Biology subjects

Boros, E.

Publications and source records attributed to Boros, E..

5 recordsLinked to original sources

bioRxiv2025

Development of FAP-targeted theranostics discovered by next-generation sequencing-augmented mining of a novel immunized VNAR library

Cancer-associated fibroblasts (CAFs) in the stroma of solid tumors promote an immunosuppressive tumor microenvironment (TME) that drives resistance to therapies. The expression of the protease fibroblast activation protein (FAP) on the surface of CAFs has made FAP a target for development of therapies to dampen immunosuppression. Relatively few biologics have been developed for FAP and none have been developed that exploit the unique engagement properties of Variable New Antigen Receptors (VNARs) from shark antibodies. As the smallest binding domain in nature, VNARs cleverage unique geometries and recognize epitopes conventional antibodies cannot. By directly immunizing a nurse shark with FAP, we created a large anti-FAP VNAR phage display library. This library allowed us to identify a suite of anti-FAP VNARs through traditional biopanning and also by an in silico approach that did not require any prior affinity-based enrichment in vitro. We investigated four VNAR-Fc fusion proteins for theranostic properties and found that all four recognized FAP with high affinity and were rapidly internalized by FAP-positive cells. As a result, the VNAR-Fc constructs were effective antibody-drug conjugates in vitro and were able to localize to FAP-positive xenografts in vivo. Our findings establish VNAR-Fc constructs as a versatile platform for theranostic development that could yield innovative cancer therapies targeting the TME.

synthetic biology↗

bioRxiv2024

A matter of salt: global assessment of the effect of salt ionic composition as a driver of aquatic bacterial diversity

While the strong general effects of salinity on microbial diversity are well-known and described for marine and freshwater habitats, the impact of the specific composition of major inorganic ions remains largely unexplored. In this study, we assess how microbial community structure in inland saline aquatic habitats is influenced by ionic composition as compared to salinity, spatial factors, and other environmental parameters. We collected and analysed 16S rRNA gene V4 and V3-V4 amplicon datasets from freshwater to hypersaline aquatic environments worldwide (in total 375 samples from 130 lakes). With an emphasis on saline inland waters characterised by highly variable ionic composition, we demonstrated that the ionic composition of the major ions explained more variability in community composition than bulk salinity and that the geographic location of the sampling sites had only an ambiguous effect. We also identified the taxa contributing the most to the observed dissimilarity between communities from sites with different ionic composition and found mostly lineages known to be characteristic for a given habitat type, such as Actinobacteria acI in freshwater, Halomonadaceae in saline, or Nitriliruptorales in soda and soda-saline habitats. Many of these habitat type-specific indicator lineages were monophyletic, underpinning ionic composition as a crucial eco-evolutionary driver of aquatic microbial diversity.

microbiology↗

bioRxiv2021

Microbial stowaways - waterbirds as dispersal vectors of aquatic pro- and microeukaryotic communities

AimWaterbirds are important dispersal vectors of multicellular organisms such as macrophytes, aquatic macroinvertebrates, and zooplankton. However, no study to date has focused on their potential role in dispersing aquatic microbial communities (i.a., bacteria, algae, protozoa). Here, we explicitly studied passive transport (endozoochory) of prokaryotes and unicellular microeukaryotes by waterbirds based on DNA metabarcoding approaches. By directly comparing the dispersed set of organisms to the source pool of a natural metacommunity, we aimed for a realistic estimate of the overall importance of waterbird zoochory for natural microbial communities. LocationShallow saline temporary ponds (soda pans) in the cross-border region of Austria and Hungary. TaxonProkaryotes and unicellular microeukaryotes. MethodsIn 2017 and 2018, water samples from 25 natural aquatic habitats along with fresh droppings of the dominant greylag goose (Anser anser) and four other waterbird species were collected in a habitat network of temporary ponds. Their prokaryotic and microeukaryotic communities were identified via 16S and 18S rRNA gene amplicon sequencing. Sequence reads were analysed using mothur. After quality filtering of the reads, pro- and microeukaryotic amplicon sequencing variant (ASV) compositions were compared between the aquatic and dropping samples, across years and waterbird species. ResultsWe found that 28% of the dominant aquatic prokaryotic and 19% of the microeukaryotic ASVs were transported by A. anser. ASV richness in A. anser droppings was lower, but compositional variation was higher compared to the aquatic communities, probably resulting from stochastic pick-up of microbes from multiple aquatic habitats. We furthermore found that the composition of prokaryotic ASVs in bird droppings were different among the two years and reflected the actual aquatic communities. The dispersed set of microbes were largely similar among the different waterbird species except for the planktivore filter-feeder northern shoveler (Spatula clypeata) which was outstanding by dispersing a more species-rich subset of microeukaryotes than shorebirds or geese. Main conclusionsBy using a combined amplicon-sequencing approach to characterize microorganisms in waterbird droppings and in the associated environment, our study provides strong evidence for endozoochory of natural aquatic microorganism communities. These results imply that waterbirds may be crucial in maintaining ecological connectivity between discrete aquatic habitats at the level of microbial communities.

ecology↗

bioRxiv2020

Binding Profile Mapping of the S100 Protein Family Using a High-throughput Local Surface Mimetic Holdup Assay

S100 proteins are small, typically homodimeric, vertebrate-specific EF-hand proteins that establish Ca2+-dependent protein-protein interactions in the intra- and extracellular environment and are overexpressed in various pathologies. There are about 20 distinct human S100 proteins with numerous potential partner proteins. Here, we used a quantitative holdup assay to measure affinity profiles of most members of the S100 protein family against a library of chemically synthetized foldamers. The profiles allowed us to quantitatively map the binding promiscuity of each member towards the foldamer library. Since the library was designed to systematically contain most binary natural amino acid side chain combinations, the data also provide insight into the promiscuity of each S100 protein towards all potential naturally-occurring S100 partners in the human proteome. Such information will be precious for future drug design of modulators of S100 pathological activities.

biochemistry↗

bioRxiv2020

Grazing pressure-induced shift in planktonic bacterial communities with the dominance of acIII-A1 actinobacterial lineage in soda pans

Astatic soda pans of the Pannonian Steppe are unique environments with respect to their multiple extreme physical and chemical characteristics (high daily water temperature fluctuation, high turbidity, alkaline pH, salinity, polyhumic organic carbon concentration, hypertrophic state and special ionic composition). However, little is known about the seasonal dynamics of the bacterial communities inhabiting these lakes and the role of environmental factors that have the main impact on their structure. Therefore, two soda pans were sampled monthly between April 2013 and July 2014 to reveal changes in the planktonic community. By late spring in both years, a sudden shift in the community structure was observed, the previous algae-associated bacterial communities had collapsed, resulting the highest ratio of actinobacteria within the bacterioplankton (89%, with the dominance of acIII-A1 lineage) ever reported in the literature. Before these peaks, an extremely high abundance (>10,000 individuum l-1) of microcrustaceans (Moina and Arctodiaptomus) was observed. OTU-based statistical approaches showed that in addition to algal blooms and water-level fluctuations, zooplankton densities had the strongest effect on the composition of bacterial communities. In these extreme environments, this implies a surprisingly strong, community-shaping top-down role of microcrustacean grazers.

microbiology↗