Biology subjects

Bicker, A.

Publications and source records attributed to Bicker, A..

3 recordsLinked to original sources

bioRxiv2023

Adaptation of the Spalax galili transcriptome to life under hypoxia may hold a key to a complex phenotype including longevity and cancer resistance

The muroid rodent Nannospalax galili (syn. Spalax) is adapted to life in underground burrows and tolerates acute exposure to severe hypoxia. Adaptation to hypoxia is correlated with delayed onset of ageing and resistance against tumour formation. Spalax becomes five to seven times older than its relatives, the mouse and rat, without displaying signs of ageing or developing ageing-related disorders like cancer. Investigating and understanding adapted genes and gene regulatory networks of Spalax might pinpoint novel strategies to maintain an extended healthy phenotype in humans. Here we analysed and compared RNA-Seq data of liver, kidney and spleen of Spalax and rat subjected to 6% O2 or normoxia. We identified differentially expressed genes and pathways common to multiple organs in Spalax and rat. Body-wide differences between Spalax and rat affected biological processes like cell death, defence against reactive oxygen species (ROS), DNA repair, energy metabolism, immune response and angiogenesis, which altogether might play a crucial role in Spalaxs adaptation to life under oxygen deprivation. In all organs, mRNA expression of genes associated with genome stability maintenance and DNA repair was elevated in Spalax compared to rat, accompanied by a lower gene expression of genes associated with aerobic energy metabolism and proinflammatory processes. These transcriptomic changes might be accountable for the extraordinary lifespan of Spalax and its cancer resistance. Our results reveal gene regulatory networks that become candidates for the investigation of the molecular bases that underlie the complex phenotype of Spalax.

evolutionary biology↗

bioRxiv2022

Pro-apoptotic and anti-invasive properties underscore the tumor suppressing impact of myoglobin on subset of human breast cancer cells

Expression of myoglobin (MB), well known as the oxygen storage and transport protein of myocytes, is a novel hallmark of the luminal subtype in breast cancer patients and correlates with better prognosis. The mechanisms by which MB impacts mammary tumorigenesis are hitherto unclear. We aimed to unravel this role, by using CRISPR/Cas9 technology to generate MB-deficient clones of MCF7 and SKBR3 breast cancer cell lines and subsequently characterize them by transcriptomics plus molecular and functional analyses. As main findings, loss of MB, at normoxia, upregulated the expression of cell cyclins and increased cell survival while it prevented apoptosis in MCF7 cells. Also, MB-deficient cells were less sensitive to doxorubicin but not ionizing radiation. Under hypoxia, loss of MB enhanced partial epithelial to mesenchymal transition, thus augmenting the migratory and invasive cell behavior. Notably, in human invasive mammary ductal carcinoma tissues, MB and apoptotic marker levels were positively correlated. In addition, MB protein expression in invasive ductal carcinomas was associated with a positive prognostic value, independent of the known tumor suppressor p53. In conclusion, we provide multiple lines of evidence that endogenous MB in cancer cells by itself exerts novel tumor-suppressive roles through which it can reduce cancer malignancy.

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↗