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DTSTART;TZID=Europe/Madrid:20180629T100000
DTEND;TZID=Europe/Madrid:20180629T110000
DTSTAMP:20260505T151726
CREATED:20180621T110702Z
LAST-MODIFIED:20180626T084027Z
UID:59653-1530266400-1530270000@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Helena Lozano and Martina Maier
DESCRIPTION:Electrical and morphological characterization of bacterial polar flagella\nHelena Lozano\, Nanoscale bioelectrical characterization\nThe electric polarization of proteins in response to external electric fields plays an important role to understand the electrostatic interaction of proteins with charged biomolecules and ions [1]. Even if dielectric studies on individual proteins have not been reported\, yet\, there have been some studies on protein complexes involving a relatively small number of proteins\, such as for instance\, virus capsids and virus tails [2\,3]. I am going to present the results of a dielectric study performed on a third protein complex system\, the bacterial polar flagellum\, which is composed of protein subunits called flagellin arranged in several intertwined chains [4]. In particular\, we perform a comparative study of the dielectric properties of single flagella belonging to two different bacteria types\, namely\, Shewanella oneidensis MR-1 and Pseudomona aeruginosas PAO1. The dielectric properties (dielectric constant) have been obtained by combining Electrostatic Force Microscopy images [2] and 3D finite element numerical calculations. The values obtained are within the range of values obtained with macroscopic techniques [1].\nReferences:\n[1] Simonson\, T.\, Rep. Prog. Phys. 66 (2003) 737–787.\n[2] Fumagalli\, L.\, Esteban-Ferrer\, et al. Nature Materials 11 (2012) 743\n[3] Cuervo\, A.\, Dans\, P. D.\, et al. PNAS 111 (2014) E3624.\n[4] Lozano\, H.\, Fábregas\, R.\, Blanco-Cabra\, N.\, Millán-Solsona\, R. Torrents\, E.\, Gomila\, G. (in preparation). \nRehabilitation of cognitive deficits and depression after stroke\nMartina Maier\, SPECS\nCognitive deficits and depression are common consequences of stroke [1]\, [2]. Both have detrimental effects on quality of life and the activities of daily living [3]. In addition\, they have been linked to poor functional outcome and more severe impairment [4]\, [5]\, [6] than observed in patients without cognitive deficit or depression. Post-stroke depression has been related to cognitive impairment [7]\, but the dynamics of that relationship are not well understood\, as cognitive deficits and depression are typically studied and treated in isolation. The aim of our work is twofold. On one hand\, we investigate in how depression modulates cognitive functioning after a stroke. On the other\, we propose a new rehabilitation method that treats cognitive deficits and depression in conjunction. For this reason\, we conducted a longitudinal randomized clinical trial with chronic stroke patients. All patients had a cognitive impairment as measured with the Montreal Cognitive Assessment. In addition\, they expressed various degrees of depression expressed by varying scores on the Hamilton Depression Scale. Our results so far suggest that the presence of depression modulates attentional processing similarly to a cognitive load in a psychophysical task. Moreover\, we see that depressive patients profited most of the conjunctive cognitive training and that the improvement was most evident in the attention domain. Further analysis will shed light on the underlying mechanisms of this improvement. We hope that this work will aid in not only find better rehabilitation methods\, but also improve current diagnostic tools. \nReferences:\n[1] M. Lesniak\, T. Bak\, W. Czepiel\, J. Seniów\, and A. Czlonkowska\, “Frequency and prognostic value of cognitive disorders in stroke patients\,” Dement. Geriatr. Cogn. Disord.\, vol. 26\, no. 4\, pp. 356–363\, 2008.\n[2] M. L. Hackett and K. Pickles\, “Part I: Frequency of depression after stroke: An updated systematic review and meta-analysis of observational studies\,” Int. J. Stroke\, vol. 9\, pp. 1017–1025\, 2014.\n[3] L. Mercier\, T. Audet\, R. Hébert\, A. Rochette\, and M. F. Dubois\, “Impact of motor\, cognitive\, and perceptual disorders on ability to perform activities of daily living after stroke.\,” Stroke.\, vol. 32\, no. 11\, pp. 2602–2608\, 2001.\n[4] R. G. Robinson and R. E. Jorge\, “Post-stroke depression: A review\,”Am. J. Psychiatry\, vol. 173\, pp. 221–23\, 2016.\n[5] R. Gillen\, H. Tennen\, T. E. McKee\, P. Gernert-Dott\, and G. Affleck\, “Depressive symptoms and history of depression predict rehabilitation efficiency in stroke patients\,” Arch. Phys. Med. Rehabil.\, vol. 82\, pp. 1645–1649\, 2001.\n[6] S. Paolucci\, G. Antonucci\, E. Gialloreti\, M. Traballesi\, S. Lubich\, L. Pratesi\, and L. Palombi\, “Predicting Stroke Inpatient Rehabilitation Outcome: The Prominent Role of Neuropsychological Disorders\,” Eur. Neurol.\, vol. 36\, no. 6\, pp. 385–390\, 1996.\n[7] M. L. Kauhanen\, J. T. Korpelainen\, P. Hiltunen\, E. Brusin\, H. Mononen\, R. Maatta\, et al.\, “Poststroke depression correlates with cognitive impairment and neurological deficits\,” Stroke\, vol. 30\, pp. 1875–1880\, 1999.
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-helena-lozano-and-martina-maier/
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:20180629T100000
DTEND;TZID=Europe/Madrid:20180629T110000
DTSTAMP:20260505T151726
CREATED:20180621T110702Z
LAST-MODIFIED:20180621T110702Z
UID:96268-1530266400-1530270000@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Helena Lozano and Martina Maier
DESCRIPTION:Electrical and morphological characterization of bacterial polar flagella\nHelena Lozano\, Nanoscale bioelectrical characterization\nThe electric polarization of proteins in response to external electric fields plays an important role to understand the electrostatic interaction of proteins with charged biomolecules and ions [1]. Even if dielectric studies on individual proteins have not been reported\, yet\, there have been some studies on protein complexes involving a relatively small number of proteins\, such as for instance\, virus capsids and virus tails [2\,3]. I am going to present the results of a dielectric study performed on a third protein complex system\, the bacterial polar flagellum\, which is composed of protein subunits called flagellin arranged in several intertwined chains [4]. In particular\, we perform a comparative study of the dielectric properties of single flagella belonging to two different bacteria types\, namely\, Shewanella oneidensis MR-1 and Pseudomona aeruginosas PAO1. The dielectric properties (dielectric constant) have been obtained by combining Electrostatic Force Microscopy images [2] and 3D finite element numerical calculations. The values obtained are within the range of values obtained with macroscopic techniques [1].\nReferences:\n[1] Simonson\, T.\, Rep. Prog. Phys. 66 (2003) 737–787.\n[2] Fumagalli\, L.\, Esteban-Ferrer\, et al. Nature Materials 11 (2012) 743\n[3] Cuervo\, A.\, Dans\, P. D.\, et al. PNAS 111 (2014) E3624.\n[4] Lozano\, H.\, Fábregas\, R.\, Blanco-Cabra\, N.\, Millán-Solsona\, R. Torrents\, E.\, Gomila\, G. (in preparation). \nRehabilitation of cognitive deficits and depression after stroke\nMartina Maier\, SPECS\nCognitive deficits and depression are common consequences of stroke [1]\, [2]. Both have detrimental effects on quality of life and the activities of daily living [3]. In addition\, they have been linked to poor functional outcome and more severe impairment [4]\, [5]\, [6] than observed in patients without cognitive deficit or depression. Post-stroke depression has been related to cognitive impairment [7]\, but the dynamics of that relationship are not well understood\, as cognitive deficits and depression are typically studied and treated in isolation. The aim of our work is twofold. On one hand\, we investigate in how depression modulates cognitive functioning after a stroke. On the other\, we propose a new rehabilitation method that treats cognitive deficits and depression in conjunction. For this reason\, we conducted a longitudinal randomized clinical trial with chronic stroke patients. All patients had a cognitive impairment as measured with the Montreal Cognitive Assessment. In addition\, they expressed various degrees of depression expressed by varying scores on the Hamilton Depression Scale. Our results so far suggest that the presence of depression modulates attentional processing similarly to a cognitive load in a psychophysical task. Moreover\, we see that depressive patients profited most of the conjunctive cognitive training and that the improvement was most evident in the attention domain. Further analysis will shed light on the underlying mechanisms of this improvement. We hope that this work will aid in not only find better rehabilitation methods\, but also improve current diagnostic tools. \nReferences:\n[1] M. Lesniak\, T. Bak\, W. Czepiel\, J. Seniów\, and A. Czlonkowska\, “Frequency and prognostic value of cognitive disorders in stroke patients\,” Dement. Geriatr. Cogn. Disord.\, vol. 26\, no. 4\, pp. 356–363\, 2008.\n[2] M. L. Hackett and K. Pickles\, “Part I: Frequency of depression after stroke: An updated systematic review and meta-analysis of observational studies\,” Int. J. Stroke\, vol. 9\, pp. 1017–1025\, 2014.\n[3] L. Mercier\, T. Audet\, R. Hébert\, A. Rochette\, and M. F. Dubois\, “Impact of motor\, cognitive\, and perceptual disorders on ability to perform activities of daily living after stroke.\,” Stroke.\, vol. 32\, no. 11\, pp. 2602–2608\, 2001.\n[4] R. G. Robinson and R. E. Jorge\, “Post-stroke depression: A review\,”Am. J. Psychiatry\, vol. 173\, pp. 221–23\, 2016.\n[5] R. Gillen\, H. Tennen\, T. E. McKee\, P. Gernert-Dott\, and G. Affleck\, “Depressive symptoms and history of depression predict rehabilitation efficiency in stroke patients\,” Arch. Phys. Med. Rehabil.\, vol. 82\, pp. 1645–1649\, 2001.\n[6] S. Paolucci\, G. Antonucci\, E. Gialloreti\, M. Traballesi\, S. Lubich\, L. Pratesi\, and L. Palombi\, “Predicting Stroke Inpatient Rehabilitation Outcome: The Prominent Role of Neuropsychological Disorders\,” Eur. Neurol.\, vol. 36\, no. 6\, pp. 385–390\, 1996.\n[7] M. L. Kauhanen\, J. T. Korpelainen\, P. Hiltunen\, E. Brusin\, H. Mononen\, R. Maatta\, et al.\, “Poststroke depression correlates with cognitive impairment and neurological deficits\,” Stroke\, vol. 30\, pp. 1875–1880\, 1999.
