Project description:Whole genome sequencing of SYBARIS Aspergillus spp. known to be multi-drug resistant and difficult to treat. Aim of this experiment is to investigate the genetic basis of susceptibility to disease and elucidate molecular mechanisms of drug resistance in these strains.
Project description:Emergomyces africanus is a thermally dimorphic fungus and one of the leading causes of emergomycosis, a neglected infection primarily affecting immunocompromised individuals. Despite its clinical relevance, how E. africanus adapts to the host environment remains unknown. Recent studies suggest that extracellular vesicles (EVs) may play a key role during host adaptation by modulating immune responses and transporting virulence factors. It remains unknown whether E. africanus produces EVs. Here, we demonstrated EV production in E. africanus and investigated their size and composition after cultivation in nutrient-rich and nutrient-limited media, mimicking environmental and host-like conditions. In addition, we evaluated the effect of E. africanus EVs released in nutrient-limited media on bone marrow-derived dendritic cells (BMDCs) and bone marrow-derived macrophages (BMDMs). Under nutrient limitation, E. africanus released EVs enriched in proteins that, in other models, are virulence-associated, including catalase, HSP60, and chitinase, whereas EVs from rich media carried proteins linked to anabolic pathways. The presence of -1,3-glucans and a higher content of chitin-like structures were also detected in EVs released in nutrient-limited conditions. EVs from nutrient-limited conditions activated BMDCs, increasing MHC-II and CD40 expression and promoting a pro-inflammatory cytokine profile (IL-6 and TNF-α). In contrast, BMDMs exhibited elevated IL-10 levels, suggesting an anti-inflammatory shift. Remarkably, EV pre-treatment enhanced BMDM antifungal activity, significantly reducing E. africanus viability post-infection. These findings show that E. africanus dynamically adjust their EVs cargo in response to environmental cues, directly influencing immune modulation and fungal survival. Indeed, pre-treatment of the insect Galleria mellonella with these EVs induced a protective response against a lethal inoculum of Histoplasma capsulatum. This study reinforces the potential of EVs as therapeutic targets and offers new insights into how E. africanus adapts to the host environment.
Project description:Primary objectives: The primary objective is to investigate circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Primary endpoints: circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Project description:One ONT-ULK sequencing run from the kidney of a single male CDMR (Bathyergus suillus) sample used to make the mBatSui1.1.primary genome assembly as an evolutionary comparator to our telomere-to-telomere naked mole-rat genome assembly. Specifically, we assembled a CDMR from a wild-derived sample in South African cape and sequenced in Toronto, Canada, using PacBio HiFi (89 Gb, read N50 = 18 Kb) and ONT-ULK (55 Gb, read N50 = 43 Kb) reads (contig N50 = 33 Mb, Compleasm S = 99%, QV = 71.0). This accession stores the ONT-ULK data for this assembly.
Project description:One PacBio Hifi sequencing run from the kidney of a single male CDMR (Bathyergus suillus) sample used to make the mBatSui1.1.primary genome assembly as an evolutionary comparator to our telomere-to-telomere naked mole-rat genome assembly. Specifically, we assembled a CDMR from a wild-derived sample in South African cape and sequenced in Toronto, Canada, using PacBio HiFi (89 Gb, read N50 = 18 Kb) and ONT-ULK (55 Gb, read N50 = 43 Kb) reads (contig N50 = 33 Mb, Compleasm S = 99%, QV = 71.0). This accession stores the Pacbio Hifi data for this assembly.
