Publications by authors named "Simona Bianco"

The design of supramolecular hydrogels comprising aligned domains is important for the fabrication of biomimetic materials and applications in optoelectronics. One way to access such materials is by the self-assembly of small molecules into long fibres, which can be aligned using an external stimulus. Out-of-equilibrium supramolecular gels can also be designed, where pre-programmed changes of state can be induced by the addition of chemical fuels.

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The spatial organization of chromatin within the eukaryotic nucleus is critical in regulating key cellular functions, such as gene expression, and its disruption can lead to disease. Advances in experimental techniques, such as Hi-C and microscopy, have significantly enhanced our understanding of chromatin's intricate and dynamic architecture, revealing complex patterns of interaction at multiple scales. Along with experimental methods, physics-based computational models, including polymer phase separation and loop-extrusion mechanisms, have been developed to explain chromatin structure in a principled manner.

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The dynamic three-dimensional (3D) organization of the human genome (the "4D Nucleome") is closely linked to genome function. Here, we integrate a wide variety of genomic data generated by the 4D Nucleome Project to provide a detailed view of human 3D genome organization in widely used embryonic stem cells (H1-hESCs) and immortalized fibroblasts (HFFc6). We provide extensive benchmarking of 3D genome mapping assays and integrate these diverse datasets to annotate spatial genomic features across scales.

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Understanding the function of a biomolecule hinges on its 3D conformation or secondary structure. Chirally sensitive, optically active techniques based on the differential absorption of UV-vis circularly polarized light excel at rapid characterisation of secondary structures. However, Raman spectroscopy, a powerful method for determining the structure of simple molecules, has limited capacity for structural analysis of biomolecules because of intrinsically weak optical activity, necessitating millimolar (mM) sample quantities.

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A long-standing challenge is how to formulate proteins and vaccines to retain function during storage and transport and to remove the burdens of cold-chain management. Any solution must be practical to use, with the protein being released or applied using clinically relevant triggers. Advanced biologic therapies are distributed cold, using substantial energy, limiting equitable distribution in low-resource countries and placing responsibility on the user for correct storage and handling.

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Midbrain dopamine neurons (DNs) respond to a first exposure to addictive drugs and play key roles in chronic drug usage. As the synaptic and transcriptional changes that follow an acute cocaine exposure are mostly resolved within a few days, the molecular changes that encode the long-term cellular memory of the exposure within DNs remain unknown. To investigate whether a single cocaine exposure induces long-term changes in the 3D genome structure of DNs, we applied Genome Architecture Mapping and single nucleus transcriptomic analyses in the mouse midbrain.

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SARS-CoV-2 can re-structure chromatin organization and alter the epigenomic landscape of the host genome, but the mechanisms that produce such changes remain unclear. Here, we use polymer physics to investigate how the chromatin of the host genome is re-organized upon infection with SARS-CoV-2. We show that re-structuring of A/B compartments can be explained by a re-modulation of intra-compartment homo-typic affinities, which leads to the weakening of A-A interactions and the enhancement of A-B mixing.

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Peptide-based biopolymers have gained increasing attention due to their versatile applications. A naphthalene dipeptide (2NapFF) can form chirality-dependent tubular micelles, leading to supramolecular gels. The precise molecular arrangement within these micelles and the mechanism governing gelation have remained enigmatic.

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Article Synopsis
  • Light can be utilized to create systems that respond to stimuli, like changes in their physical properties.
  • By using a specific type of photoacid called merocyanine, we can temporarily alter how a low molecular weight gel forms when exposed to light.
  • This method allows us to change the thickness (viscosity) of the gel on command, enabling precise control over its flow without any direct interference.
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SARS-CoV-2 is able to re-structure chromatin organization and alters the epigenomic landscape of the host genome, though the mechanisms that produce such changes are still poorly understood. Here, we investigate with polymer physics chromatin re-organization of the host genome, in space and time upon SARS-CoV-2 viral infection. We show that re-structuring of A/B compartments is well explained by a re-modulation of intra-compartment homotypic affinities, which leads to the weakening of A-A interactions and enhances A-B mixing.

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Extrachromosomal DNAs (ecDNAs) are found in the nucleus of an array of human cancer cells where they can form clusters that were associated to oncogene overexpression, as they carry genes and -regulatory elements. Yet, the mechanisms of aggregation and gene amplification beyond copy-number effects remain mostly unclear. Here, we investigate, at the single molecule level, -harboring ecDNAs of COLO320-DM colorectal cancer cells by use of a minimal polymer model of the interactions of ecDNA BRD4 binding sites and BRD4 molecules.

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Preparation of multicomponent systems provides a method for changing the properties of low molecular weight gelator (LMWG)-based systems. Here we have prepared a variety of multicomponent systems where both components are -functionalised dipeptide-based LMWGs that may either co-assemble or self-sort when mixed. We exemplify how varying the concentration ratio of the two components can be used to tune the properties of the multicomponent systems pre-gelation, during gelation and in the gel state using viscosity and rheology measurements, circular dichroism, NMR and small angle neutron scattering.

