actionable vulnerabilities remains unclear. By integrating transcriptomic profiles from cells infected with SARS-CoV, SARS-CoV-2, and MERS-CoV with genome-scale metabolic models, we identify conserved and virus-specific metabolic perturbations affecting mitochondrial transport, nucleotide biosynthesis, fatty acid metabolism, and redox balance. Despite distinct transcriptional responses, all three viruses converge on a limited set of metabolic reactions whose flux ranges deviate strongly from healthy states. Using a network-based predictive framework, we systematically identify gene-pair perturbations that restore perturbed reaction fluxes toward non-infected metabolic states. Predicted rescue mechanisms reveal shared metabolic dependencies across coronaviruses, as well as time-dependent virus-specific vulnerabilities, and nominate druggable host targets. Notably, several top predictions align with independent experimental and clinical evidence, including metabolic interventions shown to reduce viral replication or disease severity in COVID-19 patients. Together, our results define conserved metabolic rescue pathways in coronavirus infection and provide a general strategy for identifying host-directed therapeutic opportunities from transcriptomic data. HighlightsO_LICoronaviruses converge on shared metabolic vulnerabilities in host cells C_LIO_LINiTRO predicts gene pairs that rescue viral-induced metabolic states C_LIO_LIMitochondrial transport emerges as a key pan-coronavirus target C_LIO_LITop predictions validated by clinical trials and in vitro evidence C_LI eTOC BlurbDohai et al. develop NiTRO, a network-based algorithm that integrates coronavirus-induced transcriptomic changes with genome-scale metabolic models to identify gene-pair perturbations capable of rescuing infected metabolic states. The approach reveals shared and virus-specific druggable metabolic vulnerabilities, with top predictions corroborated by clinical evidence.

systems biology↗

bioRxiv2025

Multi-omics decipher the molecular mechanisms driving high-lipid production in an artificially-evolved Chlamydomonas mutant

Enhancing lipid accumulation in microalgae is critical for commercial viability but often compromises growth. We previously identified an artificially evolved Chlamydomonas reinhardtii mutant (H5) that retains wild-type growth (CC-503) while producing significantly more lipids. Here, we present multi-omic analyses that elucidate the molecular basis of this phenotype. Whole-genome sequencing revealed over 3,000 mutations in H5, including 45 in protein-coding genes (e.g., phosphofructokinase, acyl-carrier protein, glycerol kinase). Six corresponding CLiP insertion mutants also showed elevated lipid content. Transcriptomics revealed upregulation of key genes for glycolysis, nutrient uptake, and proliferation (e.g., pyruvate carboxylase, carbonic anhydrase) under nutrient-replete conditions. Metabolomics identified a striking increase in malonate, a metabolite that supports fatty acid synthesis and cell proliferation. Epigenomic profiling showed hypomethylation in triacylglycerol (TAG) biosynthesis genes and hypermethylation in energy balance regulators. Together, these data suggest that accelerated glycolysis and streamlined metabolism drive lipid accumulation in H5 without compromising growth. Our findings provide a blueprint for engineering high-lipid microalgal strains for industrial applications. HIGHLIGHTSO_LIHigh-lipid Chlamydomonas mutant (H5) exhibits cancer-like metabolism: pseudo-hypoxia and nutrient deprivation response C_LIO_LIMulti-omics reveals 45 high-impact mutations synergistically enhance lipid production in H5 C_LIO_LISix CLiP mutants of H5-disrupted genes showed significantly increased lipid content C_LIO_LIMalonate levels increased 10-fold in H5, indicating altered mitochondrial function C_LIO_LIH5 upregulates glycolytic genes while maintaining wild-type growth rates C_LIO_LITranscriptomes from H5 and CC-503 converge after nitrogen deprivation despite replete-state differences C_LIO_LIH5 shows altered lipid composition with increased TAG diversity, decreased DAGs C_LIO_LIEpigenomic profiling reveals 14,720 differentially methylated transcribed regions in H5 C_LI

genomics↗

bioRxiv2023

A gut meta-interactome map reveals modulation of human immunity by microbiome effectors

The molecular mechanisms by which the gut microbiome influences human health remain largely unknown. Pseudomonadota is the third most abundant phylum in normal gut microbiomes. Several pathogens in this phylum can inject so-called virulence effector proteins into host cells. We report the identification of intact type 3 secretion systems (T3SS) in 5 - 20% of commensal Pseudomonadota in normal human gut microbiomes. To understand their functions, we experimentally generated a high-quality protein-protein meta-interactome map consisting of 1,263 interactions between 289 bacterial effectors and 430 human proteins. Effector targets are enriched for metabolic and immune functions and for genetic variation of microbiome-influenced traits including autoimmune diseases. We demonstrate that effectors modulate NF-{kappa}B signaling, cytokine secretion, and adhesion molecule expression. Finally, effectors are enriched in metagenomes of Crohns disease, but not ulcerative colitis patients pointing toward complex contributions to the etiology of inflammatory bowel diseases. Our results suggest that effector-host protein interactions are an important regulatory layer by which the microbiome impacts human health.

microbiology↗