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DTSTART;TZID=Europe/Madrid:20220527T100000
DTEND;TZID=Europe/Madrid:20220527T120000
DTSTAMP:20260502T121524
CREATED:20220503T132210Z
LAST-MODIFIED:20220503T132210Z
UID:91656-1653645600-1653652800@ibecbarcelona.eu
SUMMARY:PhD Discussions: Srivatsava Viswanadha Venkata Naga Sai and Madhura Murar
DESCRIPTION:Mechanical characterization of murine pluripotency dissolution\nSrivatsava Viswanadha Venkata Naga Sai\, Cellular and Molecular Mechanobiology Group \nMouse Embryonic Stem Cells (mESCs) can be maintained in ground/naïve state when grown in a defined N2B27 media with the supplementation of two inhibitors (2i) for MEK/Erk and GSK3β. Upon 2i withdrawal\, mESCs exit naïve state and become functionally mature\, acquiring differentiation competence. From a mechanical point of view\, the instruction for initiating ground state exit is the integrin mediated mechano-sensing of extra cellular matrix (ECM). Although laminin has been found to be the pivotal ECM ligand for pluripotency dissolution\, the down-stream mechano-responses accompanying its sensing\, their spatio-temporal evolution and\, their regulatory role in mESC maturation remain unclear. In this work\, we combine mechanical measurements\, functional characterization\, and live cell imaging to unravel the role of mESCs-ECM interactions during naïve state exit and pluripotency dissolution. We employ a Rex1::GFPd2 expressing mESC line to monitor naïve state exit in real time\, combined with a laminin-rich ECM environment. During naïve state exit\, we observe a progressive increase in cell-ECM interaction\, marked by an increase in traction forces\, growth of focal adhesions\, and the reorganization of the basal actin from a mesh-like network into an oriented filamentous morphology reminiscent of stress fibres. Furthermore\, inhibition of non-muscle myosin-II using blebbistatin significantly delayed naïve state exit\, suggesting a regulatory role of cell contractility in mESC maturation. We finally investigate the role of these changes in cell-ECM interactions in mediating nuclear mechanoresponses\, and their influence in mESC pluripotency dissolution. \n\n\nDual peptide-mediated design of polymeric nanoparticles: towards precision prostate cancer targeting\nMadhura Murar\, Nanoscopy for Nanomedicine Group \nA key bottleneck of current cancer treatments is the lack of selective targeting of cancer cells to reduce undesirable side-effects. Nanoparticles (NPs) allow for the design of ligand-coated materials that can fulfil this function but have not yet shown consistent clinical results to make the ‘magic bullet’ theory a paradigm. The inconsistencies may be due to a range of biological factors like differences in disease models or expression levels of target receptor(s). NP design parameters could play a key role in alleviating these inconsistencies and significantly influence the therapeutic efficacy. To further improve this efficacy\, multi-ligand targeting strategies have been proposed\, however\, they remain controversial as they involve an intricate interplay between multitude of factors such as choice of ligands\, their receptor binding affinities\, NP surface densities\, stoichiometric ratios etc.\, thereby calling for a thorough understanding of the impact of these properties to improve their targeting potential. \nWithin this context\, we employ two cell targeting peptides (WQP and GE11) having different binding affinities to PSMA and EGFR receptors\, which are known PCa biomarkers. We evaluate the effect of multivalency of low affinity WQP peptide over its monomeric form on PSMA targeting. We find that by increasing the valency of WQP on NP surface\, we observe a higher cellular uptake of WQP-NPs over the monomeric form\, attributing to a stronger avidity. Next\, we assess the effect of two conjugation strategies using the high affinity GE11 peptide and study their impact on EGFR targeting in a systematic manner. We observe that conjugating GE11 peptide to PLGA-PEG polymer prior to NP formulation (pre-conjugation) allows for a higher and more controlled GE11 content on NP surface than conjugating it to formulated PLGA-PEG NPs (post-conjugation)\, consequently leading to a higher cellular uptake. \nBased on these findings\, we report a synthetic strategy for dual peptide-NPs with systematically varied properties\, specifically surface valencies and ratios\, and establish their impact on selective targeting in a prostate cancer (PCa) model. First\, we study the impact of peptide valencies on NP surface of dual NPs in comparison to single peptide-NPs on the selective cellular uptake in different PCa cell lines. Once we establish optimal surface valency\, we check the effect of different surface peptide ratios on cellular uptake and determine the optimal ratio for enhanced targeting of only those cells over-expressing both receptors\, by the virtue of improved selectivity. Somewhat counterintuitively\, we observe an increase in tumor cell uptake of NPs with lower peptide density\, which can be attributed to improved surface distribution of the peptide\, allowing for an enhanced availability to react with target receptor. This increase in uptake is a result of the two peptides acting in co-operation\, as opposed to simply an additive effect. Our findings demonstrate that through refined design and well-characterized NP formulations\, dual-peptide targeted nanosystems hold potential to provide precise cancer treatments. \n  \nThis PhD Discussion session will be held at Tower I\, 11th floor Baobab room\, at 10:00am.