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-helena-lozano-and-martina-maier-2/
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:20181026T100000
DTEND;TZID=Europe/Madrid:20181026T110000
DTSTAMP:20260505T151726
CREATED:20181019T082001Z
LAST-MODIFIED:20181019T082001Z
UID:96323-1540548000-1540551600@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Anna Vila and Alexandre Gomila
DESCRIPTION:Engineering of 3D Small Intestinal Mucosa Models\nAnna Vila\, Biomimetic Systems for Cell Engineering\nHydrogels have been used as a scaffold for engineering tissue-like structures due to their biocompatibility and properties similar to the extracellular matrix. There are two main types of hydrogels (i) natural hydrogels\, such as gelatin\, which are biodegradable and present cell adhesion motifs and (ii) synthetic hydrogels\, such as poly(ethylene glycol) diacrylate (PEGDA)\, which are non-biodegradable and can withstand long-term cell cultures but do not have bioadhesion sequences [El-Sherbiny M.I. et al.\, 2013]. Both types of hydrogels present complementary benefits. \nFor this reason\, we fabricated a hydrogel co-polymer composed of gelatin methacrylate (GelMA) co-polymerized with PEGDA [Hutson. B.C. et al.\, 2011]. We employed a single-step\, moldless\, UV-photolithography-based fabrication technique [Castaño A. et al.\, submitted] to fabricate scaffolds mimicking the 3D architecture of the small intestinal mucosa. Using this approach\, we obtained hydrogel co-polymers with finger-like microstructures\, with the roundness and dimensions found in the villi of the native tissue. Mechanical and physicochemical properties such as an approach of the Young’s modulus\, degradation rate and swelling ratio of the hydrogels have been characterized. Adding PEGDA to the GelMA hydrogels have provided hydrogels with lower degradation and higher Young’s modulus\, which ca be easily tuned by changing the composition of GelMA and PEGDA polymers. Furthermore\, we have demonstrated that our scaffolds support the growth and differentiation of intestinal epithelial Caco-2 cells up to 21 days\, obtaining a matured epithelial monolayer with effective tissue barrier properties. \nAdditionally\, we increased the complexity of our model of the small intestinal mucosa by incorporating an additional cell compartment to mimic the stroma of the in vivo tissue. To do that\, we embedded 3T3-NIH fibroblasts in our scaffolds during the photopolymerization procedure. Then\, we cultured Caco-2 cells on top of the 3T3-NIH fibroblast-laden hydrogels up to 21 days. Our preliminary results showed that the co-culture of Caco-2 cells with 3T3-NIH fibroblasts favours the epithelial cell growth and improves their barrier function. Taking all together\, we have generated an intestinal mucosa model that allows for the co-culture of different intestinal cell types distributed in compartments\, mimicking the spatial-physiological features of the small intestinal mucosa. We believe our model better recapitulates cell-cell crosstalk and cell-matrix interactions found in vivo\, being an improved alternative for the cell-base in vitro assays. \n  \nIn vivo photomodulation of GABA and Glycine receptor channels\nAlexandre Gomila\, Nanoprobes and Nanoswitches\nNeuronal networks are highly complex interactions\, which determine even the finest behaviour. The major inhibitory pathways in the central nervous system (CNS) act through chloride ion flux\, which are mostly driven by fast-acting ionotropic GABAA and Glycine receptors (GlyR). All of them share structural similarities and belong to pentameric ligand-gated ion channels of the Cys-loop family. Photoswitchable molecules have become a powerful tool in any applied field of bioscience\, and are broadly used in biomedical research due to their capacity for enlightening biological aspects from their very basics\, such as molecular level\, up to entire neuronal networks.\nPhotopharmacology has proven to be advantageous for spatial and temporal control of biological processes without interfering the system natural dynamics and outcomes. Physiology can be tuned with photomimetic ligands and naturally occurring complex network responses can be segmented into light dependent activities discerning relevant data from a vast matrix of results. As these new tools are broadly used for biomedical purposes and most of them focused towards medical applications\, an interpretative analytical platform is needed to screen and identify potential photoswitchable molecules. \nZebrafish (Danio rerio) larvae constitute an excellent animal model for studying and screening photoswitchable molecules in vivo. Zebrafish present a transparent body during larval stages\, and therefore are capable of receiving specific and determined light applications. From the 19th hour post fertilisation they acquire behavioural traits\, from spontaneous twisting movements to full swimming capacities\, which are easily traceable and measurable. The use of up to 96 animals simultaneously allows a parallel high throughput data recovery system to analyse high complexity movements and behaviours\, all of it with the use of photopharmacology. Here\, we aimed at introducing an effective and reliable methodology for high throughput screening of photoswitchable compounds\, including photopharmacological derivatives or peptidoswitches\, for any in vivo possible target\, from specific neuronal correlated diseases up to possible toxicological outcomes. We focused on the study of the main inhibitory neuronal pathways and their locomotion outcomes on a reliable and comparable animal model. \nHence\, several photoswitchable compounds with a common benzodiazepine core and an azobenzene photoswitchable moiety were tested. A first light dependent activity ratio was applied in order to discern the most promising candidates. We identified the UR-DW290 molecule as a light dependent trigger of activity in larvae zebrafish. Larvae zebrafish treated with UR-DW290 maintained higher activity in terms of swimming distance (mm) during the relaxation period and UV-Blue light cycles in comparison to controls. Whole-cell recordings of GABAA and glycine mediated currents by URDW290 showed a potentiating of inhibition when irradiated with ultraviolet light in comparison to visible light illumination. \nWe propose the combination of high through-put screening and optopharmacology tools for the study and characterisation of zebrafish larvae behaviour focusing on their swimming activity. We identified a first photoswitchable molecule for glycine receptor modulation in vitro and in vivo\, UR-DW290\, which increases basal activity in zebrafish larvae. This increase is tuneable with UV and Blue light illumniation.
URL:https://ibecbarcelona.eu/Anna+Vila+and+Alexandre+Gomila
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:20181026T100000
DTEND;TZID=Europe/Madrid:20181026T110000
DTSTAMP:20260505T151727
CREATED:20181019T082001Z
LAST-MODIFIED:20181019T082223Z
UID:62113-1540548000-1540551600@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Anna Vila and Alexandre Gomila
DESCRIPTION:Engineering of 3D Small Intestinal Mucosa Models\nAnna Vila\, Biomimetic Systems for Cell Engineering\nHydrogels have been used as a scaffold for engineering tissue-like structures due to their biocompatibility and properties similar to the extracellular matrix. There are two main types of hydrogels (i) natural hydrogels\, such as gelatin\, which are biodegradable and present cell adhesion motifs and (ii) synthetic hydrogels\, such as poly(ethylene glycol) diacrylate (PEGDA)\, which are non-biodegradable and can withstand long-term cell cultures but do not have bioadhesion sequences [El-Sherbiny M.I. et al.\, 2013]. Both types of hydrogels present complementary benefits. \nFor this reason\, we fabricated a hydrogel co-polymer composed of gelatin methacrylate (GelMA) co-polymerized with PEGDA [Hutson. B.C. et al.\, 2011]. We employed a single-step\, moldless\, UV-photolithography-based fabrication technique [Castaño A. et al.\, submitted] to fabricate scaffolds mimicking the 3D architecture of the small intestinal mucosa. Using this approach\, we obtained hydrogel co-polymers with finger-like microstructures\, with the roundness and dimensions found in the villi of the native tissue. Mechanical and physicochemical properties such as an approach of the Young’s modulus\, degradation rate and swelling ratio of the hydrogels have been characterized. Adding PEGDA to the GelMA hydrogels have provided hydrogels with lower degradation and higher Young’s modulus\, which ca be easily tuned by changing the composition of GelMA and PEGDA polymers. Furthermore\, we have demonstrated that our scaffolds support the growth and differentiation of intestinal epithelial Caco-2 cells up to 21 days\, obtaining a matured epithelial monolayer with effective tissue barrier properties. \nAdditionally\, we increased the complexity of our model of the small intestinal mucosa by incorporating an additional cell compartment to mimic the stroma of the in vivo tissue. To do that\, we embedded 3T3-NIH fibroblasts in our scaffolds during the photopolymerization procedure. Then\, we cultured Caco-2 cells on top of the 3T3-NIH fibroblast-laden hydrogels up to 21 days. Our preliminary results showed that the co-culture of Caco-2 cells with 3T3-NIH fibroblasts favours the epithelial cell growth and improves their barrier function. Taking all together\, we have generated an intestinal mucosa model that allows for the co-culture of different intestinal cell types distributed in compartments\, mimicking the spatial-physiological features of the small intestinal mucosa. We believe our model better recapitulates cell-cell crosstalk and cell-matrix interactions found in vivo\, being an improved alternative for the cell-base in vitro assays. \n  \nIn vivo photomodulation of GABA and Glycine receptor channels\nAlexandre Gomila\, Nanoprobes and Nanoswitches\nNeuronal networks are highly complex interactions\, which determine even the finest behaviour. The major inhibitory pathways in the central nervous system (CNS) act through chloride ion flux\, which are mostly driven by fast-acting ionotropic GABAA and Glycine receptors (GlyR). All of them share structural similarities and belong to pentameric ligand-gated ion channels of the Cys-loop family. Photoswitchable molecules have become a powerful tool in any applied field of bioscience\, and are broadly used in biomedical research due to their capacity for enlightening biological aspects from their very basics\, such as molecular level\, up to entire neuronal networks.\nPhotopharmacology has proven to be advantageous for spatial and temporal control of biological processes without interfering the system natural dynamics and outcomes. Physiology can be tuned with photomimetic ligands and naturally occurring complex network responses can be segmented into light dependent activities discerning relevant data from a vast matrix of results. As these new tools are broadly used for biomedical purposes and most of them focused towards medical applications\, an interpretative analytical platform is needed to screen and identify potential photoswitchable molecules. \nZebrafish (Danio rerio) larvae constitute an excellent animal model for studying and screening photoswitchable molecules in vivo. Zebrafish present a transparent body during larval stages\, and therefore are capable of receiving specific and determined light applications. From the 19th hour post fertilisation they acquire behavioural traits\, from spontaneous twisting movements to full swimming capacities\, which are easily traceable and measurable. The use of up to 96 animals simultaneously allows a parallel high throughput data recovery system to analyse high complexity movements and behaviours\, all of it with the use of photopharmacology. Here\, we aimed at introducing an effective and reliable methodology for high throughput screening of photoswitchable compounds\, including photopharmacological derivatives or peptidoswitches\, for any in vivo possible target\, from specific neuronal correlated diseases up to possible toxicological outcomes. We focused on the study of the main inhibitory neuronal pathways and their locomotion outcomes on a reliable and comparable animal model. \nHence\, several photoswitchable compounds with a common benzodiazepine core and an azobenzene photoswitchable moiety were tested. A first light dependent activity ratio was applied in order to discern the most promising candidates. We identified the UR-DW290 molecule as a light dependent trigger of activity in larvae zebrafish. Larvae zebrafish treated with UR-DW290 maintained higher activity in terms of swimming distance (mm) during the relaxation period and UV-Blue light cycles in comparison to controls. Whole-cell recordings of GABAA and glycine mediated currents by URDW290 showed a potentiating of inhibition when irradiated with ultraviolet light in comparison to visible light illumination. \nWe propose the combination of high through-put screening and optopharmacology tools for the study and characterisation of zebrafish larvae behaviour focusing on their swimming activity. We identified a first photoswitchable molecule for glycine receptor modulation in vitro and in vivo\, UR-DW290\, which increases basal activity in zebrafish larvae. This increase is tuneable with UV and Blue light illumniation.
