Biology subjects

Otte, J.

Publications and source records attributed to Otte, J..

7 recordsLinked to original sources

bioRxiv2025

Fungal and algal lichen symbionts show different transcriptional expression patterns in two climate zones

In the lichen symbiosis, the fungal and algal partners constitute a closely integrated system. The combination of fungal and algal partners changes along climate gradients in many species, and is expected to be adaptive. However, the functional mechanisms behind this symbiosis-mediated environmental adaptation are unknown. We investigate which transcriptional profiles are associated with specific fungal-algal symbiont pairings found in lichens from high elevation (cold temperate) and low elevation (Mediterranean) sites. Using laboratory-acclimatized thalli, we find that lichen fungal and algal symbionts show variable expression profiles between high- and low-elevation individuals: circadian- and temperature-associated genes for fungi and light-responsive genes for algae show site- specific patterns. We also find that high- and low-elevation individuals differentially express sugar and carbohydrate transporters in both fungal and algal symbionts, pointing to symmetrical and climate-dependent carbohydrate transport mechanisms between the symbionts. A light pulse treatment identified asymmetries between fungal and algal light response, with high- and low-elevation fungal symbionts but only low-elevation algal symbionts responding to the light pulse. We identify light responsive genes in fungal symbionts that may differ from those previously described for other fungi. Together, these results shed light on functional differences between environmentally specialized lichen individuals, made up of niche-specific partner combinations.

ecology↗

bioRxiv2023

The importance of experimental design for studying the vector competence of Ornithodoros ticks for African swine fever virus: a meta-analysis of published evaluations

African Swine Fever (ASF) is a highly economically devastating viral disease for swine. Soft ticks of the genus Ornithodoros are involved in its epidemiology, as vectors and natural reservoirs of African Swine Fever Virus (ASFV). The vector competence of Ornithodoros ticks for ASFV has been mainly studied by mimicking natural tick-to-pig transmission pathways through experimental infections in the laboratory. By reviewing the original research studies dating back to the 1960s on the vector competence of Ornithodoros for ASFV, we estimated the vector competence of 10 tick species in association with 38 viral strains resulting in 51 tick-virus associations. This assessment emphasized the extensive range of protocol designs employed and their impact on the success of tick infection with ASFV. Our results call for standardised procedures in vector competence experiments to facilitate further investigation and reduce potential experimental bias. In particular, we recommend the use of late nymphs or adult ticks from a laboratory colony to achieve efficient infection rates. In addition, viral inoculation should be carried out by blood meal rather than by injection, and preference should be given to high titre blood. Finally, detection of viral DNA should be performed 2 months after inoculation to distinguish between successful replication and residual virus in the tick.

ecology↗

bioRxiv2022

A candidate gene cluster for the bioactive natural product gyrophoric acid in lichen-forming fungi

Natural products of lichen-forming fungi are structurally diverse and have a variety of medicinal properties. Despite this, they a have limited implementation in industry, because the corresponding genes remain unknown for most of the natural products. Here we implement a long-read sequencing and bioinformatic approach to identify the biosynthetic gene cluster of the bioactive natural product gyrophoric acid (GA). Using 15 high-quality genomes representing nine GA-producing species of the lichen-forming fungal genus Umbilicaria, we identify the most likely GA cluster and investigate cluster gene organization and composition across the nine species. Our results show that GA clusters are promiscuous within Umbilicaria, with only three genes that are conserved across species, including the PKS gene. In addition, our results suggest that the same cluster codes for different but structurally similar NPs, i.e., GA, umbilicaric acid and hiascic acid, bringing new evidence that lichen metabolite diversity is also generated through regulatory mechanisms at the molecular level. Ours is the first study to identify the most likely GA cluster, and thus provides essential information to open new avenues for biotechnological approaches to producing and modifying GA and similar lichen-derived compounds. We show that bioinformatics approaches are useful in linking genes and potentially associated natural products. Genome analyses help unlocking the pharmaceutical potential of organisms such as lichens, which are biosynthetically diverse but slow growing, and difficult to cultivate due to their symbiotic nature. ImportanceThe implementation of natural products in the pharmaceutical industry relies on the possibility of modifying the natural product (NP) pathway to optimize yields and pharmacological effects. Characterization of genes and pathways underlying natural product biosynthesis is a major bottleneck for the use of natural products in the pharmaceutical industry. Genome mining is a promising and relatively cost- and time-effective approach to exploit unexplored NP resources for drug discovery. In this study, we identify the most likely gene cluster for the lichen-forming fungal depside gyrophoric acid in nine Umbilicaria species. This compound shows cytotoxic and antiproliferative properties against several cancer cell lines, and is also a broad-spectrum antimicrobial agent. We identify the putative GA cluster from nine Umbilicaria species. This information paves the way for generating GA analogs with modified properties by selective activation/deactivation of genes.

genomics↗

bioRxiv2022

Phylogenomics reveals the evolutionary origin of lichenization in chlorophyte algae