URL:https://ibecbarcelona.eu/event/phd-discussion/
LOCATION:IBEC\, floor 11\, Tower I\, Baldiri Reixac 4-8\, 08028 Barcelona\, Spain
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20220715T100000
DTEND;TZID=Europe/Madrid:20220715T120000
DTSTAMP:20260502T121524
CREATED:20220503T132602Z
LAST-MODIFIED:20220503T132602Z
UID:96603-1657879200-1657886400@ibecbarcelona.eu
SUMMARY:PhD Discussions: Marc Azagra and Inês Sousa
DESCRIPTION:Novel Nuclear Magnetic Resonance (NMR) applications in the clinical field\nMarc Azagra\, Molecular Imaging for Precision Medicine Group \nWhen nuclear magnetic resonance (NMR) was described more than half a century ago it appeared to be a curiosity of the quantum world. Since then NMR spectroscopy has become an essential tool not only for chemists\, but also for biochemists\, molecular biologists and even clinicians. Today we are going to explain what is Hyperpolarization NMR\, main differences with thermal NMR acquisitions and two of the projects I am involved with: a new NMR application in clinical diagnosis stage for Liver disease and the first experiment ever performed with High-throughput Hyperpolarized Magnetic Resonance Imaging experiment with a multiwell microfluidic chips using Chemical Shift Imaging (CSI) pulse sequence. \n\n\nVersatile gelatine-based biomaterials compatible with neuronal differentiation: Applications in different systems for brain modelling\nInês Sousa Pereira\, Nanobioengineering Group \nTissue engineering has been focused on recreating the tissue environment of many organs\, such as the brain\, for modelling and for therapeutic approaches during the last years. Recently\, 3D brain in vitro models have been explored as they resemble more accurately physiological conditions of this organ. However\, neuronal cultures are challenging due to the high sensitivity of these cells to changes in their surroundings. \nWe present a hydrogel composed of methacrylated gelatine (GeIMA)\, alginate (AlgMA) and hyaluronic acid (HA) for neural progenitor cell culture in this work. Our goal was to assess the compatibility of GelMA and AlgMA composites with neuronal culture as these two materials are common in tissue engineering applications. HA was added to better mimic the stiffness of the brain tissue. Neuroprogenitor mouse cell line C17.2 was embedded in the gelatine-based formulations and cultured as 3D scaffold in a drop shape or inserted in a microfluidic device. They were also used as bioinks for extrusion bioprinting. We performed the physical characterization of both formulations\, viability studies\, immunostainings to assess the differentiation process and calcium imaging to validate the activity of the cells. \nResults show that hydrogels with and without hyaluronic acid have good porosity\, allowing nutrient and oxygen diffusion. They also present low Young Modulus\, especially for hyaluronic acid formulation\, rendering values similar to the brain tissue.\, the viability of the cells as well as the cell differentiation and connectivity were high after 28 days in culture In the assays with the formulations as scaffolds. The activity of the cells was assessed at day 8 and increased by day 15 for both formulations\, showing that cells were differentiating\, and the neuronal network was maturating. In the bioprinting assays\, the formulations presented high cell viability up to 15 days after printing and day 15 immunostaining showed the expression of neuroprogenitor marker nestin and early neuron marker β-III tubulin. On 3D-brain on the chip assays\, the both formulations had high cell viability up until day 15 of culture\, increasing expression of β-III tubulin as well as cell activity. \nIn conclusion\, our formulations allow long-term cell culture\, including high expression of neuronal markers\, cell connectivity and activity and the presence of HA gave the hydrogel physical characteristics closer to brain tissue while permitting a high cell viability and allowing the differentiation of C17.2 cells. These biomaterials are also suitable as bioinks for extrusion in a bioprinter as proven by the good viability of the cells and the compatibility with the differentiation process. The formulations were also tested in a microfluidic system\, maintaining the viability\, differentiation\, and activity capacities of the cells. Overall\, these results make these hydrogels a promising scaffold for brain modelling\, applicable to 3D long-term culture and differentiation of cells\, such as iPSC-derived neurons. \n  \nThis PhD Discussion session will be held at Tower I\, 11th floor Baobab room\, at 10:00am.
URL:https://ibecbarcelona.eu/event/phd-discussions/
LOCATION:IBEC\, floor 11\, Tower I\, Baldiri Reixac 4-8\, 08028 Barcelona\, Spain
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20230203T100000
DTEND;TZID=Europe/Madrid:20230203T130000
DTSTAMP:20260502T121524
CREATED:20230126T085229Z
LAST-MODIFIED:20230126T085229Z
UID:103689-1675418400-1675429200@ibecbarcelona.eu
SUMMARY:PhD Discussions: Gerardo Ceada Torres
DESCRIPTION:Role of Eph/Ephrin in the Compartmentalization of the Intestinal Stem Cell Niche\nGerardo Ceada Torres\, Integrative cell and tissue dynamics Group \nThe intestinal epithelium is a monolayer of cells that covers the inner surface of the gut. It protects against pathogens\, absorbs nutrients\, and secretes hormones and other molecules. This monolayer is folded into finger-like protrusions composed of differentiated cells\, called villi\, and invaginations\, called crypts\, where stem cells reside. Essential features of the intestinal epithelium such as folding of the crypt\, spatial distribution of different cell types\, and cellular movements from crypt to villus-like domains can be recapitulated in vitro in intestinal organoids. Direct force measurements in mouse intestinal organoids grown on soft hydrogels show that tightly regulated cell-ECM and cell-cell forces compartmentalizes the tissue into crypts- and villus-like domains. A dynamic mechanical boundary composed of basally constricted cells is established between the stem cell niche and differentiated cells of the villus-like region. The Eph/Ephrin signaling pathway has been proposed as a key regulator of compartmentalization and cell positioning in the intestinal epithelium. Whether and how Eph/Ephrin signaling governs the mechanical phenotype observed at the crypt-villus boundary remains\, however\, an open question. We are currently addressing this question by genetically perturbing Eph/Ephrin signaling in intestinal organoids. Preliminary data show that EphB2/3 KO organoids display defects in cell positioning\, reduced basal constriction at the crypt-villus boundary and aberrant size of the proliferative and differentiated compartments. \n\n  \n  \nThis PhD Discussion session will be held at Tower I\, 11th floor Baobab room\, at 10:00am.
