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DTSTART;TZID=Europe/Madrid:20240301T100000
DTEND;TZID=Europe/Madrid:20240301T110000
DTSTAMP:20260424T221904
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:20260424T221904
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:20260424T221904
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:20260424T221904
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:20260424T221904
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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