URL:https://ibecbarcelona.eu/Anna+Vila+and+Alexandre+Gomila
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:20181130T100000
DTEND;TZID=Europe/Madrid:20181130T110000
DTSTAMP:20260505T151727
CREATED:20181120T084540Z
LAST-MODIFIED:20181120T084540Z
UID:96347-1543572000-1543575600@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Martí Checa and Javier Rodríguez
DESCRIPTION:Nanoscale Dielectric Imaging by 3D-Electrostatic Force Microscopy\nMartí Checa\, Nanoscale bioelectrical characterization\nWe present Electrostatic Force Volume Microscopy (EFVM) for nanoscale dielectric imaging. EFVM is a new 3D-SPM technique\, based in the acquisition of electrostatic force approach curves at each point of a sample and its post-processing and quantification to obtain both Electrostatic Force Microscopy (EFM) images and dielectric constant maps. We show that with a single set of EFVM data one can obtain EFM images in all currently available EFM imaging modes (e.g. constant height\, lift mode\, constant electric force\, etc.) and at any desired tip-sample distance or electric force set point. EFVM enables\, in addition\, obtaining EFM images under acquisition settings that cannot be implemented in any existing EFM instrument. Finally\, EFVM allows obtaining maps of the dielectric constant of the sample with unparalleled accuracy and spatial resolution\, irrespectively of the sample topography. We report applications of EFVM to thin oxide films\, silver nanowires and single bacterial cells to show the broad applicability of the technique. EFVM is expected to have an important impact in the nanoscale dielectric mapping of topographically complex samples in Materials and Life Sciences. \n  \nSudden cardiac death risk stratification of idiopathic cardiomyopathy patients by the application of cardiovascular coupling analysis\nJavier Rodríguez\, Biomedical signal processing and interpretation\nCardiovascular diseases are one of the most common cause of death. Early detection of patients at high risk of sudden cardiac death (SCD) is still an issue. The aim of this study was to analyze the cardio-vascular couplings based on heart rate variability (HRV) and blood pressure variability (BPV) analysis in order to introduce new indices that allow noninvasive risk stratification in idiopathic dilated cardiomyopathy patients (IDC). \nHigh-resolution electrocardiogram (ECG) and continuous noninvasive blood pressure (BP) signals were recorded from 91 IDC patients and 49 healthy subjects (CON) for 30 minutes. During a follow-up period of 2 years\, 14 patients either died or suffered life-threatening complications due to their cardiac condition. From the ECG and BP signals\, the beat-to-beat interval\, and systolic and diastolic blood pressure values were extracted. All this new information was analyzed\, in univariate and bivariate ways\, using the segmented Poincaré plot analysis\, the high resolution joint symbolic dynamics and the normalized short time partial directed coherence methods. Indices with statistical significance between different SCD risk levels were selected. Support vector machine (SVM) models were built in order to classify these patients by their level of SCD risk. Patients at high risk of SCD (IDCHR) presented lowered HRV and increased BPV compared to both the low risk patients (IDCLR) and the control subjects\, suggesting a depression in their vagal activity and a compensation from the sympathetic activity. The coupling strength from both\, the systolic and diastolic blood pressure to the cardiac activity were stronger in high risk patients. Additionally\, the cardio-systolic coupling analysis revealed that the systolic influence over the heart rate gets weaker as the risk increases. The SVM IDCLR vs IDCHR model achieved 98.9% accuracy with an area under the curve (AUC) of 0.96. When comparing IDC vs CON groups\, 93.6% and 0.94 accuracy and AUC were obtained\, respectively. In order to simulate the case were the original status of the subject is unknown\, a cascade model was built fusing the aforementioned models\, achieving 94.4% accuracy. \nIn conclusion\, this study introduced a novel method of SCD risk stratification of IDC patients based on new indices from coupling analysis and non-linear HRV and BPV. We uncovered some of the complex interactions within the autonomic regulation in this type of patients. \n 
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-marti-checa-and-javier-rodriguez-2/
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:20181130T100000
DTEND;TZID=Europe/Madrid:20181130T110000
DTSTAMP:20260505T151727
CREATED:20181120T084540Z
LAST-MODIFIED:20181120T084540Z
UID:63427-1543572000-1543575600@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Martí Checa and Javier Rodríguez
DESCRIPTION:Nanoscale Dielectric Imaging by 3D-Electrostatic Force Microscopy\nMartí Checa\, Nanoscale bioelectrical characterization\nWe present Electrostatic Force Volume Microscopy (EFVM) for nanoscale dielectric imaging. EFVM is a new 3D-SPM technique\, based in the acquisition of electrostatic force approach curves at each point of a sample and its post-processing and quantification to obtain both Electrostatic Force Microscopy (EFM) images and dielectric constant maps. We show that with a single set of EFVM data one can obtain EFM images in all currently available EFM imaging modes (e.g. constant height\, lift mode\, constant electric force\, etc.) and at any desired tip-sample distance or electric force set point. EFVM enables\, in addition\, obtaining EFM images under acquisition settings that cannot be implemented in any existing EFM instrument. Finally\, EFVM allows obtaining maps of the dielectric constant of the sample with unparalleled accuracy and spatial resolution\, irrespectively of the sample topography. We report applications of EFVM to thin oxide films\, silver nanowires and single bacterial cells to show the broad applicability of the technique. EFVM is expected to have an important impact in the nanoscale dielectric mapping of topographically complex samples in Materials and Life Sciences. \n  \nSudden cardiac death risk stratification of idiopathic cardiomyopathy patients by the application of cardiovascular coupling analysis\nJavier Rodríguez\, Biomedical signal processing and interpretation\nCardiovascular diseases are one of the most common cause of death. Early detection of patients at high risk of sudden cardiac death (SCD) is still an issue. The aim of this study was to analyze the cardio-vascular couplings based on heart rate variability (HRV) and blood pressure variability (BPV) analysis in order to introduce new indices that allow noninvasive risk stratification in idiopathic dilated cardiomyopathy patients (IDC). \nHigh-resolution electrocardiogram (ECG) and continuous noninvasive blood pressure (BP) signals were recorded from 91 IDC patients and 49 healthy subjects (CON) for 30 minutes. During a follow-up period of 2 years\, 14 patients either died or suffered life-threatening complications due to their cardiac condition. From the ECG and BP signals\, the beat-to-beat interval\, and systolic and diastolic blood pressure values were extracted. All this new information was analyzed\, in univariate and bivariate ways\, using the segmented Poincaré plot analysis\, the high resolution joint symbolic dynamics and the normalized short time partial directed coherence methods. Indices with statistical significance between different SCD risk levels were selected. Support vector machine (SVM) models were built in order to classify these patients by their level of SCD risk. Patients at high risk of SCD (IDCHR) presented lowered HRV and increased BPV compared to both the low risk patients (IDCLR) and the control subjects\, suggesting a depression in their vagal activity and a compensation from the sympathetic activity. The coupling strength from both\, the systolic and diastolic blood pressure to the cardiac activity were stronger in high risk patients. Additionally\, the cardio-systolic coupling analysis revealed that the systolic influence over the heart rate gets weaker as the risk increases. The SVM IDCLR vs IDCHR model achieved 98.9% accuracy with an area under the curve (AUC) of 0.96. When comparing IDC vs CON groups\, 93.6% and 0.94 accuracy and AUC were obtained\, respectively. In order to simulate the case were the original status of the subject is unknown\, a cascade model was built fusing the aforementioned models\, achieving 94.4% accuracy. \nIn conclusion\, this study introduced a novel method of SCD risk stratification of IDC patients based on new indices from coupling analysis and non-linear HRV and BPV. We uncovered some of the complex interactions within the autonomic regulation in this type of patients. \n 
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-marti-checa-and-javier-rodriguez/
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:20190329T100000
DTEND;TZID=Europe/Madrid:20190329T120000
DTSTAMP:20260505T151727
CREATED:20190325T090048Z
LAST-MODIFIED:20190325T090056Z
UID:66075-1553853600-1553860800@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Elena Lantero and Manuel López
DESCRIPTION:Targeting Plasmodium falciparum with DNA aptamers\nElena Lantero\, Nanomalaria\nMalaria still remains as one of the main causes of mortality in many developing countries. Caused by parasitic infection of Plasmodium species\, the World Health Organization has launched an ambitious plan to eradicate malaria\, which will require population mass screening and treatment. In this context\, the current diagnostic gold standard is light microscopy of peripheral blood smears\, which is time and labor intensive\, and needs prepared personnel and continuous training. Alternatively\, antigen-based rapid tests have limited sensitivity and do not provide quantitative measure; and PCR-based molecular methods\, although sensitive\, demand for highly trained personnel and costly reactives. Besides\, most current antimalarials have known resistances and new forms of treatment such as targeted delivery are interesting tools to prevent further spreading of such resistances. \nAccordingly\, malaria massive screening and treatment will require new rapid\, sensitive\, simple and economically affordable methods\, able to detect even asymptomatic infected patients and low-density infections. Screening for new bioreceptors is required in order to increase the sensitivity of current antigen-based malaria rapid diagnosis or to develop new treatments. Antibody production often involves the use of laboratory animals and is time-consuming and costly\, especially when the target is Plasmodium\, whose variable antigen expression complicates the development of long-lived biomarkers. To circumvent these obstacles we have applied the Systematic Evolution of Ligands by EXponential enrichment (SELEX) method to the rapid identification of DNA aptamers against Plasmodium-infected red blood cells (pRBCs). This type of synthetic bioreceptor is expected to display higher dry-storage and lyophilisation stability than antibodies. Five 70 bp-long ssDNA sequences having a highly specific binding of pRBCs versus non-infected erythrocytes have been identified by using cell-SELEX with fixed pRBCs. \nPhotons to electrons:  Single molecule and time resolved Photosynthetic complex electron transfer study\nManuel López \, Nanoprobes and nanoswitches\nWe present our work on the electron transfer process of plant photosynthetic complex I (PSI). PSI is a membrane protein complex that captures sunlight energy and uses it to shuttle and energize electrons throughout thylakoid membrane\, bringing them from a low energy state in one side of the membrane to a very energetic state in the other side. \nWe study the electron transfer process between photo-oxidized and photo-reduced peripherical cofactors of the protein and their respective protein redox partners performing electrochemical bulk and single molecule photocurrent measurements as protein sample is irradiated with LED and femtosecond pulsed lasers. \n 
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-elena-lantero-and-manuel-lopez/
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:20190329T100000
DTEND;TZID=Europe/Madrid:20190329T120000
DTSTAMP:20260505T151727
CREATED:20190325T090048Z
LAST-MODIFIED:20190325T090048Z
UID:96422-1553853600-1553860800@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Elena Lantero and Manuel López
DESCRIPTION:Targeting Plasmodium falciparum with DNA aptamers\nElena Lantero\, Nanomalaria\nMalaria still remains as one of the main causes of mortality in many developing countries. Caused by parasitic infection of Plasmodium species\, the World Health Organization has launched an ambitious plan to eradicate malaria\, which will require population mass screening and treatment. In this context\, the current diagnostic gold standard is light microscopy of peripheral blood smears\, which is time and labor intensive\, and needs prepared personnel and continuous training. Alternatively\, antigen-based rapid tests have limited sensitivity and do not provide quantitative measure; and PCR-based molecular methods\, although sensitive\, demand for highly trained personnel and costly reactives. Besides\, most current antimalarials have known resistances and new forms of treatment such as targeted delivery are interesting tools to prevent further spreading of such resistances. \nAccordingly\, malaria massive screening and treatment will require new rapid\, sensitive\, simple and economically affordable methods\, able to detect even asymptomatic infected patients and low-density infections. Screening for new bioreceptors is required in order to increase the sensitivity of current antigen-based malaria rapid diagnosis or to develop new treatments. Antibody production often involves the use of laboratory animals and is time-consuming and costly\, especially when the target is Plasmodium\, whose variable antigen expression complicates the development of long-lived biomarkers. To circumvent these obstacles we have applied the Systematic Evolution of Ligands by EXponential enrichment (SELEX) method to the rapid identification of DNA aptamers against Plasmodium-infected red blood cells (pRBCs). This type of synthetic bioreceptor is expected to display higher dry-storage and lyophilisation stability than antibodies. Five 70 bp-long ssDNA sequences having a highly specific binding of pRBCs versus non-infected erythrocytes have been identified by using cell-SELEX with fixed pRBCs. \nPhotons to electrons:  Single molecule and time resolved Photosynthetic complex electron transfer study\nManuel López \, Nanoprobes and nanoswitches\nWe present our work on the electron transfer process of plant photosynthetic complex I (PSI). PSI is a membrane protein complex that captures sunlight energy and uses it to shuttle and energize electrons throughout thylakoid membrane\, bringing them from a low energy state in one side of the membrane to a very energetic state in the other side. \nWe study the electron transfer process between photo-oxidized and photo-reduced peripherical cofactors of the protein and their respective protein redox partners performing electrochemical bulk and single molecule photocurrent measurements as protein sample is irradiated with LED and femtosecond pulsed lasers. \n 
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-elena-lantero-and-manuel-lopez-2/
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:20190426T100000
DTEND;TZID=Europe/Madrid:20190426T120000
DTSTAMP:20260505T151727
CREATED:20190424T090132Z
LAST-MODIFIED:20190424T100103Z
UID:66453-1556272800-1556280000@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Andrés Marco and Davia Prischich
DESCRIPTION:An iCRISPR Platform for Human Functional Genetics in Human Pluripotent Stem Cells (hPSCs)\nAndrés Marco\, Pluripotency for organ regeneration\nSelf-renewal and pluripotency are the two major functional properties defining human pluripotent stem cells (hPSCs)\, allowing them to be cultured indefinitely in a dish and maintaining their capacity to differentiate to virtually any human cell lineage\, tissue or organ. Hence\, they represent an ideal model for studying cellular and multicellular behaviors in both physiological and pathological conditions. \nUp until recently\, the genome of hPSCs was difficult to manipulate\, limiting considerably their use for functional genetics. To solve this problem\, here we present the results of our ongoing effort to engineer an iCRISPR platform for highly efficient genome engineering in hPSCs. We have targeted the safe harbor AAVS1 locus using an inducible Cas9 editing vector (iC2)\, an inducible dCas9 activator (iCa) or an inducible dCas9 repressor (iCr). iCRISPR allows inducible gene knockout\, gene upregulation and gene repression. \n All together\, these lines will greatly expand the repertoire of applications that can be addressed with hPSCs. Our final goal is to use the iCRISPR platform to dissect kidney development and disease in hPSC-derived kidney organoids. \n\nTraffic Lights peptides to photocontrol clathrin-mediated endocytosis in yeasts\nDavia Prischich\, Nanoprobes and nanoswitches\nClathrin-mediated endocytosis (CME) is crucial to all eukaryotic cells. It is implicated in a variety of cellular processes that range from nutrient uptake\, signal transduction and regulation of the membrane components including surface proteins. The functioning of this transient machinery requires a complex network of proteins that cannot be untangled only by means of genetic modification and immunological depletion. In this sense\, photopharmacology provides a powerful aid by complementing the selectivity of drugs with the remote and reversible control offered by light. \nTraffic Lights (TLs) peptides are cell-permeable\, photoswitchable inhibitors specifically developed to target the main adaptor complex of the CME machinery. These peptides\, named TL1 and TL2\, have already proved capable of inhibiting CME in a light-regulated manner when tested in mammalian cells. Here we show that TL peptides retain their activity in yeast. After having confirmed photoregulation of CME events in this extremely versatile eukaryotic model system\, we now aim to achieve in situ activation of the peptide so to directly address the role of endocytosis in cellular processes such as cytokinesis or cell migration.