URL:https://ibecbarcelona.eu/event/phd-discussions-gerardo-ceada-torres/
LOCATION:Sala Dolors Aleu\, Cluster II\, IBEC\, Baldiri i Reixac\, Barcelona
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20230331T100000
DTEND;TZID=Europe/Madrid:20230331T110000
DTSTAMP:20260502T121524
CREATED:20230322T104147Z
LAST-MODIFIED:20230322T111957Z
UID:106348-1680256800-1680260400@ibecbarcelona.eu
SUMMARY:PhD Discussions: José Muñoz-López
DESCRIPTION:Design and characterization of bifunctional hydrophilic Janus micelles\nJosé Muñoz-López\, Molecular Bionics Group \nJanus micelles are featured by their biphasic geometry of heterogeneous composition and distinctive properties in the core and corona. Such anisotropic design has attracted much attention from the scientific community due to the versatility of chemistries employed for generating Janus’ morphologies and their potential applications. In this work\, we present a novel ABC amphiphilic triblock copolymer system with the ability to form Janus micelles. The micelles are generated by solution-mediated self-assembly of the A and C hydrophilic\, and B hydrophobic blocks. Subsequently\, the hydrophilic blocks in the proposed triblock system will be functionalized with different and specific bioactive ligands to enable the constitution of multifunctional supramolecular scaffolds. The final aim of the project herein presented is to develop nanodrugs with well-defined dissimilar phenotypical domains\, in the same fashion as the asymmetric functionalisation of antibodies that already exist in nature\, to perform alike. To this end\, poly(ethylene glycol)-polylactide-poly(N-vinylpyrrolidone) PEG-PLA-PVP triblock copolymer was synthesised in two steps: first\, poly(ethylene glycol)-polylactide-2-bromo-2-methylpropanoate (PEG-PLA-Br) diblock macroinitiator was synthesized by the ring-opening polymerization of DL-lactide with commercial poly(ethylene glycol) and quenched with 2-bromo-isobutiryl-bromide. After that triblock copolymer was synthesized by the atom transfer radical polymerization (ATRP) of N-vinylpyrrolidone monomer (NVP) initiated by the PEG-PLA-Br diblock produced in the former synthetic step. The characterization of the produced diblock and triblock copolymers were carried out by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). Such techniques enabled us to verify the controlled radical polymerization of NVP and the complete conversion of PEG-PLA-Br diblock to the proposed PEG-PLA-PVP triblock. The morphologies adopted by PEG-PLA-Br and PEG-PLA-PVP in solution were investigated by transmission electron microscopy (TEM)\, confirming the formation of micelles for both block copolymers. TEM images showed differences in the negative stained micelles generated in the diblock and triblock copolymers systems. Such differences indicate the asymmetric distribution of both hydrophilic blocks\, PEG and PVP\, in the self-assembling of the PEG-PLA-PVP triblock system. Further structure characterizations will include atomic force microscopy (AFM)\, cryo-TEM\, electron energy loss spectroscopy (EELS)\, and ultimately the functionalization of both coronas with different targeting ligands. \n\n  \nThis PhD Discussion session will be held at Tower I\, 11th floor Baobab room\, at 10:00am.
URL:https://ibecbarcelona.eu/event/phd-discussions-jose-munoz-lopez/
LOCATION:Sala Dolors Aleu\, Cluster II\, IBEC\, Baldiri i Reixac\, Barcelona
CATEGORIES:PhD Discussions Session
ORGANIZER;CN="IBEC":MAILTO:www.ibecbarcelona.eu
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20230428T100000
DTEND;TZID=Europe/Madrid:20230428T110000
DTSTAMP:20260502T121524
CREATED:20230420T113916Z
LAST-MODIFIED:20250306T162535Z
UID:107325-1682676000-1682679600@ibecbarcelona.eu
SUMMARY:PhD Discussions: Ainoa Tejedera and Zarina Nauryzgaliyeva
DESCRIPTION:Mimicking Sarcolemmal Damage In vitro: A 3D Skeletal Muscle Model for Drug Testing in Duchenne Muscular Dystrophy\nAinoa Tejedera Villafranca\, Biosensors for bioengineering group \nDuchenne muscular dystrophy (DMD) is the most prevalent neuromuscular disease diagnosed in childhood. It is a progressive and wasting disease\, characterized by a degeneration of skeletal and cardiac muscles caused by the lack of dystrophin protein. The absence of this structural protein leads to the fragility of the sarcolemma\, and muscle fibers are damaged during their contraction. To date\, there is no cure available for patients\, even though there are several molecules in drug development. However\, due to the well-known limitations of preclinical research\, the success rate of drugs remains low. In this work\, intending to accelerate drug discovery for DMD\, we developed a patient-derived functional 3D model of DMD. By using a 3D-printed casting mold\, we encapsulated muscle progenitor cells in a fibrin-composite matrix. This platform incorporates two flexible T-shaped pillars that serve as anchoring points and provide continuous tension to the tissue\, thus allowing the orientation of the muscle fibers. The skeletal muscle tissues expressed mature myogenic markers and showed functional phenotypes as they responded to electrical pulse stimulation (EPS) by contracting. We observed that DMD muscle tissues\, after continuous contractile regimes\, reproduced the loss of myotube integrity that is observed in dystrophinopathies due to the sarcolemmal instability. DMD but not healthy tissues showed functional phenotypes caused by the induced sarcolemmal damage\, such as tetanic fatigue. Finally\, the applicability of this DMD model in evaluating therapeutic compounds was explored. Specifically\, we investigate the effect of utrophin up-regulators on functional outcomes of the model\, thus identifying potential candidates for the treatment of DMD. Taking all these considerations together\, our results show that bioengineered 3D skeletal muscle technology has great potential to be especially valuable in the context of current and future discovery and development of drugs to treat DMD and other neuromuscular disorders. \n\nDissecting early nephron patterning and segmentation in kidney organoids derived from hPSCs\nZarina Nauryzgaliyeva \, Pluripotency for organ regeneration Group \nThe formation and maturation of organs during development is a complex\, yet beautifully orchestrated process. Embryonic cells have a unique capacity to self-organize within the forming tissue\, where morphogenetic movements have been shown to facilitate tissue organization and subsequent organ formation. In kidney organogenesis\, the mature organ arises from crucial reciprocal interactions between the ureteric bud (UB) and metanephric mesenchyme (MM)\, which give rise to the collecting duct and nephron\, respectively. The development of mature nephrons during kidney organogenesis is a dynamic process so far studied taking advantage of in vivo models. Accumalative findings in mice have shown that the MM undergoes mesenchymal to epithelial transition (MET)\, giving rise to epithelial renal vesicles (RVs) that further undergo structural changes and shift towards comma shaped and s-shaped bodies (CSBs/SSBs)\, which eventually develop into nephron like structures. Those studies have helped identify Wnt/b-catenin and Notch signalling pathways as key players in nephron patterning and segmentation (proximal\, medial\, distal segments).