Mutualistic symbioses have contributed to major transitions in the evolution of life. Here, we investigate the evolutionary history and the molecular innovations at the origin of lichens, which are a symbiosis established between fungi and green algae or cyanobacteria. We de novo sequence the genomes or transcriptomes of 12 lichen algal symbiont (LAS) and closely related non-symbiotic algae (NSA) to improve the genomic coverage of Chlorophyte algae. We then perform ancestral state reconstruction and comparative phylogenomics. We identify at least three independent gains of the ability to engage in the lichen symbiosis, one in Trebouxiophyceae and two in Ulvophyceae, confirming the convergent evolution of the lichen symbioses. A carbohydrate-active enzyme from the glycoside hydrolase 8 (GH8) family was identified as a top candidate for the molecular-mechanism underlying lichen symbiosis in Trebouxiophyceae. This GH8 was acquired in lichenizing Trebouxiophyceae by horizontal gene transfer, concomitantly with the ability to associate with lichens fungal symbionts (LFS) and is able to degrade polysaccharides found in the cell wall of LFS. These findings indicate that a combination of gene family expansion and horizontal gene transfer provided the basis for lichenization to evolve in chlorophyte algae.

plant biology↗

bioRxiv2021

DHODH is an independent prognostic marker and potent therapeutic target in neuroblastoma

Despite intensive therapy, children with high-risk neuroblastoma are at risk of treatment failure. We applied a pan-cancer, multi-omic system approach to evaluate metabolic vulnerabilities in human neuroblastoma. By combining metabolomics, CRISPR screen and gene expression data from more than 700 solid tumor cell lines, we identified DHODH, a critical enzyme in pyrimidine synthesis, as a potential novel treatment target in neuroblastoma. Of note, DHODH inhibition is currently under clinical investigation in patients with hematologic malignancies. In neuroblastoma, DHODH expression was identified as an independent risk factor for aggressive disease, and high DHODH levels correlated to worse overall and event-free survival. A subset of high-risk neuroblastoma tumors with the highest DHODH expression was associated with a dismal prognosis, with a 5-year survival of less than 10%. In neuroblastoma cell lines, DHODH gene dependency was found to correlate with MYCN dependency, rendering these cell lines highly sensitive to DHODH inhibition in vitro. In xenograft and transgenic neuroblastoma mouse models, tumor growth was dramatically reduced, and survival extended following treatment with the DHODH inhibitor brequinar. A combination of brequinar and temozolomide cured the majority of transgenic TH-MYCN neuroblastoma mice, indicating a highly active clinical combination therapy with curative potential. Overall, DHODH inhibition combined with temozolomde has clear therapeutic potential in neuroblastoma and we propose this combination as a candidate for clinical testing.

cancer biology↗

bioRxiv2020

Malignant Schwann cell precursors mediate intratumoral plasticity in human neuroblastoma

Neuroblastoma is a heterogeneous embryonal malignancy and the most deadly tumor of childhood, although a minor subset may show spontaneous differentiation. It arises from the multipotent neural crest lineage during development. Some of this multipotency is retained in neuroblastoma, which can give rise to both adrenergic and mesenchymal tumor cells. The mechanisms enabling such dual fates are unknown, but likely help neuroblastoma to evade existing therapies. To understand neuroblastoma plasticity, we analyzed patient tumors using single-cell transcriptomics. In addition to the heterogeneous adrenergic and mesenchymal populations, we identify a subpopulation of malignant cells resembling Schwann cell precursors (SCPs). This SCP-like population connects the adrenergic and mesenchymal compartments through transitions structurally reminiscent of the SCP cell-fate decision fork that occurs during normal development. While the directionality of such transitions in neuroblastoma remains to be established, this finding expands the potential reservoirs of malignant cells, and suggests intratumoral plasticity mechanisms relevant for therapeutic resistance and relapse.

cancer biology↗

bioRxiv2019

What is in a lichen? A metagenomic approach to reconstruct the holo-genome of Umbilicaria pustulata

Lichens are valuable models in symbiosis research and promising sources of biosynthetic genes for biotechnological applications. Most lichenized fungi grow slowly, resist aposymbiotic cultivation, and are generally poor candidates for experimentation. Obtaining contiguous, high quality genomes for such symbiotic communities is technically challenging. Here we present the first assembly of a lichen holo-genome from metagenomic whole genome shotgun data comprising both PacBio long reads and Illumina short reads. The nuclear genomes of the two primary components of the lichen symbiosis - the fungus Umbilicaria pustulata (33 Mbp) and the green alga Trebouxia sp. (53 Mbp) - were assembled at contiguities comparable to single-species assemblies. The analysis of the read coverage pattern revealed a relative cellular abundance of approximately 20:1 (fungus:alga). Gap-free, circular sequences for all organellar genomes were obtained. The community of lichen-associated bacteria is dominated by Acidobacteriaceae, and the two largest bacterial contigs belong to the genus Acidobacterium. Gene set analyses showed no evidence of horizontal gene transfer from algae or bacteria into the fungal genome. Our data suggest a lineage-specific loss of a putative gibberellin-20-oxidase in the fungus, a gene fusion in the fungal mitochondrion, and a relocation of an algal chloroplast gene to the algal nucleus. Major technical obstacles during reconstruction of the holo-genome were coverage differences among individual genomes surpassing three orders of magnitude. Moreover, we show that G/C-rich inverted repeats paired with non-random sequencing error in PacBio data can result in missing gene predictions. This likely poses a general problem for genome assemblies based on long reads.

genomics↗