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-andres-marco-and-davia-prischich/
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:20190426T100000
DTEND;TZID=Europe/Madrid:20190426T120000
DTSTAMP:20260505T151727
CREATED:20190424T090132Z
LAST-MODIFIED:20190424T090132Z
UID:96449-1556272800-1556280000@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Andrés Marco and Davia Prischich
DESCRIPTION:An iCRISPR Platform for Human Functional Genetics in Human Pluripotent Stem Cells (hPSCs)\nAndrés Marco\, Pluripotency for organ regeneration\nSelf-renewal and pluripotency are the two major functional properties defining human pluripotent stem cells (hPSCs)\, allowing them to be cultured indefinitely in a dish and maintaining their capacity to differentiate to virtually any human cell lineage\, tissue or organ. Hence\, they represent an ideal model for studying cellular and multicellular behaviors in both physiological and pathological conditions. \nUp until recently\, the genome of hPSCs was difficult to manipulate\, limiting considerably their use for functional genetics. To solve this problem\, here we present the results of our ongoing effort to engineer an iCRISPR platform for highly efficient genome engineering in hPSCs. We have targeted the safe harbor AAVS1 locus using an inducible Cas9 editing vector (iC2)\, an inducible dCas9 activator (iCa) or an inducible dCas9 repressor (iCr). iCRISPR allows inducible gene knockout\, gene upregulation and gene repression. \n All together\, these lines will greatly expand the repertoire of applications that can be addressed with hPSCs. Our final goal is to use the iCRISPR platform to dissect kidney development and disease in hPSC-derived kidney organoids. \n\nTraffic Lights peptides to photocontrol clathrin-mediated endocytosis in yeasts\nDavia Prischich\, Nanoprobes and nanoswitches\nClathrin-mediated endocytosis (CME) is crucial to all eukaryotic cells. It is implicated in a variety of cellular processes that range from nutrient uptake\, signal transduction and regulation of the membrane components including surface proteins. The functioning of this transient machinery requires a complex network of proteins that cannot be untangled only by means of genetic modification and immunological depletion. In this sense\, photopharmacology provides a powerful aid by complementing the selectivity of drugs with the remote and reversible control offered by light. \nTraffic Lights (TLs) peptides are cell-permeable\, photoswitchable inhibitors specifically developed to target the main adaptor complex of the CME machinery. These peptides\, named TL1 and TL2\, have already proved capable of inhibiting CME in a light-regulated manner when tested in mammalian cells. Here we show that TL peptides retain their activity in yeast. After having confirmed photoregulation of CME events in this extremely versatile eukaryotic model system\, we now aim to achieve in situ activation of the peptide so to directly address the role of endocytosis in cellular processes such as cytokinesis or cell migration.
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-andres-marco-and-davia-prischich-2/
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:20190726T100000
DTEND;TZID=Europe/Madrid:20190726T120000
DTSTAMP:20260505T151727
CREATED:20190722T063239Z
LAST-MODIFIED:20190722T063239Z
UID:67355-1564135200-1564142400@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Ariadna Marin and Ignasi Casanellas
DESCRIPTION:Linking epithelial size\, tension and pressure in curved epithelial monolayers\nAriadna Marin\, Integrative Cell and Tissue Dynamics\nEpithelia are thin cellular layers that act as mechanical and biochemical barriers. They are dynamic tissues that present strong intercellular junctions needed to maintain their integrity while growing and regenerating. During embryogenesis\, they fold progressively and give rise to highly reproducible 3D shapes that guide the shape and positioning of organs. \nThe way pressure and tension depend on the size of 3D epithelial structures can help us understand how epithelia fold into determined shapes and are able to maintain them even under the continuous remodelling due to cell division. In this project we generate simple fluid-filled MDCK 3D monolayers to study the link between epithelial size\, luminal pressure and intercellular tension. \nNanoscale surface adhesiveness continually modulates intercellular communication in cartilage development\nIgnasi Casanellas\, Nanobioengineering\nNanoscale inputs of the extracellular matrix (ECM) affect cell behavior\, including differentiation. We have developed a method for the simple production of large-scale substrates functionalized with cell-adhesive moieties of arginine-glycine-aspartate (RGD) dendrimers\, with uneven local densities at the nanoscale. \nIn the first stages of cartilage formation\, mesenchymal stem cells gather together\, forming condensates with an extensive gap junctional intercellular communication (GJIC) network. The establishment of this communication network is imperative for the development of healthy cartilage tissue. We have used nanopatterned substrates to locally control cell-substrate adherence during mesenchymal condensation\, a prevalent morphogenetic transition\, and promote stem cell differentiation towards chondrogenesis. We here demonstrate that local ligand density defines gap junctional protein Cx43 network architecture and GJ functionality. \nBy a condensate transplantation assay\, we then reveal that differentiating stem cells are sensitive to evolving substrate inputs in a continuous feedback mode after condensation. The renewal of optimal ligand conditions led to a revamp of Cx43 expression. \nThis knowledge provides new insight into cell-matrix nanoscale interactions during morphogenesis. It is relevant for the design of nanopatterned platforms for cell-based regenerative therapies of mesenchymal tissues such as cartilage.
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-ariadna-marin-and-ignasi-casanellas/
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:20190726T100000
DTEND;TZID=Europe/Madrid:20190726T120000
DTSTAMP:20260505T151727
CREATED:20190722T063239Z
LAST-MODIFIED:20190722T063239Z
UID:96487-1564135200-1564142400@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Ariadna Marin and Ignasi Casanellas
DESCRIPTION:Linking epithelial size\, tension and pressure in curved epithelial monolayers\nAriadna Marin\, Integrative Cell and Tissue Dynamics\nEpithelia are thin cellular layers that act as mechanical and biochemical barriers. They are dynamic tissues that present strong intercellular junctions needed to maintain their integrity while growing and regenerating. During embryogenesis\, they fold progressively and give rise to highly reproducible 3D shapes that guide the shape and positioning of organs. \nThe way pressure and tension depend on the size of 3D epithelial structures can help us understand how epithelia fold into determined shapes and are able to maintain them even under the continuous remodelling due to cell division. In this project we generate simple fluid-filled MDCK 3D monolayers to study the link between epithelial size\, luminal pressure and intercellular tension. \nNanoscale surface adhesiveness continually modulates intercellular communication in cartilage development\nIgnasi Casanellas\, Nanobioengineering\nNanoscale inputs of the extracellular matrix (ECM) affect cell behavior\, including differentiation. We have developed a method for the simple production of large-scale substrates functionalized with cell-adhesive moieties of arginine-glycine-aspartate (RGD) dendrimers\, with uneven local densities at the nanoscale. \nIn the first stages of cartilage formation\, mesenchymal stem cells gather together\, forming condensates with an extensive gap junctional intercellular communication (GJIC) network. The establishment of this communication network is imperative for the development of healthy cartilage tissue. We have used nanopatterned substrates to locally control cell-substrate adherence during mesenchymal condensation\, a prevalent morphogenetic transition\, and promote stem cell differentiation towards chondrogenesis. We here demonstrate that local ligand density defines gap junctional protein Cx43 network architecture and GJ functionality. \nBy a condensate transplantation assay\, we then reveal that differentiating stem cells are sensitive to evolving substrate inputs in a continuous feedback mode after condensation. The renewal of optimal ligand conditions led to a revamp of Cx43 expression. \nThis knowledge provides new insight into cell-matrix nanoscale interactions during morphogenesis. It is relevant for the design of nanopatterned platforms for cell-based regenerative therapies of mesenchymal tissues such as cartilage.