\nAt the same time\, tissue morphogenesis is largely a biomechanical process\, resulting from constant movements of cells\, changes in forms of developing segments and forces generated therein. The biomechanical dynamics occurring during RV emergence and further nephron patterning are yet to be explored in the human context in real time. If these biomechanical processes are interconnected with mechanical signals remains an open question in the field. The answer to these questions may have an important impact for understanding nephron formation\, and conversely\, disease-related phenotypes due to mutations in genes orchestrating RV patterning and segmentation as occurs in congenital defects of the kidney and the urinary tract (CAKUT disease).\nHere\, we aim to use human pluripotent stem cell (hPSCs) derived kidney organoids to gain fundamental understanding of early nephron patterning and segmentation by mapping force transmission between cells and their extracellular matrix (ECM) and evaluating their co-evolution during renal fate specification and differentiation.\nhPSCs are guided towards the renal fate on compliant PDMS hydrogels with controlled rigidities (mimicking embryonic microenvironment) in a 2D culture system. PDMS hydrogels between 3 kPa (soft) and 18 kPa (rigid) are generated by adapting the compositional ratio of PDMS components and are further functionalized and decorated with fibronectin. Using this system\, we have started to spatiotemporally characterise early steps of nephrogenesis by immunofluorescence and confocal analysis\, time-lapse imaging\, and traction force microscopy (TFM). These analyses are nowadays conducted during RV emergence prior proximal-distal RV polarization and formation of the nephron-like segments.\nThe current techniques will permit quantitative and qualitative observations of multicellular behaviours at key stages of 2D renal differentiation. Furthermore\, this system will allow us to spatiotemporally map cell-cell and cell-ECM forces and evaluate their evolution throughout renal fate specification with the final aim to decouple mechano-related processes sustaining nephron formation from classical biochemical signalling. \n  \nThis PhD Discussion session will be held at Tower I\, 11th floor Baobab room\, at 10:00am. \n  \nWith the support of Joan Oró grant to hire research staff in training (FI 2025)\, 2023 FI-2 00386\, funded by Generalitat de Catalunya and by the European Social Fund Plus. \n \n 
URL:https://ibecbarcelona.eu/event/phd-discussions-ainoa-tejedera-and-zarina-nauryzgaliyeva/
LOCATION:Sala Dolors Aleu\, Cluster II\, IBEC\, Baldiri i Reixac\, Barcelona
CATEGORIES:PhD Discussions Session
ORGANIZER;CN="IBEC":MAILTO:www.ibecbarcelona.eu
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20231020T100000
DTEND;TZID=Europe/Madrid:20231020T113000
DTSTAMP:20260502T121524
CREATED:20231005T130733Z
LAST-MODIFIED:20231010T145141Z
UID:111469-1697796000-1697801400@ibecbarcelona.eu
SUMMARY:PhD Discussions: Thomas Wilson and Judith Fuentes
DESCRIPTION:Multiscale buckling of epithelial shells\nThomas Wilson\, Integrative Cell and Tissue Dynamics group \nNumerous natural and engineered structures are shaped as thin curved shells. When subjected to excessive compressive loading\, these shells undergo buckling instabilities that result in wrinkling patterns with complex dynamics. Epithelial tissues such as those enclosing embryos or lining glandular organs are a class of thin shells that displays three distinctive mechanical features: they are viscoelastic over the time scales of physiological loading\, they carry an active surface tension\, and their stress-bearing elements are distributed across scales. The conditions under which these material properties enable buckling\, and the subsequent structural changes are not understood. Here we establish the buckling dynamics of epithelial shells of controlled geometry over several orders of magnitude in time and space. We developed an experimental system that allows us to sculpt epithelial shells and subject them to controlled pressure differentials. We show that\, under rapid pressure reductions relative to a characteristic viscoelastic time of the system\, the tissue develops buckling patterns with different degrees of symmetry that depend on its size and shape. By contrast\, slow deflations allow the tissues to accommodate large strain variations without buckling. Strikingly\, we find that epithelial buckling is a multiscale phenomenon involving supracellular folds but also subcellular wrinkles in the actin cortex. Additionally\, we can harness the active viscoelastic behaviour of the cell cortex to pattern epithelial folds by rationally directed buckling. Our study shows that epithelial tissues can be understood as hierarchical materials with mechanical instabilities that can be harnessed to engineer morphogenetic events. \n\nEvaluation of self-healing properties in skeletal muscle-based bioactuators\nJudith Fuentes\, Smart Nano-Bio-Devices group \nThree dimensional bioprinting has opened new possibilities for the bioengineering of skeletal muscle models with organization and functionality similar to native tissues. This is key to understand the physiological conditions of skeletal muscle to integrate some of their unique properties\, such as self-healing\, adaptability\, and response to external stimuli\, in biohybrid systems. However\, the inherent self-healing capability of skeletal muscle has not been fully exploited in these advanced biohybrid platforms. In vivo\, skeletal muscle tissue may be repaired via the regenerative function of satellite cells (SC). However\, in in vitro conditions\, these cells are difficult to expand without altering their self-healing potential. Myogenic reserve cells (RC) offer an alternative potentially useful source to implement advanced regenerative capabilities in biohybrid systems. RC present similar properties to SC and arise during in vitro myoblast differentiation when a subpopulation escape from terminal differentiation. This work presents a 3D-bioprinted skeletal muscle bioactuator which self-healing properties have been evaluated after generating physical damage to the tissue\, either by creating cuts or crush injuries. Further studying over the underlying biological events related to muscle repair will be key to moving forward with the design of muscle-based bioactuators with on-demand assisted self-healing properties.
