Biology subjects

Moosa, M. M.

Publications and source records attributed to Moosa, M. M..

8 recordsLinked to original sources

bioRxiv2025

Functional and genomic insights into landfill-isolated Brucella intermedia strains capable of degrading Linear Low-Density Polyethylene (LLDPE)

The global accumulation of linear low-density polyethylene (LLDPE) waste has created an urgent need for sustainable biodegradation strategies. Here, we report the identification and characterization of two landfill-derived Brucella intermedia isolates associated with LLDPE biodegradation. Soil samples collected from the Matuail landfill in Dhaka, Bangladesh, were screened on minimal salt medium supplemented with LLDPE. Both isolates demonstrated sustained growth under carbon-limited conditions in which LLDPE was the principal carbon source. LLDPE recovered from bacterial cultures showed chemical and surface morphological changes, as supported by Fourier-transform infrared (FTIR) spectroscopy, droplet-spreading analysis, and scanning electron microscopy (SEM). FTIR analysis revealed additional carbonyl, hydroxyl, and C-O bands consistent with oxidative modification of the polymer surface, while SEM showed roughening, fissures, and fragmentation-like surface features. Whole-genome sequencing identified both isolates as closely related but distinct strains of Brucella intermedia and revealed enrichment of candidate functions associated with oxidative activation, depolymerization, and downstream assimilation. Transcriptomic analysis under LLDPE growth further showed expression of multiple candidate plastic degradation- and biofilm-associated genes. Resistome, virulome, and phenotypic antimicrobial susceptibility analyses indicated that both isolates are environmentally resilient, low-pathogenic variants with a limited intrinsic resistome. Both strains also exhibited biofilm-associated growth under hydrocarbon-substituted and plastic-associated conditions. Collectively, these findings identify environmental B. intermedia as an unexpected plastic-associated lineage and expand current understanding of the ecological and genomic diversity of bacteria linked to LLDPE biodegradation. Environmental ImplicationThis study identifies landfill-derived Brucella intermedia strains that can support biodegradation of linear low-density polyethylene (LLDPE), a major persistent plastic pollutant in landfill environments. Functional, genomic, and transcriptomic evidence indicate that these isolates use coordinated oxidative, depolymerization, and biofilm-associated responses during growth under plastic-associated, carbon-limited conditions. Their low-pathogenic environmental profiles and limited intrinsic resistomes further support their relevance as candidates for future biodegradation-focused biotechnological research. Overall, these findings expand the known diversity of plastic-associated bacteria and highlight naturally adapted landfill microorganisms as promising resources for sustainable strategies to mitigate plastic accumulation in terrestrial ecosystems. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/687417v2_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@5f84f2org.highwire.dtl.DTLVardef@111626dorg.highwire.dtl.DTLVardef@54f51eorg.highwire.dtl.DTLVardef@1a8910c_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

Heterotypic interactions in the dilute phase can drive co-condensation of prion-like low-complexity domains of FET proteins and mammalian SWI/SNF complex

Prion-like domains (PLDs) are low-complexity protein sequences enriched within nucleic acid-binding proteins including those involved in transcription and RNA processing. PLDs of FUS and EWSR1 play key roles in recruiting chromatin remodeler mammalian SWI/SNF complex to oncogenic FET fusion protein condensates. Here, we show that disordered low-complexity domains of multiple SWI/SNF subunits are prion-like with a strong propensity to undergo intracellular phase separation. These PLDs engage in sequence-specific heterotypic interactions with the PLD of FUS in the dilute phase at sub-saturation conditions, leading to the formation of PLD co-condensates. In the dense phase, homotypic and heterotypic PLD interactions are highly cooperative, resulting in the co-mixing of individual PLD phases and forming spatially homogeneous co-condensates. Heterotypic PLD-mediated positive cooperativity in protein-protein interaction networks is likely to play key roles in the co-phase separation of mSWI/SNF complex with transcription factors containing homologous low-complexity domains.

biophysics↗

bioRxiv2021

FUS Oncofusion Protein Condensates Recruit mSWI/SNF Chromatin Remodelers via Heterotypic Interactions Between Prion-like Domains

Fusion transcription factors generated by genomic translocations are common drivers of several types of cancers including sarcomas and leukemias. Oncofusions of the FET (FUS, EWSR1, and TAF15) family of proteins result from fusion of the prion-like domain (PLD) of FET proteins to the DNA-binding domain (DBD) of certain transcription regulators and are implicated in aberrant transcriptional programs through interactions with chromatin remodelers. Here, we show that FUS-DDIT3, a FET oncofusion protein, undergoes PLD-mediated phase separation into liquid-like condensates. Nuclear FUS-DDIT3 condensates can recruit essential components of the global transcriptional machinery such as the chromatin remodeler SWI/SNF. The recruitment of mammalian SWI/SNF is driven by heterotypic PLD-PLD interactions between FUS-DDIT3 and core subunits of SWI/SNF, such as the catalytic component BRG1. Further experiments with single-molecule correlative force-fluorescence microscopy support a model wherein the fusion protein forms condensates on DNA surface and enrich BRG1 to activate transcription by ectopic chromatin remodeling. Similar PLD-driven co-condensation of mSWI/SNF with transcription factors can be employed by other oncogenic fusion proteins with a generic PLD-DBD domain architecture for global transcriptional reprogramming.

biophysics↗

bioRxiv2021

Programmable Viscoelasticity in Protein-RNA Condensates with Disordered Sticker-Spacer Polypeptides