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-ariadna-marin-and-ignasi-casanellas-2/
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:20191129T100000
DTEND;TZID=Europe/Madrid:20191129T120000
DTSTAMP:20260505T151727
CREATED:20191125T105531Z
LAST-MODIFIED:20191125T105531Z
UID:96558-1575021600-1575028800@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Ferran Velasco and Fabio Riefolo
DESCRIPTION:Cellulose-based cryogels for long-term culture of pancreatic islets and skeletal muscle tissue\nFerran Velasco\, Biosensors for Bioengineering\nIslet encapsulation inside traditional hydrogels is one of the most common techniques to study insulin secretion for Diabetes Mellitus studies. However\, it’s proved that cells encapsulated in a depth of more than 100 microns die due the lack of nutrient diffusion. As pancreatic islets are spherical aggregations of around 100 microns in diameter\, this problem increases exponentially. To solve this problem\, in this project we propose the use of new Carboxymethyl cellulose – gelatin biocomposite in combination with cryogelation technique to engineer a new in vitro model to mimic the insulin-mediated skeletal muscle glucose metabolism.\nCarboxymethyl cellulose (CMC) is biocompatible\, but not mammalian cell-degradable and shows extraordinary elasticity features. Gelatin is able to provide the 3D microenvironment for the proliferation of different cell types and cell-interactive biological activity\, very desirable properties for muscle and pancreas tissue scaffold. Cryogelation technique consists in freezing a prepolymer solution at sub-zero temperatures\, so water-ice crystals are formed while the material crosslinks. When it’s defrosted\, these water-ice crystals lead to “empty” cavities that forms a macroporous and very interconnected scaffold that fits with our needs of morphology and nutrient diffusion. \nWe first optimize the protocol to achieve the desired morphology; for the pancreatic tissue we achieved a random porosity with high interconnected pores and for the skeletal muscle we fabricate it with an anisotropic structure. We characterize it by stiffness\, pore distribution\, SEM images and swelling to know its mechanical properties. Then we seed cells in the specific cryogel to characterize its biological behavior depending the cryogel approach used. \nOur results are promising for seeding both cell types\, as the morphology and pore distributions fits with our needs. These scaffolds show higher nutrient diffusion\, good material properties and a better manipulation compared to traditional hydrogels for these tissues. \nPhotocontrol of Muscarinic Receptors and Applications In Vivo\nFabio Riefolo\, Nanoprobes and Nanoswitches\nRemote control of physiological functions with light offers the promise of unveiling their complex spatiotemporal dynamics in vivo\, and enabling highly focalized therapeutic interventions with reduced systemic toxicity. Optogenetic methods have been implemented in the heart\, but the need of genetic manipulation jeopardizes clinical applicability. We present a method to modulate cardiac function with light through a photoswitchable compound and without genetic manipulation. A new light-regulated drug\, named PAI\, was designed and synthesized to be active on M2 muscarinic acetylcholine receptor (mAChR). PAI can be reversibly photoisomerized between cis and trans conformations under UV and visible light and is able to photocontrol the activation M2 mAChRs in vitro. \nWe show that PAI has different light-dependent cardiac effects in a mammalian animal model. Finally\, we demonstrate the reversible\, real-time photocontrol of cardiac function in translucent wildtype tadpoles: PAI induced bradycardia and this effect could be reversibly switched using UV and visible illumination. PAI can also effectively activate M2 receptors using two-photon excitation with near-infrared light\, which overcomes the scattering and low penetration of short-wavelength illumination. Such a new approach may enable enhanced spatial and temporal selectivity for cardiovascular drugs.
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-ferran-velasco-and-fabio-riefolo-2/
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:20191129T100000
DTEND;TZID=Europe/Madrid:20191129T120000
DTSTAMP:20260505T151727
CREATED:20191125T105531Z
LAST-MODIFIED:20191125T105531Z
UID:69646-1575021600-1575028800@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Ferran Velasco and Fabio Riefolo
DESCRIPTION:Cellulose-based cryogels for long-term culture of pancreatic islets and skeletal muscle tissue\nFerran Velasco\, Biosensors for Bioengineering\nIslet encapsulation inside traditional hydrogels is one of the most common techniques to study insulin secretion for Diabetes Mellitus studies. However\, it’s proved that cells encapsulated in a depth of more than 100 microns die due the lack of nutrient diffusion. As pancreatic islets are spherical aggregations of around 100 microns in diameter\, this problem increases exponentially. To solve this problem\, in this project we propose the use of new Carboxymethyl cellulose – gelatin biocomposite in combination with cryogelation technique to engineer a new in vitro model to mimic the insulin-mediated skeletal muscle glucose metabolism.\nCarboxymethyl cellulose (CMC) is biocompatible\, but not mammalian cell-degradable and shows extraordinary elasticity features. Gelatin is able to provide the 3D microenvironment for the proliferation of different cell types and cell-interactive biological activity\, very desirable properties for muscle and pancreas tissue scaffold. Cryogelation technique consists in freezing a prepolymer solution at sub-zero temperatures\, so water-ice crystals are formed while the material crosslinks. When it’s defrosted\, these water-ice crystals lead to “empty” cavities that forms a macroporous and very interconnected scaffold that fits with our needs of morphology and nutrient diffusion. \nWe first optimize the protocol to achieve the desired morphology; for the pancreatic tissue we achieved a random porosity with high interconnected pores and for the skeletal muscle we fabricate it with an anisotropic structure. We characterize it by stiffness\, pore distribution\, SEM images and swelling to know its mechanical properties. Then we seed cells in the specific cryogel to characterize its biological behavior depending the cryogel approach used. \nOur results are promising for seeding both cell types\, as the morphology and pore distributions fits with our needs. These scaffolds show higher nutrient diffusion\, good material properties and a better manipulation compared to traditional hydrogels for these tissues. \nPhotocontrol of Muscarinic Receptors and Applications In Vivo\nFabio Riefolo\, Nanoprobes and Nanoswitches\nRemote control of physiological functions with light offers the promise of unveiling their complex spatiotemporal dynamics in vivo\, and enabling highly focalized therapeutic interventions with reduced systemic toxicity. Optogenetic methods have been implemented in the heart\, but the need of genetic manipulation jeopardizes clinical applicability. We present a method to modulate cardiac function with light through a photoswitchable compound and without genetic manipulation. A new light-regulated drug\, named PAI\, was designed and synthesized to be active on M2 muscarinic acetylcholine receptor (mAChR). PAI can be reversibly photoisomerized between cis and trans conformations under UV and visible light and is able to photocontrol the activation M2 mAChRs in vitro. \nWe show that PAI has different light-dependent cardiac effects in a mammalian animal model. Finally\, we demonstrate the reversible\, real-time photocontrol of cardiac function in translucent wildtype tadpoles: PAI induced bradycardia and this effect could be reversibly switched using UV and visible illumination. PAI can also effectively activate M2 receptors using two-photon excitation with near-infrared light\, which overcomes the scattering and low penetration of short-wavelength illumination. Such a new approach may enable enhanced spatial and temporal selectivity for cardiovascular drugs.
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-ferran-velasco-and-fabio-riefolo/
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:20191213T003000
DTEND;TZID=Europe/Madrid:20191213T140000
DTSTAMP:20260505T151727
CREATED:20191203T100159Z
LAST-MODIFIED:20191210T093127Z
UID:69736-1576197000-1576245600@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Maria Arista
DESCRIPTION:Super-resolution microscopy for understanding the formation and inhibition of influenza virus structures\nMaria Arista\, Nanoscopy for Nanomedicine\nSuper-resolution microscopy is a mighty tool that has the ability to study fluorescence samples beyond the diffraction limit\, achieving a spatial resolution around 20 nm. The study of viruses can greatly benefit from super-resolution imaging\, mainly due to their small size\, between 50 and 200 nm. Here we show that\, thanks to this technique\, we are able to visualize and study two relevant viral structures: filaments of influenza virus using stochastic optical construction microscopy (STORM) and virus-like particles formed from influenza using DNAPAINT (Points accumulation for imaging in nanoscale topography) .\nInfluenza A virus is highly pleomorphic\, and virions can have either spherical or filamentous morphology. Influenza A virus strain A/Udorn/72 (H3N2) produces copious amounts of long and thin filaments on the surface of infected cells\, led mainly by the matrix protein M1 and the membrane protein M2. These filaments are strongly related to the infectivity of influenza and cell-to-cell communication\, however\, due to the small size of these filaments (200 nm of width)\, they are hard to characterize in detail using immunofluorescence microscopy. \nHere\, we show with super-resolution microscopy that filament formation was inhibited by the treatment of cells with specific IgG2a and IgG1 antibodies but was not inhibited with the isotype control antibodies. Our results demonstrate that M2e-specific IgGs reduces the level influenza A virus replication in vitro and suggest that the inhibition of virus replication lead by M2especific antibodies is due to the fragmentation of filamentous virions and the loss of filament formation from the surfaces of infected cells.\nMoreover\, we study virus-like particles produced from influenza proteins transfected on mammalian cells. These structures mimic viruses but they lack viral genetic material\, for this reason they are great models to study influenza particles without risks. Influenza expresses 3 different proteins on the surface of the particle and the distribution and homogeneity between particles is not well understood. To study this distribution\, we are analyzing with DNA-PAINT the differential expression and distribution of these 3 proteins on the surface of the particles. Overall we show how super-resolution is suitable to study nanoscale viral structures and can provide new insights into anti-viral therapies. \n 
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-maria-arista-and-xarxa-quiroga/
LOCATION:IBEC\, floor 11\, Tower I\, Baldiri Reixac 4-8\, 08028 Barcelona\, Spain
CATEGORIES:PhD Discussions Session
ORGANIZER;CN="IBEC":MAILTO:www.ibecbarcelona.eu
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20191213T003000
DTEND;TZID=Europe/Madrid:20191213T140000
DTSTAMP:20260505T151727
CREATED:20191203T100159Z
LAST-MODIFIED:20191203T100159Z
UID:96567-1576197000-1576245600@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Maria Arista
DESCRIPTION:Super-resolution microscopy for understanding the formation and inhibition of influenza virus structures\nMaria Arista\, Nanoscopy for Nanomedicine\nSuper-resolution microscopy is a mighty tool that has the ability to study fluorescence samples beyond the diffraction limit\, achieving a spatial resolution around 20 nm. The study of viruses can greatly benefit from super-resolution imaging\, mainly due to their small size\, between 50 and 200 nm. Here we show that\, thanks to this technique\, we are able to visualize and study two relevant viral structures: filaments of influenza virus using stochastic optical construction microscopy (STORM) and virus-like particles formed from influenza using DNAPAINT (Points accumulation for imaging in nanoscale topography) .\nInfluenza A virus is highly pleomorphic\, and virions can have either spherical or filamentous morphology. Influenza A virus strain A/Udorn/72 (H3N2) produces copious amounts of long and thin filaments on the surface of infected cells\, led mainly by the matrix protein M1 and the membrane protein M2. These filaments are strongly related to the infectivity of influenza and cell-to-cell communication\, however\, due to the small size of these filaments (200 nm of width)\, they are hard to characterize in detail using immunofluorescence microscopy. \nHere\, we show with super-resolution microscopy that filament formation was inhibited by the treatment of cells with specific IgG2a and IgG1 antibodies but was not inhibited with the isotype control antibodies. Our results demonstrate that M2e-specific IgGs reduces the level influenza A virus replication in vitro and suggest that the inhibition of virus replication lead by M2especific antibodies is due to the fragmentation of filamentous virions and the loss of filament formation from the surfaces of infected cells.\nMoreover\, we study virus-like particles produced from influenza proteins transfected on mammalian cells. These structures mimic viruses but they lack viral genetic material\, for this reason they are great models to study influenza particles without risks. Influenza expresses 3 different proteins on the surface of the particle and the distribution and homogeneity between particles is not well understood. To study this distribution\, we are analyzing with DNA-PAINT the differential expression and distribution of these 3 proteins on the surface of the particles. Overall we show how super-resolution is suitable to study nanoscale viral structures and can provide new insights into anti-viral therapies. \n 
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-maria-arista-and-xarxa-quiroga-2/
LOCATION:IBEC\, floor 11\, Tower I\, Baldiri Reixac 4-8\, 08028 Barcelona\, Spain
CATEGORIES:PhD Discussions Session
ORGANIZER;CN="IBEC":MAILTO:www.ibecbarcelona.eu
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20200228T100000
DTEND;TZID=Europe/Madrid:20200228T120000
DTSTAMP:20260505T151727
CREATED:20200221T110843Z
LAST-MODIFIED:20200221T110843Z
UID:71615-1582884000-1582891200@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Xarxa Quiroga and Adrián López
DESCRIPTION:Biochemical responses to cell membrane mechanical remodelling\nXarxa Quiroga\, Cellular and molecular mechanobiology\nIn a range of physiological processes\, from extravasation to endocytosis\, cells are constantly submitted to morphological changes\, which eventually entail plasma membrane reshaping and adaptation. This remodelling could be harnessed by cells to detect and respond to shape changes\, enabling mechanosensing mechanisms. However\, how this occurs is still largely unknown.\nTo increase our understanding on how such process can happen\, we have engineered a cell-stretching system that allows us to induce controlled plasma membrane remodelling while monitoring the whole process with the help of a microscope.\nBy using this set up\, we have found that cell de-stretch triggers the formation of transient membrane evaginations whose resorption is actively regulated by BAR protein recruitment and actin polymerisation. The described process may be the first part of a molecular cascade used by cells in response to stretch. \n\nDevelopment of Microphysiological Systems for the Evaluation of Regenerative Therapies\nAdrián López\, Biomaterials for Regenerative Therapies\nThe modelling of human organs has long been a task for scientist in order to lower the costs of therapeutic development and understand the pathological onset of human disease. Animal models remain the gold standard for drug discovery\, despite their widely recognized limitations such as their marked differences with humans in terms of genetics and etiology or their high cost. \nDuring the last decade\, the advancements in tissue engineering and microfabrication gave rise to innovative models known as organs-on-a-chip or microphysiological systems\, which aim to build functional miniaturized tissues in vitro that closely mimic the actual in vivo microenvironment. In this work\, we will present two microphysiological platforms that we are developing with the goal of understanding and evaluating biomaterial-based regenerative therapies. The first model is aimed at replicating the bone healing microenvironment to evaluate the angiogenic potential of calcium-releasing scaffolds. The second model will be focused on the generation of an ischemic injury on a physiologically relevant cardiac tissue to test if lactate-releasing scaffolds are able to stimulate cardiac tissue regeneration.