URL:https://ibecbarcelona.eu/event/phd-discussions-thomas-wilson-and-judith-fuentes/
LOCATION:Sala Dolors Aleu\, Cluster II\, IBEC\, Baldiri i Reixac\, Barcelona
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20231215T100000
DTEND;TZID=Europe/Madrid:20231215T110000
DTSTAMP:20260502T121524
CREATED:20231127T122753Z
LAST-MODIFIED:20231204T154540Z
UID:112845-1702634400-1702638000@ibecbarcelona.eu
SUMMARY:PhD Discussions: Zhendong Xie and Júlia Alcàcer
DESCRIPTION:Integrating phenotypic targeting in physiologically-based pharmacokinetics modeling.\nZhendong Xie\, Molecular Bionics group \nSelective drugging\, also known as the “magic bullet\,” is the concept that drugs can target specific molecules\, cells\, or targets while minimising interactions with other parts of the body. Nanoparticles (NPs) with functioned ligands target cells with a certain range of receptors due to the multivalent effect. To develop precision drugs\, it is crucial to understand how NPs are distributed in different organs and interact with different cell types in vivo. Our focus is on investigating the distribution of poly(2-(methacryloyloxy)ethylphosphorylcholine)-poly(2-(diisopropyl-amino)ethyl methacrylate) (PMPC-PDPA) polymersome. We use the PMPC polymersome’s interactions with different receptors to target specific cell groups based on phenotypic association theory (PAT)\, a statistical model based on the description between nanocarriers and cell phenotype (receptor density and glycocalyx). \nWe integrate phenotypic targeting in physiologically-based pharmacokinetics modeling (PBPK) to mimic the distribution of NPs in organs in silico to identify the most selective combination of parameters for precision drugs. The PBPK is built based on the circulation system\, anatomy data\, and cell protein atlas to predict the distribution of NPs among different organs\, considering the advection among various biological fluids\, diffusion of NPs in different organs\, and NPs’ interaction with different cells. A non-Langmiur differential rate equation (NLDRE) is applied to extrapolate the PMPC-cell interaction kinetics based on single-cell level uptake experiments. The association constant/affinity kA/j is derived from the PAT to reveal the selectivity of NPs to different cells. We propose that the difference in kA/j results in a larger distribution and cell targeting discrimination. \nThrough experiments in vivo\, we obtained information about drug distribution among different organs\, the selectivity of NPs to different cells\, and some undetectable parameters such as glycocalyx density. Based on these parameters\, we change the injected dose\, the NP radius\, and the polymerization of the PMPC ligand to simulate the distribution of PMPC in silico and develop a better administration strategy. \n\nExploring host-pathogen interactions: Unraveling the dynamics of Pseudomonas aeruginosa and Burkholderia cenocepacia infection in Galleria mellonella\nJúlia Alcàcer\, Bacterial infections: antimicrobial therapies group \nPseudomonas aeruginosa and Burkholderia cenocepacia are two multidrug-resistant opportunistic pathogens often isolated from the lungs of cystic fibrosis patients. It is known that the presence of more than one species in an infection promotes the appearance of a network of interactions that can lead to an increase in their antimicrobial tolerance or to the evasion of the host immune system. Galleria mellonella has been used as an animal model throughout this study\, as its immune system is comparable to that of mammals\, and it presents practical advantages such as their easy maintenance. With the aim of understanding bacterial and host behaviors after infection\, the survival rate of Galleria mellonella after a P. aeruginosa and B. cenocepacia single and dual-species infection was monitored\, as well as the efficacy of antibiotic treatment to such infections. In order to characterize the infection evolution\, the tissue-specific infection dissemination and hemocyte phagocytosis were evaluated through confocal microscopy.