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Technology for measuring 3D genome topology is increasingly important for studying gene regulation, for genome assembly and for mapping of genome rearrangements. Hi-C and other ligation-based methods have become routine but have specific biases. Here, we develop multiplex-GAM, a faster and more affordable version of genome architecture mapping (GAM), a ligation-free technique that maps chromatin contacts genome-wide.

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Human chromosomes have a complex 3D spatial organization in the cell nucleus, which comprises a hierarchy of physical interactions across genomic scales. Such an architecture serves important functional roles, as genes and their regulators have to physically interact to control gene regulation. However, the molecular mechanisms underlying the formation of those contacts remain poorly understood.

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Background: Interest in point-of-care ultrasound (POCUS) and lung ultrasound (LUS) is growing in the nephrology and dialysis field, and the number of nephrologists skilled in what is proving to be the "5th pillar of bedside physical examination" is increasing. Patients on hemodialysis (HD) are at high risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) and developing coronavirus disease 2019 (COVID-19) serious complications. Despite this, to our knowledge there are no studies to date that show the role of LUS in this setting, while there are many in the emergency room, where LUS proved to be an important tool, providing risk stratification and guiding management strategies and resource allocation.

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Understanding the mechanisms underlying the complex 3D architecture of mammalian genomes poses, at a more fundamental level, the problem of how two or multiple genomic sites can establish physical contacts in the nucleus of the cells. Beyond stochastic and fleeting encounters related to the polymeric nature of chromatin, experiments have revealed specific, privileged patterns of interactions that suggest the existence of basic organizing principles of folding. In this review, we focus on two major and recently proposed physical processes of chromatin organization: loop-extrusion and polymer phase-separation, both supported by increasing experimental evidence.

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We use a pH-driven annealing process to convert between co-assembled and self-sorted networks in multicomponent gels. The initially formed gels at low pH are co-assembled, with the two components coexisting within the same self-assembled structures. We use an enzymatic approach to increase the pH, resulting in a gel-to-sol transition, followed by a hydrolysis to lower the pH once again.

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It is unclear how the length of a repetitive DNA tract determines the onset and progression of repeat expansion diseases, but the dynamics of secondary DNA structures formed by repeat sequences are believed to play an important role. It was recently shown that three-way DNA junctions containing slip-out hairpins of CAG or CTG repeats and contiguous triplet repeats in the adjacent duplex displayed single-molecule FRET (smFRET) dynamics that were ascribed to both local conformational motions and longer-range branch migration. Here we explore these so-called "mobile" slip-out structures through a detailed kinetic analysis of smFRET trajectories and coarse-grained modeling.

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Regulatory landscapes drive complex developmental gene expression, but it remains unclear how their integrity is maintained when incorporating novel genes and functions during evolution. Here, we investigated how a placental mammal-specific gene, Zfp42, emerged in an ancient vertebrate topologically associated domain (TAD) without adopting or disrupting the conserved expression of its gene, Fat1. In ESCs, physical TAD partitioning separates Zfp42 and Fat1 with distinct local enhancers that drive their independent expression.

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Article Synopsis
  • - The study compares loop-extrusion and phase-separation as mechanisms for shaping chromosome organization, evaluating their effectiveness individually and together in terms of chromatin structure.
  • - Through the analysis of multiplexed FISH data in human cell lines, both mechanisms demonstrated a strong fit with bulk Hi-C and single-molecule chromatin conformations, especially showing the impact of phase-separation.
  • - The findings suggest that combining loop-extrusion with phase-separation models effectively explains chromatin architecture, highlighting that these mechanisms can work together in single cells while accounting for variability due to epigenetic differences and thermodynamic factors.
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Within cell nuclei, several biophysical processes occur in order to allow the correct activities of the genome such as transcription and gene regulation. To quantitatively investigate such processes, polymer physics models have been developed to unveil the molecular mechanisms underlying genome functions. Among these, phase-separation plays a key role since it controls gene activity and shapes chromatin spatial structure.

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The COVID-19 pandemic has caused millions of infections and deaths so far. After recovery, the possibility of reinfection has been reported. Patients on hemodialysis are at high risk of contracting SARS-CoV-2 and developing serious complications.

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The mammalian genome has a complex, functional 3D organization. However, it remains largely unknown how DNA contacts are orchestrated by chromatin organizers. Here, we infer from only Hi-C the cell-type-specific arrangement of DNA binding sites sufficient to recapitulate, through polymer physics, contact patterns genome wide.

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The X-linked gene encoding aristaless-related homeobox () is a bi-functional transcription factor capable of activating or repressing gene transcription, whose mutations have been found in a wide spectrum of neurodevelopmental disorders (NDDs); these include cortical malformations, paediatric epilepsy, intellectual disability (ID) and autism. In addition to point mutations, duplications of the locus have been detected in male patients with ID. These rearrangements include telencephalon ultraconserved enhancers, whose structural alterations can interfere with the control of expression in the developing brain.

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Supramolecular gels can be designed such that pre-determined changes in state occur. For example, systems that go from a solution (sol) state to a gel state and then back to a sol state can be prepared using chemical processes to control the onset and duration of each change of state. Based on this, more complex systems such as gel-to-sol-to-gel and gel-to-gel-to-gel systems can be designed.

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