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-xarxa-quiroga-and-adrian-lopez/
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:20200228T100000
DTEND;TZID=Europe/Madrid:20200228T120000
DTSTAMP:20260505T151727
CREATED:20200221T110843Z
LAST-MODIFIED:20200221T110843Z
UID:96627-1582884000-1582891200@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Xarxa Quiroga and Adrián López
DESCRIPTION:Biochemical responses to cell membrane mechanical remodelling\nXarxa Quiroga\, Cellular and molecular mechanobiology\nIn a range of physiological processes\, from extravasation to endocytosis\, cells are constantly submitted to morphological changes\, which eventually entail plasma membrane reshaping and adaptation. This remodelling could be harnessed by cells to detect and respond to shape changes\, enabling mechanosensing mechanisms. However\, how this occurs is still largely unknown.\nTo increase our understanding on how such process can happen\, we have engineered a cell-stretching system that allows us to induce controlled plasma membrane remodelling while monitoring the whole process with the help of a microscope.\nBy using this set up\, we have found that cell de-stretch triggers the formation of transient membrane evaginations whose resorption is actively regulated by BAR protein recruitment and actin polymerisation. The described process may be the first part of a molecular cascade used by cells in response to stretch. \n\nDevelopment of Microphysiological Systems for the Evaluation of Regenerative Therapies\nAdrián López\, Biomaterials for Regenerative Therapies\nThe modelling of human organs has long been a task for scientist in order to lower the costs of therapeutic development and understand the pathological onset of human disease. Animal models remain the gold standard for drug discovery\, despite their widely recognized limitations such as their marked differences with humans in terms of genetics and etiology or their high cost. \nDuring the last decade\, the advancements in tissue engineering and microfabrication gave rise to innovative models known as organs-on-a-chip or microphysiological systems\, which aim to build functional miniaturized tissues in vitro that closely mimic the actual in vivo microenvironment. In this work\, we will present two microphysiological platforms that we are developing with the goal of understanding and evaluating biomaterial-based regenerative therapies. The first model is aimed at replicating the bone healing microenvironment to evaluate the angiogenic potential of calcium-releasing scaffolds. The second model will be focused on the generation of an ischemic injury on a physiologically relevant cardiac tissue to test if lactate-releasing scaffolds are able to stimulate cardiac tissue regeneration.
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-xarxa-quiroga-and-adrian-lopez-2/
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:20201211T100000
DTEND;TZID=Europe/Madrid:20201211T120000
DTSTAMP:20260505T151727
CREATED:20201116T151624Z
LAST-MODIFIED:20201130T163347Z
UID:79742-1607680800-1607688000@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Nimesh Ramesh and Sock Ching Low
DESCRIPTION:Microfluidic device for engineering 3D epithelial monolayers with controlled pressure\nNimesh Ramesh\, Integrative Cell and Tissue Dynamics \nThe remarkable feature of the epithelial sheets is to form specialized 3D structures suited to their physiological roles\, such as highly branched structures in the lungs\, drastic shape changes during embryonic development\, or self-organizing organoids. These tissues are distinctive not just in the forms cells assume\, but also in function. To achieve this\, tissues and the cells in them exhibit coordinated behavior across the spatial and temporal scale. In a sense\, 3D epithelia resemble an active material that adapts and changes in response to its biophysical-chemical stimuli like gene expression\, morphogen gradients\, and lumen pressure. A rheological study of the epithelia would provide unique insight on two fronts. First\, to understand the fundamental physical rules of the biology\, and second for inspiration of new engineering tools and design principles. \nOur study focuses on the tissue response to physical forces\, specifically pressure\, tension\, and curvature. We have fabricated a microfluidic setup to subject epithelial tissues to lumen pressure at different spatial and temporal scales. The epithelial monolayer is grown on a porous surface with circular low adhesion zones. On applying controlled pressure\, the monolayer delaminates into a spherical cap (dome). Laplace law for spherical shells allows us to compute tension in the 3D structure with applied pressure and the radius of the dome. \nThis microfluidic device helps us to characterize the 3D epithelial shape along with the mapping of physical forces. Here\, we demonstrate that the device can subject MDCK epithelial cells to a range of lumen pressure at different rates. Drastic reduction in pressure results in tissue collapsing into wrinkles; showing buckling tendency of the tissue under compression. We think that our device enables studying geometrical and biophysical constraints of tissues and unravel emergent phenomena in tissues. \n\nSaccade rate is associated with number of items in working memory\nSock Shing Low\, Synthetic\, Perceptive\, Emotive and Cognitive Systems (SPECS) \nWorking memory has been shown to rely on theta oscillations for item representations\, and the successful recall of items depends greatly on theta’s phase during both encoding and recall. At the same time\, it has been observed that saccadic eye movements during visual exploration trigger theta phase-resets\, raising the question of whether the neuronal substrates of mnemonic processing rely on motor-evoked responses. To quantify the relationship between saccadic eye movements and working memory load\, we tested human participants performing an n-back Sternberg auditory task in combination with a colour-based catch detection task. We observed a task-specific interference in performance and an increase in saccade rate when both tasks were carried out simultaneously. Saccade rate also increased concurrently with working memory load in the Sternberg task’s pre-response stage\, reflecting its hypothesised role in memory recall. Our results suggest an interplay between saccades and hippocampal theta during retrieval of items in working memory. \nThe PhD discussions session will be held ONLINE at the GoToMeeting platform
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-nimesh-ramesh-and-sock-ching-low/
CATEGORIES:PhD Discussions Session
ORGANIZER;CN="IBEC":MAILTO:www.ibecbarcelona.eu
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20210129T100000
DTEND;TZID=Europe/Madrid:20210129T120000
DTSTAMP:20260505T151727
CREATED:20210107T102348Z
LAST-MODIFIED:20210125T074321Z
UID:80732-1611914400-1611921600@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Gerard Rubí and Ignasi Ferrer
DESCRIPTION:Development of an in vitro three-dimensional colorectal tumor model for drug screening\nGerard Rubí\, Biomaterials for Regenerative Therapies \nThe majority of morphogenetic and pathological processes are driven by cells responding to the surrounding matrix cues\, including matrix composition\, architecture\, and mechanical properties. Despite the increased evidence of extracellular matrix (ECM) properties\, in vitro substitutes still fail to effectively mimic the native microenvironment. In this study\, we aim to develop and characterize cell-derived extracellular matrices (CDMs) obtained through a protein deposition from human mesenchymal stem cells cultured in sacrificial 3D scaffold templates of poly-lactic acid (PLA) microcarriers. Obtained decellularized CDMs closely mimic biochemical\, physical\, and mechanical properties of native tissues’ ECM. The produced novel CDMs\, are currently tested as a 3D cell culture platform for disease modelling. This is achieved through CDMs repopulation with colorectal cancer cells and cancer associated fibroblasts (CAFs). The new 3D CDMs-cancer platform will provide an in vitro tumor model to study the cells-ECM interactions and potential therapeutic targets\, to finally serve as a drug-screening platform for personalized medicine. \nNovel m-Health and multimodal physiological biomarkers for non-invasive monitoring and home healthcare of Obstructive Sleep Apnea and COPD patients with comorbidities\nIgnasi Ferrer\, Biomedical Signal Processing and Interpretation \nObstructive sleep apnea (OSA) is a sleep disorder in which repetitive upper airway obstructive events occur during sleep. These events can induce hypoxia\, which is a risk factor for multiple cardiovascular and cerebrovascular diseases. OSA is also known to be position-dependent in some patients\, which is referred to as positional OSA (pOSA). The gold-standard technique for diagnosing OSA is nocturnal polysomnography (PSG)\, which consists in recording multiple physiological signals while the patient is asleep in a hospital sleep lab. However\, PSG has some important limitations\, such as the high cost of the diagnostic test; the diagnosis is usually performed with a one-night sleep assessment\, which does not account for the variability of sleep performance in the patient; and the sleep quality varies from that at home\, because the patient has to sleep in a different bed connected to a lot of electrodes and wires. \nIn this study we aim to study how smartphones could be used to diagnose and monitor sleep apnea at home. Since smartphones are worldwide available devices\, with a lot of embedded sensors\, they appear as a feasible mHealth tools that could help overcome these limitations. \nThe PhD discussions session will be held ONLINE at the GoToMeeting platform
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-gerard-rubi-and-ignasi-ferrer/
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20210326T100000
DTEND;TZID=Europe/Madrid:20210326T120000
DTSTAMP:20260505T151727
CREATED:20210315T105812Z
LAST-MODIFIED:20210315T105812Z
UID:82816-1616752800-1616760000@ibecbarcelona.eu
SUMMARY:PhD Discussions Sessions: Héctor López Carral
DESCRIPTION:Subjective ratings of emotive stimuli predict the impact of the COVID-19 quarantine on affective states\nHéctor López Carral\, SPECS lab\, IBEC \nThe COVID-19 crisis resulted in a large proportion of the world’s population having to employ social distancing measures and self-quarantine. Given that limiting social interaction impacts mental health\, we assessed the effects of quarantine on emotive perception as a proxy of affective states. To this end\, we conducted an online experiment whereby 112 participants provided affective ratings for a set of normative images and reported on their well-being during COVID-19 self-isolation. We found that current valence ratings were significantly lower than the original ones from 2015. This negative shift correlated with key aspects of the personal situation during the confinement\, including working and living status\, and subjective well-being. These findings indicate that quarantine impacts mood negatively\, resulting in a negatively biased perception of emotive stimuli. Moreover\, our online assessment method shows its validity for large-scale population studies on the impact of COVID-19 related mitigation methods and well-being. \nThe PhD discussions session will be held ONLINE at the GoToMeeting platform
URL:https://ibecbarcelona.eu/event/phd-discussions-sessions-hector-lopez-carral/
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20210430T100000
DTEND;TZID=Europe/Madrid:20210430T120000
DTSTAMP:20260505T151727
CREATED:20210419T121756Z
LAST-MODIFIED:20210420T103321Z
UID:83514-1619776800-1619784000@ibecbarcelona.eu
SUMMARY:PhD Discussion Sessions: Teodora Andrian and Xavier Arqué