URL:https://ibecbarcelona.eu/event/phd-discussions-zhendong-xie-and-julia-alcacer/
LOCATION:Sala Dolors Aleu\, Cluster II\, IBEC\, Baldiri i Reixac\, Barcelona
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20240126T100000
DTEND;TZID=Europe/Madrid:20240126T110000
DTSTAMP:20260502T121524
CREATED:20231128T135726Z
LAST-MODIFIED:20240119T112549Z
UID:112917-1706263200-1706266800@ibecbarcelona.eu
SUMMARY:PhD Discussions: Ainhoa Ferret and Marta Badia
DESCRIPTION:3D bioengineered liver for the study of acute and chronic hepatic damage\nAinhoa Ferret\, Biosensors for bioengineering group \nThe liver\, a vital organ\, faces acute and chronic insults that disrupt its normal function. Understanding the mechanisms underlying acute and chronic liver damage is crucial for developing effective treatments. Traditional liver models face several limitations. As a result\, 3D models have emerged as a more physiologically cellular microenvironment for investigating disease progression\, identifying potential therapeutic targets\, and developing new drugs. We developed a 3D liver using human hepatocytes\, HSCs\, and monocytes. The cells were encapsulated in a mixture of GelMA and CMCMA\, and LAP as a photo-initiator. The 3D livers were kept in culture for up to 30 days in serum-free medium. They were challenged with acetaminophen and LPS (APAP-LPS)\, known hepatotoxic compounds\, to recreate the pathophysiological phenotype of liver damage in vitro. Extensive liver damage characterized by hepatic stellate cell (HSC) activation and proliferation was observed upon challenge with APAP-LPS. In vivo\, these cells exhibited the myofibroblast phenotype typical of activated HSCs. Additionally\, impaired gene expression of hepatocyte functionality markers was observed. The transition from monocytes to proinflammatory cytokine-releasing macrophages measured the inflammation level. Notably\, dexamethasone demonstrated potent beneficial effects\, reducing hepatocyte damage\, inhibiting HSC activation\, and decreasing collagen production. These results were observed in both acute (high APAP-LPS concentration/3 days) and chronic (low APAP-LPS concentration/30 days) models. The 3D model presented here demonstrates its value as a versatile platform for drug screening in both acute and chronic liver damage scenarios. Its ability to reproduce critical features of liver pathophysiology\, including hepatocyte functionality impairment\, HSC activation\, and inflammation\, makes it a valuable tool for studying liver diseases and evaluating potential therapeutic interventions. Furthermore\, the adaptability of this model for high-throughput screening provides an opportunity to accelerate the drug discovery process and improve patient outcomes in liver damage-related conditions. \n  \nDisclosures \nConflict of interest: This study is supported by Grifols. \n  \n\nWhat makes a prion behave like a prion? Lessons from deep mutagenesis\nMarta Badia\, Protein phase transitions in health and disease group \nPrions are proteins capable of promoting conformational changes of other protein isoforms. When prion proteins switch from a soluble (non-prion) state to a misfolded (prion) state\, they can bind to each other forming small nuclei that can rapidly incorporate other monomers and form amyloid-like aggregates. Subtle differences in the sequence of prionic proteins are enough to impair the recruitment of monomers into these small nuclei\, creating a barrier for the nucleation of aggregates. Learning how this barrier is established (and overcome) is fundamental to explain prion nucleation and to understand cross-species prion infection. \nYeast prions serve as a good and tractable model to study amyloid formation and protein aggregation. Sup35 is one of the most intensively studied yeast prions and its N-terminal domain is sufficient for prion nucleation and the maintenance of its prionic state. However\, the mechanisms by which Sup35 starts nucleating amyloid aggregates and the features that prevent this nucleation still need to be elucidated. \nUsing deep mutagenesis\, we built a library encompassing all single amino acid changes in the QN-rich region (aa 2-40) of the Sup35 N-terminal domain. We then employed a massively parallel approach that combines high-throughput sequencing with a selection assay that is able to measure Sup35 nucleation in yeast cells. \nBy systematically quantifying the effect of hundreds of mutants in the QN-rich domain of Sup35 we determined the compatibility of each mutation with an effective Sup35 nucleation. Thanks to this dataset\, we identified a nine-residue segment (residues 17-25) crucial for this process. On the other hand\, our comprehensive dataset also uncovers mutants that increase Sup35 nucleation\, gaining mechanistic insights on the nucleation of this model system and how prion species barriers can be overcome.
URL:https://ibecbarcelona.eu/event/phd-discussions-ainoa-ferret-and-marta-badia/
LOCATION:Sala Dolors Aleu\, Cluster II\, IBEC\, Baldiri i Reixac\, Barcelona
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20240301T100000
DTEND;TZID=Europe/Madrid:20240301T110000
DTSTAMP:20260502T121524
CREATED:20240219T144047Z
LAST-MODIFIED:20240222T105448Z
UID:115601-1709287200-1709290800@ibecbarcelona.eu
SUMMARY:PhD Discussions: Alba Herrero y Clement Hallopeau
DESCRIPTION:Molecular imaging to unveil the pathophysiology of metabolic associated fatty liver disease\nAlba Herrero\, Molecular Imaging for Precision Medicine group \nMetabolic-associated fatty liver disease (MAFLD)\, a progressive liver condition rapidly rising to lead to chronic liver disease worldwide\, manifests as metabolic dysregulation\, leading to steatosis\, fibrosis\, and cirrhosis if left untreated. Beyond the liver\, it induces high BMI\, insulin resistance\, and elevated plasma glucose amongst others. Age\, genetics\, and sex influence its clinical presentation\, hindering biomarker detection. Currently\, real-time metabolic monitoring is not readily available in clinical settings. Hyperpolarized Magnetic Resonance Spectroscopic Imaging (HP-MRSI) boosts MR signals\, allowing for real-time metabolic tracking of 13C-labelled substrates\, such as pyruvate\, posing as a solution to this problem.\nWe delineated 6 study groups to evaluate the effects on liver metabolism of specific MAFLD risk factors\, these being diet\, sex\, and genetics. Subjects were monitored throughout the experiment for signs of insulin resistance\, increased plasma glucose\, and BMI levels as MAFLD indicators. Analyzed with a 3T preclinical MRI scanner\, and after injection of hyperpolarized [1-13C]-pyruvate\, the metabolism of pyruvate was tracked in situ\, probing downstream metabolic products such as lactate and alanine.\nMetabolic imaging has the potential to be used in clinical settings to diagnose and track metabolic dysfunctions. Real-time monitoring of pyruvate metabolism using HP-MRSI has revealed alterations across various metabolic conditions\, displaying its clinical potential. \n\nMechanisms of mechanical compartmentalisation in intestinal organoids\nClement Hallopeau\, Integrative Cell and Tissue Dynamics group \nMonolayers of intestinal organoids recapitulate the functional compartmentalisation seen in-vivo.\nCrypt-like regions host stem cells\, Paneth cells and transit amplifying cells\, whereas villus-like regions contain differentiated cells. Measurements of traction forces in these organoids have\nestablished that stem cells push the underlying substrate while the transit-amplifying cells pull it\, defining clear mechanical and functional compartments (Pérez-González\, Ceada et al\, Nat Cell Bio\, 2021). Crypt-villus compartmentalisation is attributed to opposed gradients in Eph/ephrin signaling\, but how these gradients are linked to the mechanical pattern is unknown. To address this question\, we studied the mechanical and functional compartmentalisation in organoids derived from mice lacking EphB2 and EphB3 (EphB2-/-\, EphB3-/-). We found that\, unlike in wild type organoids (WT)\, crypts of EphB2-/-EphB3-/- organoids (KO) expand at the expense of the villuslike region. This phenotype is associated to an increased proliferation of the KO crypts and a decreased expression of the stemness marker olfm4. In mechanical terms\, the 3D traction pattern of the KO crypts is qualitatively similar to the WT\, but forces have a decreased amplitude\, suggesting a decreased tension around the KO crypts. Taken together\, these data establish a link between the mechanical features and the size homeostasis of the functional compartments of the intestinal organoid\, governed by Eph/ephrin signaling.
