Biology subjects

Dörr, M.

Publications and source records attributed to Dörr, M..

5 recordsLinked to original sources

bioRxiv2025

Evolutionary Genomics Guides Scalable Coral Probiotics for Climate Resilience

A universal bottleneck limiting probiotic efficacy in medicine, aquaculture, agriculture, and wildlife conservation is uncertain long-term colonization, necessitating repeated administration. We present an evolution-guided framework for probiotic identification based on genomic hallmarks of emerging host dependency, including widespread pseudogenization and insertion sequence proliferation driving genomic restructuring. Applied to coral reefs, we screened over 1,200 coral-associated bacterial isolates and identified Ruegeria MC10 as exhibiting these signatures. Its presence was associated with increased thermal tolerance of a model cnidarian. Following nursery application, MC10 persisted in reef corals for an 8-month monitoring period through a natural bleaching event, improving color retention and retaining algal photosynthesis performance. This work establishes a predictive, scalable pipeline for selecting persistent probiotics, directly addressing a central constraint on microbiome-based interventions across host systems.

microbiology↗

bioRxiv2024

Dual role of BdMUTE during stomatal development in the model grass Brachypodium distachyon

Grasses form morphologically derived, four-celled stomata, where two dumbbell-shaped guard cells (GCs) are flanked by two lateral subsidiary cells (SCs). This innovative form enables rapid opening and closing kinetics and efficient plant-atmosphere gas exchange. The mobile bHLH transcription factor MUTE is required for SC formation in grasses. Yet, if and how MUTE also regulates GC development and if MUTE mobility is required for SC recruitment is unclear. Here, we transgenically impaired BdMUTE mobility from GC to SC precursors in the emerging model grass Brachypodium distachyon. Our data indicates that reduced BdMUTE mobility severely affected the spatiotemporal coordination of GC and SC development. Furthermore, while BdMUTE has a cell-autonomous role in GC division orientation, complete dumbbell morphogenesis of GCs required SC recruitment. Finally, leaf-level gas exchange measurements showed that dosage-dependent complementation of the four-celled grass morphology was mirrored in a gradual physiological complementation of stomatal kinetics. Together, our work revealed a dual role of grass MUTE in regulating GC division orientation and SC recruitment, which in turn was required for GC morphogenesis and the rapid kinetics of grass stomata.

plant biology↗

bioRxiv2020

Expression of a transcript encoding for cytosolic renin in the diseased human heart

Secretory renin promotes hypertrophy, apoptosis, necrosis and fibrosis through angiotensin generation. It has been claimed that local expression of renin contributes to the deleterious effects of the renin-angiotensin system in the heart. Besides the classic renin transcript (renin-a), encoding for secretory renin, a putative brain-specific (renin-b) and a putative lung-specific (renin-c) transcript may exist in human. In contrast to secretory renin, renin-b cannot be secreted, remains within the cytosol and is imported into mitochondria. In contradiction to renin-a, renin-b exerts cardioprotective effects in hearts and in cardiac cells of the rat under ischemia related conditions. To date, available data on cardiac renin expression remain inconsistent. Nobody has yet investigated which renin transcripts are expressed in the human heart. We systematically analyzed the levels of renin transcripts using specific and sensitive nested reverse-transcriptase polymerase chain reactions (RT-PCR) in human ventricular biopsies obtained from patients with heart diseases. In the 33 biopsies available, neither the expression of classic renin-a, nor of the alternative renin-c was detected. In contrast, the renin-b transcript, which was previously classified as brain-specific, was found in 11/33 ventricular biopsies. Our data exclude the expression of secretory renin and indicate that local expression of cytosolic renin but not of secretory renin can play a functional role in the human heart.

physiology↗

bioRxiv2020

Genetic loci associated with prevalent and incident myocardial infarction and coronary heart disease in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

BackgroundGenome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To better understand etiological pathways that might lead to discovery of new treatments or prevention strategies, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome while also exploring associations with common variants. Methods and ResultsUsing samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR=1.80, 95% confidence interval: 1.43, 2.27; P=7.12 x 10-7). Three common variants, rs9349379 in PHACTR1, and rs1333048 and rs4977574 in the 9p21 region, were significantly associated with prevalent CHD. Four common variants (rs4977574, rs10757278, rs1333049, and rs1333048) within the 9p21 locus were significantly associated with incident MI. We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) [≥] 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event. ConclusionThis study confirmed previously reported loci influencing heart disease risk, and one single variant and three genes associated with MI and CHD were newly identified and warrant future investigation.

genetics↗

bioRxiv2019

Genome-wide association study provides new insights into the genetic architecture and pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide1. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained2-4. We report the largest GWAS meta-analysis of HF to-date, comprising 47,309 cases and 930,014 controls. We identify 12 independent variant associations with HF at 11 genomic loci, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function suggesting shared genetic aetiology. Expression quantitative trait analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homeostasis (BAG3), and cellular senescence (CDKN1A). Using Mendelian randomisation analysis we provide new evidence supporting previously equivocal causal roles for several HF risk factors identified in observational studies, and demonstrate CAD-independent effects for atrial fibrillation, body mass index, hypertension and triglycerides. These findings extend our knowledge of the genes and pathways underlying HF and may inform the development of new therapeutic approaches.

genetics↗