DESCRIPTION:Correlating super-resolution microscopy and transmission electron microscopy for nanoparticle characterisation\nTeodora Andrian\, Nanoscopy for nanomedicine group \nThe functionalization of nanoparticles with surface functional moieties is a key strategy to achieve bioactivity and cell targeting in nanomedicine. The interplay between size and ligand number and distribution is crucial for the formulation performance and needs to be properly characterized to understand nanoparticle structure-activity relations. However\, the particle-to-particle heterogeneity poses a serious challenge due to the lack of methods able to measure both size and ligand number and distribution at the same time and at the single particle level. Here we address this issue by introducing a correlative method combining super-resolution microscopy (SRM) and transmission electron microscopy (TEM) imaging. Correlative light and electron microscopy (CLEM) techniques proved their potential in structural biology but to the best of our knowledge\, they have not yet been explored for the structural characterization of nanoparticles. Here we apply our super-resCLEM method to characterize the relationship between size and ligand number\, and ligand density in PLGA-PEG nanoparticles at the single particle and single-molecule level.  We highlight how heterogeneity found in nanoparticle size can impact ligand distribution\, and we discuss the implications on formulation performance. We show how a significant part of the nanoparticle population goes completely undetected in the single-technique analysis\, demonstrating that the characterization of nanomaterials using a multiparametric correlative method outplays the information obtained compared to a one-method-at-a-time approach. Using SRM alone\, we demonstrated how PEG architecture can influence ligand conjugation efficiency and accessibility. The applicability of our method spans beyond PLGA-PEG nanoparticles and holds great promise for the multiparametric analysis of several other parameters and nanomaterials. \nUnraveling the fundamental aspects of enzyme-powered micromotors\nXavier Arqué\, Smart Nano-Bio-Devices group \nEnzyme-coated micro- and nanomotors self-propel by the biocatalytic conversion of substrates into products and show great promise as actively navigating agents in the fields of biomedicine and environmental applications. However\, many of the fundamental aspects underlying enzyme-powered self-propulsion have yet to be fully understood and are crucial for their optimal implementation. Under this framework\, this research is focused on elucidating and studying the intrinsic (catalytic turnover or structural flexibility) and extrinsic (bulk and local ionic media) enzymatic properties that lead to an improved active motion powered by bio-catalysis. This is enabled by exploring novel types of both i) enzymes that can act as active motion engines and ii) platforms with appealing properties to be used as chassis of enzymatic micro- and nanomotors. Overall\, this work contributes to a better understanding of the mechanism of motion of enzymatic active motion\, expands the current library of enzymatic engines and chassis materials available\, and provides new insights into the feasibility of implementation of enzyme-powered micro- and nanomotors. \nThe session will be held online using the GoToMeeting Platform
URL:https://ibecbarcelona.eu/event/phd-discussion-sessions-teodora-andrian-and-xavier-arque/
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20210702T100000
DTEND;TZID=Europe/Madrid:20210702T120000
DTSTAMP:20260505T151727
CREATED:20210628T090118Z
LAST-MODIFIED:20210629T084516Z
UID:85634-1625220000-1625227200@ibecbarcelona.eu
SUMMARY:PhD Discussions: Ignasi Granero
DESCRIPTION:Ignasi Granero\, Celular and molecular mechanobiology group \nIn eukaryotic cells\, the cell nucleus contains the DNA and directs the reaction to important signalling cascades\, both biochemical and biomechanical. At the Cellular and Molecular Mechanobiology lab we study how forces and the physical characteristics of the cell environment affect cell behaviour and homeostasis. In my case\, I am interested in how the cell nucleus senses physical changes and triggers a cell response to them.\nFor this purpose\, we have engineered a battery of fluorescent proteins\, which change their location depending on the physical state of the nucleus. Higher forces in the nucleus correspond with higher nuclear accumulation of these proteins. Indicating that these proteins react to mechanical/morphological stimuli. Then\, we have chosen the variant that can be used as a mechano-sensor. Currently\, we are testing the sensor in single- and multi-cell approaches to understand its behaviour in different systems and the ruling principles under its functioning. \nThis PhD Discussion will be held online using the GoToMeeting app
URL:https://ibecbarcelona.eu/event/phd-discussions-ignasi-granero/
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20211126T100000
DTEND;TZID=Europe/Madrid:20211126T120000
DTSTAMP:20260505T151727
CREATED:20210909T094150Z
LAST-MODIFIED:20211117T150528Z
UID:87087-1637920800-1637928000@ibecbarcelona.eu
SUMMARY:PhD Discussions: Yolanda Castillo and Marc Molina
DESCRIPTION:Assessment of trunk function in patients with spinal cord injury using electromyography and smartphone accelerometry\nYolanda Castillo\, Biomedical Signal Processing and Interpretation \nSpinal cord injury (SCI) causes motor and sensory impairment below the level of the injury\, but also many other health problems. A common consequence of SCI is the lack of control over trunk muscles\, leading to deficits in postural control and balance while sitting. Since trunk stability is essential to maintain upright posture and support functional movements\, impaired trunk function constitutes a major cause of motor disability in SCI patients\, limiting their independence and quality of life. However\, trunk stability is rarely examined in studies of mobility after SCI\, and one of the reasons is the lack of quantitative measures for assessing trunk function. Here we propose to record and analyze electromyographic (EMG) and smartphone accelerometric data to extract quantitative measures for the evaluation of trunk function. Our aims were: 1) to characterize muscle activity and movement patterns of trunk flexion during a reaching task in healthy subjects and patients with SCI\, 2) to compare the impact of cervical and thoracic injuries in trunk function\, and 3) to investigate the potentially destabilizing effects of a startling acoustic stimulus in this task. For these purposes\, during a reaching movement requiring trunk flexion\, we recorded the EMG activity of 8 trunk\, neck\, and shoulder muscles and smartphone accelerometer data from individuals with cervical SCI\, thoracic SCI\, and healthy control subjects. We analyzed these signals and extracted different features\, including the response time until pressing a target button\, EMG onset latencies and amplitudes\, and trunk tilt\, lateral deviation\, and other movement features from accelerometry. The proposed outcome measures revealed deficits in postural control and compensatory strategies employed by SCI patients\, including delayed responses and higher lateral deviations\, which might have important consequences for rehabilitation. The combination of EMG and smartphone accelerometer data can help to develop more suitable methods for the assessment of trunk function in individuals with SCI\, thus improving the follow-up and management of these patients. \nDevelopment of a model of “macro” substrates for the analysis of 3D chromatin structure and transcriptional profiling\nMarc Molina\, Cellular and Molecular Mechanobiology \nMechanically-induced changes in the genome are increasingly recognized as major drivers of cell and tissue function. However\, current and past studies on this topic in vitro have often been limited by the sample size required for these genomic analyses. Here we describe the development of a polyacrylamide gel (pAAg) substrate with larger area than gels previously generated in labs worldwide. These substrates display the same tunable stiffness as their smaller counterparts and are particularly suitable to accommodate large numbers of cells. We tested the substrates to assess the effect that changes in rigidity have in the cell’s genome\, both at the level of chromatin organization and transcriptional regulation. For this\, two different rigidities were used (soft vs stiff) with three conditions which included: i) a control group\, ii) a transiently expressing mutant of RanQ69L that prevents all nucleocytoplasmic transport and iii) a transiently expressing mutant of NES1-KASH that prevents force transmission to the nucleus. Our preliminary results suggest that cells seeded on pAAg substrates of different rigidities display differences in chromatin structure and gene expression\, but more data will be necessary to further support these results. Ultimately\, the aim of our project is to understand down the road how changes in rigidity affect: i) the 3D structure and interaction map of chromatin and ii) the activated or repressed transcriptional programs in soft and stiff substrates. Overall\, this new model will help us to characterize how the genome is affected by rigidity both at the structural and transcriptional levels. More broadly\, we expect the potential findings of this work to help the community detailing the effect of changes in tissue stiffness in the genome spatial organization. \nThis PhD Discussion will be hybrid. Yolanda Castillo will be doing her presentation online and Marc from the Baobab room\, located in tower I floor 11. To follow the session online\, find here the link\, we will be using the GoToMeeting app. If you wish to attend in person\, the free spots will be assigned on a first come first served basis\, the capacity of the room is for 30 people.
URL:https://ibecbarcelona.eu/event/phd-discussions-yolanda-castillo-and-marc-molina/
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20211217T100000
DTEND;TZID=Europe/Madrid:20211217T120000
DTSTAMP:20260505T151727
CREATED:20210909T094506Z
LAST-MODIFIED:20211209T122951Z
UID:87091-1639735200-1639742400@ibecbarcelona.eu
SUMMARY:PhD Discussions: Enrico Almici and Albert Manzano
DESCRIPTION:Investigating Pathological Extracellular Matrix Architecture\nThe composition and architecture of the extracellular matrix (ECM)\, and their dynamic alterations\, play an important regulatory role on numerous cellular processes. Furthermore\, structural and biochemical properties of the ECM are central in regulating cell behavior via mechanical\, chemical and topological cues detected by receptors in the cell membrane which induce cytoskeleton rearrangement and/or cell nucleus gene expression. Indeed\, distinct ECM architectures are encountered in the native stroma\, which depend on tissue type\, function and composition. For instance\, ECM anisotropy and stiffness are associated with altered ECM degradation and remodeling in cancer. In turn\, this architecture favors tumor progression and invasion. Moreover\, numerous diseases are associated with mutations in genes encoding ECM components\, leading to deficient mechanical properties and altered ECM structure. Thus\, there is an increasing interest to exploit and consolidate this knowledge to improve patients’ treatment and care. In my work I focused on Collagen-VI related muscular dystrophies and Non-small cell lung cancer\, to investigate in vitro and in patient tissues ECM-related biomarkers to be implemented in clinical setting. I employed automatic image segmentation to quantify fibrillar characteristics and investigate the association with the clinicopathological information from patients. Ultimately this analysis along with the tools presented is promising for addressing the need of novel descriptors\, to stratify patients and evaluate their response to experimental treatments. \nEnrico Almici\, Nanobioengineering \nPersonalizing pediatric leukemia treatment using cell-based functional assays and microfluidics\nCancer personalized medicine improves treatment by testing different drugs in samples from every individual patient to select the best option in every case\, maximizing efficacy and reducing side effects. Pediatric B-cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) has an acceptable cure rate\, however\, almost 10% of the cases are refractory to standard-of-care treatments\, showing an urgent need for new therapeutic options. Here\, we use Dynamic BH3 Profiling (DBP)\, a new assay that uses synthetic peptides mimicking the pro-apoptotic effect of the BH3 family of proteins\, to predict treatment efficacy and anti-apoptotic adaptations conferring treatment resistance. Applying DBP in two BCP-ALL cell lines we identified new treatment options including both targeted agents and chemotherapies. We were also able to describe the mechanistic response of these cells after treatment\, which acquired resistance using anti-apoptotic proteins that were later overcome using specific inhibitors called BH3 mimetics. Importantly\, this resistance mechanism was also seen in patient-derived xenografts opening the use of these new combinations with BH3 mimetics in BCP-ALL patients. In the second part of the presentation\, we developed a new version of the DBP protocol. Actual cytometry-based DBP requires a large number of viable cells which are easily obtained in liquid tumors but not in solid tumor biopsies\, limiting the number of treatments that can be explored. To solve this problem\, we developed a microfluidic-based DBP that drastically reduces cell requirement to perform the assay and helps to automatize the process to be implemented as a routinely clinical technique. We validated this microfluidic-based DBP using two gastrointestinal stromal tumor (GIST) cell lines obtaining similar results between the new protocol and the cytometry-based DBP. Finally\, we used a primary GIST sample to identify a treatment combination that induced apoptosis to these patient cells\, which proves that the microfluidic-based DBP can help to personalize solid cancers treatment. \nAlbert Manzano\, Nanobioengineering \nThis PhD Discussion session will be held at Tower I\, 11th floor Baobab room\, there will be 30 avialable seats\, the free spots will be assigned on a first come first served basis.
