Biology subjects

Blazquez, S.

Publications and source records attributed to Blazquez, S..

3 recordsLinked to original sources

bioRxiv2026

A DNA deliverer-receiver mechanism for DNA recruitment in phase-separated transcriptional condensates

DNA transcription is a complex process involving numerous components that can assemble into phase-separated transcriptional condensates. However, whether condensates formed by multiple transcription factors behave through simple additive effects or instead exhibit non-additive, emergent properties remains unclear. Here, we use large-scale molecular dynamics simulations to investigate how three core transcription factors regulating pluripotency and early embryonic development--Nanog, Oct4, and Sox2--organize biomolecular condensates in the absence and presence of DNA. We find that condensate formation is primarily driven by intrinsically-disordered-region-mediated interactions of Nanog and Sox2, each of which individually promotes Oct4 phase separation; by contrast, when Nanog and Sox2 coexist in the absence of DNA, Oct4 is less efficiently incorporated into condensates. In the presence of DNA, condensates display a distinct spatial organization: Nanog and Sox2 form dense, well-mixed clusters, whereas Oct4 remains more dispersed in interstitial regions where DNA preferentially localizes, resulting in [~]20% higher DNA content in Oct4-containing condensates. Notably, phase separation reshapes DNA-protein interaction landscapes, altering the intramolecular regions that engage DNA. Together, these results support a synergistic DNA deliverer-receiver mechanism and suggest that non-additive, multi-component condensate organization constitutes an additional layer of gene expression regulation beyond canonical transcription factor-DNA binding.

biophysics↗

bioRxiv2026

Micropollutant-driven bacterial adaptation enables resilient pharmaceuticals biodegradation at trace concentrations in biologically treated wastewater.

Pharmaceutical residues are persistent contaminants that resist conventional wastewater treatment and can disrupt ecosystems; however, microorganisms provide a promising biobased solution to transform or mineralize these complex xenobiotics. Whether pollutant-adapted communities maintain their degradative capacity under realistic environmental conditions remains a long-standing debate in environmental biotechnology. Here, microbial consortia enriched in six membrane bioreactors under high pharmaceutical concentration (100 mg/L) retained full biodegradation capacity across a 5000-fold concentration range. After prolonged exposure to six model compounds (atenolol, caffeine, diclofenac, enalapril, ibuprofen, and paracetamol) complete removal occurred for all except diclofenac. Degradation remained efficient even at lower and environmentally relevant concentrations (1 mg/L-20 {micro}g/L) and recovered rapidly upon re-exposure to higher loads (100 mg/L). Metagenomic profiling revealed enrichment of oxygenase-mediated catabolic pathways supporting this resilience. When transferred to a 7 liters bioreactor treating real wastewater, the adapted community removed targeted and untargeted pharmaceuticals, demonstrating robustness, scalability, and strong potential for sustainable micropollutant remediation. Environmental ImplicationPharmaceuticals and their metabolites are environmentally hazardous because these bioactive micropollutants are persistent and continuously discharged via wastewater, thereby endangering both ecosystem and human health. This study shows that pollutant-adapted microbial consortia can address this challenge, retaining strong degradative function across large concentration fluctuations, including environmentally relevant levels. It also demonstrates scalability: the adapted community can be transferred to real-wastewater operation to remove both targeted and additional pharmaceuticals, supporting a bio-based "polishing" step for wastewater treatment plants. Overall, these findings support more sustainable biological mitigation strategies to reduce micropollutant loads.

microbiology↗

bioRxiv2022

Reordering of aromatic-rich segments in FUS inhibits ageing of FUS-RNA condensates

Maturation of functional liquid-like biomolecular condensates into solid-like aggregates has been linked to the onset of several neurodegenerative disorders. Low-complexity aromatic-rich kinked segments (LARKS) contained in numerous RNA-binding proteins can promote aggregation by forming inter-protein {beta}-sheet fibrils that accumulate over time and ultimately drive the liquid-to-solid transition of the condensates. Here, we combine atomistic molecular dynamics simulations with sequence-dependent coarse-grained models of various resolutions to investigate the role of LARKS abundance and position within the amino acid sequence in the maturation of condensates. Remarkably, proteins with tail-located LARKS display much higher viscosity over time than those in which the LARKS are placed towards the center. Yet, at very long timescales, proteins with a single LARKS--independently of its location--can still relax and behave as high viscous liquids. However, phase-separated condensates of proteins containing two or more LARKS become kinetically trapped due to the formation of percolated {beta}-sheet networks that display gel-like behaviour. Furthermore, as a work case example, we demonstrate how shifting the location of the LARKS-containing low-complexity domain of FUS protein towards its center effectively precludes the accumulation of {beta}-sheet fibrils in FUS-RNA condensates, maintaining functional liquid-like behaviour without ageing.

biophysics↗