Liquid-liquid phase separation of multivalent proteins and RNAs drives the formation of biomolecular condensates that facilitate membrane-free compartmentalization of subcellular processes. With recent advances, it is becoming increasingly clear that biomolecular condensates are network fluids with time-dependent material properties. Here, employing microrheology with optical tweezers, we reveal molecular determinants that govern the viscoelastic behavior of condensates formed by multivalent Arg/Gly-rich sticker-spacer polypeptides and RNA. These condensates behave as Maxwell fluids with an elastically-dominant rheological response at shorter timescales and a liquid-like behavior at longer timescales. The viscous and elastic regimes of these condensates can be tuned by the polypeptide and RNA sequences as well as their mixture compositions. Our results establish a quantitative link between the sequence- and structure-encoded biomolecular interactions at the microscopic scale and the rheological properties of the resulting condensates at the mesoscale, enabling a route to systematically probe and rationally engineer biomolecular condensates with programmable mechanics.

biophysics↗

bioRxiv2020

Phase Transition of RNA-protein Complexes into Ordered Hollow Condensates

Liquid-liquid phase separation of multivalent intrinsically disordered protein-RNA complexes is ubiquitous in both natural and biomimetic systems. So far, isotropic liquid droplets are the most commonly observed topology of RNA-protein condensates in experiments and simulations. Here, by systematically studying the phase behavior of RNA-protein complexes across varied mixture compositions, we report a hollow vesicle-like condensate phase of nucleoprotein assemblies that is distinct from RNA-protein droplets. We show that these vesicular condensates are stable at specific mixture compositions and concentration regimes within the phase diagram and are formed through the phase separation of anisotropic protein-RNA complexes. Similar to membranes composed of amphiphilic lipids, these nucleoprotein-RNA vesicular membranes exhibit local ordering, size-dependent permeability, and selective encapsulation capacity without sacrificing their dynamic formation and dissolution in response to physicochemical stimuli. Our findings suggest that protein-RNA complexes can robustly create lipid-free vesicle-like enclosures by phase separation. Significance statementVesicular assemblies play crucial roles in subcellular organization as well as in biotechnological applications. Classically, the ability to form such assemblies were primarily assigned to lipids and lipid-like amphiphilic molecules. Here, we show that disordered RNA-protein complexes can form vesicle-like ordered assemblies at disproportionate mixture compositions. We also show that the ability to form vesicular assemblies is generic to multi-component systems where phase separation is driven by heterotypic interactions. We speculate that such vesicular assemblies play crucial roles in the formation of dynamic multi-layered subcellular membrane-less organelles and can be utilized to fabricate novel stimuli-responsive microscale systems.

biophysics↗

bioRxiv2019

Interplay Between Short-range Attraction and Long-range Repulsion Controls Reentrant Liquid Condensation of Ribonucleoprotein-RNA Complexes

In eukaryotic cells, ribonucleoproteins (RNPs) form mesoscale condensates by liquid-liquid phase separation that play essential roles in subcellular dynamic compartmentalization. The formation and dissolution of many RNP condensates are finely dependent on the RNA-to-RNP ratio, giving rise to a window-like phase separation behavior. This is commonly referred to as reentrant liquid condensation (RLC). Here, using RNP-inspired polypeptides with low-complexity RNA-binding sequences as well as the C-terminal disordered domain of the ribonucleoprotein FUS as model systems, we investigate the molecular driving forces underlying this non-monotonous phase transition. We show that an interplay between short-range cation-{pi} attractions and long-range electrostatic forces governs the heterotypic RLC of RNP-RNA complexes. Short-range attractions, which can be encoded by both polypeptide chain primary sequence and nucleic acid base sequence, are activated by RNP-RNA condensate formation. After activation, the short-range forces regulate material properties of polypeptide-RNA condensates and subsequently oppose their reentrant dissolution. In the presence of excess RNA, a competition between short-range attraction and long-range electrostatic repulsion drives the formation of a colloid-like cluster phase. With increasing short-range attraction, the fluid dynamics of the cluster phase is arrested, leading to the formation of a colloidal gel. Our results reveal that phase behavior, supramolecular organization, and material states of RNP-RNA assemblies are controlled by a dynamic interplay between molecular interactions at different length scales.

biophysics↗

bioRxiv2018

Molecular Crowding Tunes Material States of Ribonucleoprotein Condensates

Ribonucleoprotein (RNP) granules are membraneless liquid condensates that dynamically form, dissolve, and mature into a gel-like state in response to changing cellular environment. RNP condensation is largely governed by the promiscuous attractive inter-chain interactions, mediated by low-complexity domains (LCDs). Using an archetypal disordered RNP, Fused in Sarcoma (FUS), here we study how molecular crowding impacts the RNP liquid condensation. We observe that the liquid-liquid coexistence boundary of FUS is lowered by polymer crowders, consistent with the excluded volume model. With increasing bulk crowder concentration, RNP partition increases and the diffusion rate decreases in the condensed phase. Furthermore, we show that RNP condensates undergo substantial hardening wherein protein-dense droplets transition from viscous fluid to a viscoelastic gel-like state in a crowder concentration-dependent manner. Utilizing two distinct LCDs that broadly represent the most commonly occurring sequence motifs driving RNP phase transition, we reveal that the impact of crowding is largely independent of LCD charge/sequence patterns. These results are consistent with a thermodynamic model of crowder-mediated depletion interaction where inter-RNP attraction is enhanced by molecular crowding. The depletion force is likely to play key roles in tuning the physical properties of RNP condensates within a crowded intracellular space.

biophysics↗

bioRxiv2017

The N-terminal domain of ALS-linked TDP-43 assembles without misfolding

TDP-43 forms inclusions in several neurodegenerative diseases, and both its N- and C-terminal domains are implicated in this process. We show that the folded TDP-43 N-terminal domain oligomerizes under physiological conditions and propose that, in full-length TDP-43, association between folded N-terminal domains enhances the propensity of the intrinsically unfolded C-terminal domains to drive pathological aggregation.

biophysics↗