URL:https://ibecbarcelona.eu/event/phd-discussions-enrico-almici-and-giulia-fornabaio/
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20220225T100000
DTEND;TZID=Europe/Madrid:20220225T170000
DTSTAMP:20260505T151727
CREATED:20220427T110714Z
LAST-MODIFIED:20220503T142126Z
UID:93902-1645783200-1645808400@ibecbarcelona.eu
SUMMARY:PhD Discussions: Giulia Fornabaio and Shubham Tanwar
DESCRIPTION:Biomechanics of the progression of colorectal carcinomas\n\n\n\nGiulia Fornabaio\, Synthetic morphogenesis group \n\n\n\nAccording to the World Health Organization\, cancer is one of the main causes of death worldwide\, with colorectal carcinoma (CRC) being the second-leading cause of tumour related-death. The high rate of mortality of CRCs is principally attributed to the metastasis of neoplastic cells from the primary tumour to secondary organs such as the liver\, the lung and the peritoneum. These cells can disseminate either as single isolated cells or as collective clusters\, undergoing a series of molecular and cellular changes commonly known as Epithelial to Mesenchymal Transition (EMT). However\, in 2018\, Jaulin and her team described a novel modality of peritoneal metastatic spread characterized by the presence of large clusters of cancer cells\, which maintain their epithelial properties and display an outward apical polarity. These clusters of cells\, termed tumour spheres with inverted polarity (TSIPs)\, were found in peritoneal effusions of CRCs patients showing early KRAS mutation and hypermethylation of CpG Islands. \n\n\n\nTSIPs originate through a series of morphological changes: the first event is the sprouting of hypermethylated epithelia\, followed by their apical budding\, leading to the formation of rounded spherical clusters of cells called buds\, and the subsequent cleavage of the newly formed spheres. How cell and tissue mechanics drive this process is still unclear. To provide novel insights into this metastatic cascade\, our project aims at deciphering the biomechanical and cellular events regulating the formation of buds in colorectal cancer cell lines. Employing a combination between cellular biology techniques with biophysical methods\, we showed that this process is characterized by over-proliferation and local changes in cell adhesion\, coupled with the formation of cellular vortexes surrounding the buds. Our study demonstrates that buds development in colorectal carcinomas epithelia is governed by morphological transitions occurring entirely at multicellular level\, rather than by single cells aggregation or cell extrusion. \n\n\n\nImaging Functional Organic Bioelectronic Platforms at the Nanoscale\n\n\n\nShubham Tanwar\, Nanoscale Bioelectrical Characterization group \n\n\n\nIn recent years\, many organic bioelectronic platforms have emerged to bridge the signaling gap between biology and technology. Organic bioelectronic platforms based on transistor architecture\, commonly known as Electrolyte-Gated Transistors (EGTs)\, are an excellent tool to selectively sense\, record\, and monitor biological signals and states\, and convert them into measurable electrical signals.1 Biological events happening at the nanoscale are now routinely studied and characterized by a millimeter-sized transistor. However\, it is not well understood how these nanoscale events interact with the transistor’s nanoscale properties leading to a change in their macroscale response. This gap in understanding is purely due to the lack of techniques to image the electrical properties in a liquid environment. Towards this goal\, our group has adapted in-Liquid Scanning Dielectric Microscopy to unravel the inner working of EGTs at the nanoscale.2 Besides apparent topographical changes\, electrical properties\, like conductivity and interfacial capacitance\, and mechanical properties are mapped at the nanoscale in a working transistor in liquid. The vast information extracted has made it possible to correlate the nanoscale processes with the macroscale response\, offering improved understanding and the potential for substantial optimization of bioelectronic devices. \n\n\n\nThis PhD Discussion session will be held at Tower I\, 11th floor Baobab room\, there will be 30 avialable seats\, the free spots will be assigned on a first come first served basis.
URL:https://ibecbarcelona.eu/event/phd-discussions-giulia-fornabaio-and-shubham-tanwar/
LOCATION:IBEC\, floor 11\, Tower i\, Baldiri Reixac 4-8\, Barcelona\, 08028\, Spain
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20220415T100000
DTEND;TZID=Europe/Madrid:20220415T120000
DTSTAMP:20260505T151727
CREATED:20220503T144933Z
LAST-MODIFIED:20230301T140902Z
UID:94020-1650016800-1650024000@ibecbarcelona.eu
SUMMARY:PhD Discussions: Sefora Conti
DESCRIPTION:Mechanical phenotyping of colorectal cancer patient derived organoids based on LGR5 expression\n\n\n\nSefora Conti\, Integrative cell and tissue dynamics group \n\n\n\nColorectal cancer (CRC) tumors are composed by heterogeneous cell populations comprising differentiated cells and a small pool of cancer stem cells (CSCs). The link between cancer cell differentiation states and their metastatic potential has been the focus of extensive investigation\, with some studies pointing to microenvironmentally defined plasticity as a mechanism indispensable for metastasis formation. Another aspect that might be determinant in tumor cells ability to successfully disseminate\, intravasate\, survive in the blood stream\, extravasate\, colonize distant organs and form secondary tumors is their mechanical phenotype. \n\n\n\nAdopting a bottom-up approach\, we performed a broad biophysical characterization of CRC patient derived organoids (PDOs)\, engineered to fluorescently label cells expressing LGR5\, a well-established marker for CSCs. We show that CRC cells differentiation states are associated with distinct biomechanical phenotypes\, with potential repercussions on their metastatic ability. \n\n\n\nAt the single cell level\, LGR5+ cells display a more elongated and polarized shape while the LGR5- cells exhibit higher roundness and a smaller asymmetry in the stress field. LGR5+ are stiffer compared to their differentiated counterparts and more prone to adopt a fast amoeboid-like migration under confinement.  At the molecular level\, cancer stemness is related to differential expression of the ERM protein family\, responsible of tethering the cell membrane to the underlying actin cortex. \n\n\n\nThese distinct mechanical phenotypes translate to different migratory and morphological phenotypes at a cluster level. Clusters expressing high levels of LGR5 showed a more spread and flattened shape compared to more differentiated clusters. Moreover\, LGR5 expression in clusters is negatively correlated with their migration speed and their polarization state. Hence\, clusters containing more differentiated cells migrate faster\, display higher roundness and higher polarization state. \n\n\n\nAt higher complexity levels\, such as interactions with endothelial cells\, LGR5 expression in CRC clusters affects their ability to adhere to an endothelial monolayer and form a gap through which they attach to the underlying collagen coating. Notably\, we found that clusters expressing more LGR5 have an advantage while attaching to the endothelium as indicated by higher attachment rate and shorter time to form a gap. \n\n\n\nBased on these findings relating distinct mechanical phenotypes to LGR5 expression\, we speculate that mechanical adaptability coupled with cancer plasticity may be an indispensable mechanism for cancer progression.
URL:https://ibecbarcelona.eu/event/phd-discussions-sefora-conti/
LOCATION:IBEC\, floor 11\, tower i
CATEGORIES:PhD Discussions Session
END:VEVENT
BEGIN:VEVENT
DTSTART;TZID=Europe/Madrid:20220429T100000
DTEND;TZID=Europe/Madrid:20220429T120000
DTSTAMP:20260505T151727
CREATED:20220422T065109Z
LAST-MODIFIED:20220422T065109Z
UID:96589-1651226400-1651233600@ibecbarcelona.eu
SUMMARY:PhD Discussions: Sefora Conti
DESCRIPTION:Mechanical phenotyping of colorectal cancer patient derived organoids based on LGR5 expression\nSefora Conti\, Integrative cell and tissue dynamics group \nColorectal cancer (CRC) tumors are composed by heterogeneous cell populations comprising differentiated cells and a small pool of cancer stem cells (CSCs). The link between cancer cell differentiation states and their metastatic potential has been the focus of extensive investigation\, with some studies pointing to microenvironmentally defined plasticity as a mechanism indispensable for metastasis formation. Another aspect that might be determinant in tumor cells ability to successfully disseminate\, intravasate\, survive in the blood stream\, extravasate\, colonize distant organs and form secondary tumors is their mechanical phenotype. \nAdopting a bottom-up approach\, we performed a broad biophysical characterization of CRC patient derived organoids (PDOs)\, engineered to fluorescently label cells expressing LGR5\, a well-established marker for CSCs. We show that CRC cells differentiation states are associated with distinct biomechanical phenotypes\, with potential repercussions on their metastatic ability. \nAt the single cell level\, LGR5+ cells display a more elongated and polarized shape while the LGR5- cells exhibit higher roundness and a smaller asymmetry in the stress field. LGR5+ are stiffer compared to their differentiated counterparts and more prone to adopt a fast amoeboid-like migration under confinement.  At the molecular level\, cancer stemness is related to differential expression of the ERM protein family\, responsible of tethering the cell membrane to the underlying actin cortex. \nThese distinct mechanical phenotypes translate to different migratory and morphological phenotypes at a cluster level. Clusters expressing high levels of LGR5 showed a more spread and flattened shape compared to more differentiated clusters. Moreover\, LGR5 expression in clusters is negatively correlated with their migration speed and their polarization state. Hence\, clusters containing more differentiated cells migrate faster\, display higher roundness and higher polarization state. \nAt higher complexity levels\, such as interactions with endothelial cells\, LGR5 expression in CRC clusters affects their ability to adhere to an endothelial monolayer and form a gap through which they attach to the underlying collagen coating. Notably\, we found that clusters expressing more LGR5 have an advantage while attaching to the endothelium as indicated by higher attachment rate and shorter time to form a gap. \nBased on these findings relating distinct mechanical phenotypes to LGR5 expression\, we speculate that mechanical adaptability coupled with cancer plasticity may be an indispensable mechanism for cancer progression.
URL:https://ibecbarcelona.eu/event/phd-discussions-sefora-conti-2/
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:20220527T100000
DTEND;TZID=Europe/Madrid:20220527T120000
DTSTAMP:20260505T151727
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:20260505T151727
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
END:VCALENDAR