URL:https://ibecbarcelona.eu/event/phd-discussions-alba-herrero-y-clement-hallopeau/
LOCATION:Sala Dolors Aleu\, Cluster II\, IBEC\, Baldiri i Reixac\, Barcelona
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20240405T100000
DTEND;TZID=Europe/Madrid:20240405T110000
DTSTAMP:20260502T121524
CREATED:20240307T114216Z
LAST-MODIFIED:20240326T130314Z
UID:115873-1712311200-1712314800@ibecbarcelona.eu
SUMMARY:PhD discussions: Gülsun Bagci and Joana Admella
DESCRIPTION:Cell-Derived Extracellular Matrices for 3D in vitro Tumor Models\nGülsun Bagci\, Biomaterials for Regenerative Therapies Group \nDecellularized Extracellular matrices are new scaffolds for bioengineering of 3D tumor-ECM in vitro models. The tunable composition\, properties\, and structure of Cell-derived Matrices (CDMs) make them versatile and easy to use by using desired cell types. Moreover\, deposition of ECM can be achieved by adding specific stimulants such as Macromolecular crowding (MMC) like Ficoll/dextran sulfate or treating with hypoxia/starvation. Our aim is to fabricate CDM by two strategies as 2D culture CDMs from human dermal fibroblasts (hDFs)  or 3D culture CDM from bone marrow human mesenchymal stem cells (BM-hMSCs)/Human Adipose-derived stem cells (hAMSCs) in the presence of MMC/Ascorbic acid/ TGFβ-1  on Poly Lactic acid (PLA) derived microparticles (MPs) to generate 3D and 2D culture CDMs\, which can be used as scaffold for reseeding cancer cells or used as bioinks to generate tumor models for cancer research and for testing anti-cancer drugs. \nIn this study\, we generated 2D culture CDM from hDFs and 3D culture CDMs of BM-hMSCs and hAMSCs. To prepare 2D CDMs\, hDF were treated with Ascorbic acid (AA) or Ficoll\, AA\, TGFβ-1 combination for 2-weeks to increase the deposition of CDM. To fabricate 3D culture CDM\, cells were cultured into PLA MPs. MPs were produced by jet break-up method\, and their size distribution was calculated by ImageJ whereas their porosity was imaged under SEM. Moreover\, MPs were functionalized with fibronectin to enhance the cell adhesion. hMSCs/hAMSCs were seeded on MPs in a spinner flask for 8 hours. Then\, cell-seeded MPs were cultured for 2 weeks to produce CDM. The cellular viability and cell seeding in the MPs were evaluated. The ECM production before and after decellularization was evaluated by BCA\, hydroxyproline\, SEM\, qRT-PCR\, and immunofluorescence. Values were normalized by the total DNA. Microtissues and cells on 2D culture were also decellularized with 50mM NH4OH\, 0.05% TritonX-100 solution and characterized. \nBased on our results\, for hDF cells; Ficoll\, TGFβ-1 and Ascorbic acid combination\, and also ascorbic acid alone treatments increased total protein and total collagen production. For BM-hMSCs\, total collagen and protein after 2-weeks incubation was increased significantly in the presence of Ascorbic acid condition on the fibronectin coated MPs. AA increased total protein and total collagen production for hAMSCs at 3D culture. \nCDMs are promising and tunable biomaterials to establish 3D in vitro tumor models for cancer research. This platform possess a powerful potential for testing anti-cancer drugs  for personalized medicine in the coming years. \n\nExploring the potential of Galleria mellonella for the study of bacterial infections\nJoana Admella\, Bacterial Infections: Antimicrobial Therapies Group \nBacterial infections are becoming more threatening every day. Pathogens such as Pseudomonas aeruginosa\, Staphylococcus aureus\, Mycobacterium abscessus\, or Burkholderia cenocepacia pose significant challenges due to antimicrobial resistance. Our group has extensive experience in studying pathogenic microorganisms\, with a focus on understanding bacterial virulence and biofilm formation. \nThe insect Galleria mellonella is an alternative animal model widely used for studying bacterial infections and evaluating the toxicity of various molecules and materials. It presents a wide range of advantages\, including low cost\, easy maintenance\, and lack of ethical constraints. Furthermore\, very precise doses can be injected\, facilitating the testing of diverse treatments like antibiotics\, nanomedicines\, or even bacteriophages. Notably\, their innate immune system closely resembles that of mammals\, encompassing both cellular and humoral defenses. These features make Galleria mellonella a very valuable model for investigating host-pathogen interactions\, infection dissemination\, and immune response. Here\, we present an overview of this animal model\, showing a variety of methodologies and applications that have enhanced our understanding of bacterial infections and expanded our knowledge of this insect.
URL:https://ibecbarcelona.eu/event/phd-discussions-gulsun-bagci-and-joana-admella/
LOCATION:Sala Dolors Aleu\, Cluster II\, IBEC\, Baldiri i Reixac\, Barcelona
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20241213T100000
DTEND;TZID=Europe/Madrid:20241213T110000
DTSTAMP:20260502T121524
CREATED:20241122T100707Z
LAST-MODIFIED:20241210T142747Z
UID:121781-1734084000-1734087600@ibecbarcelona.eu
SUMMARY:PhD Discussion: Anna Panteleeva and Miguel Gonzalez Martin
DESCRIPTION:Advancing Neurodegenerative Disease Research with Enhanced Brain-on-a-Chip Technology and Integrated Biosensor Systems \nAnna Panteleeva – Nanobioengineering\nNeurodegenerative disorders (NDDs)\, such as Alzheimer’s disease\, remain a critical global health challenge. A key obstacle in drug development is the blood-brain barrier (BBB)\, which plays a crucial role in regulating the exchange of substances between the bloodstream and the brain. While the BBB protects the brain\, its dysfunction contributes to NDD progression\, and it hinders drug delivery\, leaving most therapeutic candidates unsuccessful in clinical trials.\nTraditional animal models have provided valuable insights into NDDs\, but they fall short in fully replicating the complexity of human neural responses. Brain-on-a-chip (BoC) technology has emerged as a promising tool\, offering controlled environments to study neuronal networks. Integrating a BBB component into BoC systems significantly enhances their physiological relevance\, enabling the study of complex BBB properties.\nOur research advances BoC technology by combining a microfluidic device\, multi-electrode array (MEA) technology and biosensors to create a comprehensive BBB model. By co-culturing endothelial cells\, pericytes\, astrocytes\, and neurons\, we replicate key BBB elements and neural interactions. This setup allows real-time monitoring of BBB permeability and neural activity via MEA electrodes\, and neuronal degradation using biosensors. Preliminary results demonstrate promising outcomes\, though further optimization is required.\nThis innovative approach improves the physiological relevance of BoC systems and accelerates drug development and personalized therapies for NDDs\, providing a pathway toward more effective treatments. \nDesigning synthetic mechanosensitive molecules for the mechanical control of cellular transcription \nMiguel Gonzalez Martin – Cellular and Molecular Mechanobiology\nCells sense mechanical signals in the process of mechanotransduction\, activating pathways that govern cell behavior. However\, it remains a challenge to engineer mechanotransduction pathways in a controllable and predictable manner. Here we aim to engineer a synthetic mechanosensitive transcription factor (msTTA). To this end\, we exploit the force induced changes in nuclear transport\, linking nuclear mechanical perturbations to gene expression. To do so\, we are mechanically tuning the passive and facilitated transport properties of the synthetic msTTA. Through this we aim to recapitulate the localization behavior of endogenous mechanosensitive proteins such as YAP or Twist\, but with a synthetic factor that activates genes of choice in a controlled way. Optimizing our reporter cells\, we have set up a novel screening platform with substrates of different rigidity\, from which we expect to identify highly mechanosensitive TF candidates that function in a tunable manner\, as well as to elucidate which features make a transcription factor mechanosensitive. Overall\, we expect to unlock precise transcriptional control through mechanical forces\, and a state-of-the-art directed evolution platform for msTTAs. With the simplicity of this engineered regulatory module\, we expect to describe the minimal elements of mechano-regulation of gene expression\, as well as enabling the use of mechanotransduction in gene circuits control. This will open the field to use mechanotransduction approaches for complex synthetic biology applications.
URL:https://ibecbarcelona.eu/event/phd-discussion-3/
LOCATION:Sala Dolors Aleu\, Cluster II\, IBEC\, Baldiri i Reixac\, Barcelona
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20250124T100000
DTEND;TZID=Europe/Madrid:20250124T110000
DTSTAMP:20260502T121524
CREATED:20241122T101514Z
LAST-MODIFIED:20250107T141720Z
UID:121790-1737712800-1737716400@ibecbarcelona.eu
SUMMARY:PhD Discussion: Kristin Fichna and Gian Marco Tuveri
DESCRIPTION:Kristin Fichna – Smart nano-bio-devices \nGian Marco Tuveri –  Molecular bionics \n 
URL:https://ibecbarcelona.eu/event/phd-discussion-kristin-fichna-and-gian-marco/
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20250411T100000
DTEND;TZID=Europe/Madrid:20250411T110000
DTSTAMP:20260502T121524
CREATED:20250404T103254Z
LAST-MODIFIED:20250404T103254Z
UID:125030-1744365600-1744369200@ibecbarcelona.eu
SUMMARY:PHD Discussion: Miquel Bosch
DESCRIPTION:Force transmission in embryonic-like epithelia\nMiquel Bosch (Integrative Cell and Tissue Dynamics Group) \nDeveloping an adult organism from an embryo is a complex task. Cells need to divide\, differentiate and arrange themselves in complex three-dimensional structures\, a process known as morphogenesis. Apical constriction is a conserved morphogenetic mechanism in the animal kingdom\, but the role of cellular forces during it remains understudied\, especially in the human case. For this reason\, we use human PSCs expressing a novel optogenetic tool\, OptoShroom3. This tool allows to induce apical constriction in vitro on demand\, with precise spatiotemporal control. We study force transmission within the cell layer and to the substrate and find that\, contrary to our intuition\, the apical and basal layer are effectively mechanically decoupled. This decoupling enables long range force transmission in this epiblast-like epithelia. Secondly\, we can study the rheology of the tissue on multiple time and length scales by analyzing the induced deformation field. Since the state of the art for development and disease modelling relies heavily on stem cell systems\, we foresee our study will have broad implications in the field whenever morphogenesis comes at play.
URL:https://ibecbarcelona.eu/event/phd-discussion-miquel-bosch/
LOCATION:Sala Dolors Aleu\, Cluster II\, IBEC\, Baldiri i Reixac\, Barcelona
CATEGORIES:PhD Discussions Session
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