Institute for Bioengineering of Catalonia

IBEC Seminar: Johanna Ivaska
2018-02-28 10:00 - 11:00 (Europe/Madrid) | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Mechanosensitive regulation of cancer and pluripotency
Johanna Ivaska, Turku Centre for Biotechnology, University of Turku, Finland
Tissue homeostasis is dependent on the spatially controlled localization of specific cell types and the correct composition of the extracellular stroma. Integrin mediated adhesions, in conjunction with the actin cytoskeleton, allow cells to sense the stiffness of the surrounding extra-cellular matrix (ECM). Conversely, cells exert acto-myosin and integrin dependent forces to remodel and organize the surrounding ECM. In cancer, stiffening of the tumor stroma is considered as an instrumental contributor to tumor progression. However, the mechanisms how stromal ECM regulates cancer progression is not fully understood. I will describe our recent findings on the interrelationship between cancer cell mediated ECM remodelling and ECM induced mechanochemical signals regulating transcription of growth promoting pathways in cancer cells. Reprogramming and survival of human pluripotent stem cells is heavily influenced by their adhesion to the underlying ECM. We have recently investigated the link between ECM-adhesion, the actin cytoskeleton and cell contractility in maintenance of pluripotency. I will describe our recent efforts to define the stem-cell adhesion structure in nanoscale and how it contributes to maintenance of pluripotency.

IBEC Seminar: Carlo A. Bortolotti
2018-03-20 16:00 - 17:00
Monitoring biorecognition with organic bioelectronic transistors
Carlo A. Bortolotti, Dipartimento di Scienze della Vita, Universita di Modena ed Regio Emilia, Italy
Electrolyte-gated OFETs (EGOFETs) and Organic Electrochemical transistors (OECTs) are emerging as an important class of chemo- and biosensors to meet the main requirements of healthcare diagnostics: portability, manufacturing with low cost, miniaturization, low-temperature processing. These devices can be operated either in accumulation (EGOFETs) or in depletion mode (OECTs). Devices that allow transduction of protein/protein interactions can be used not only for analytical purposes, but also for real time monitoring of surface adsorption and recognition events, and may therefore provide insights into both the kinetics and thermodynamics of biomolecular interactions. These devices provide a real-time, label-free response and the ultra-low sensitivity arising from the capacitive coupling between the electrolyte solution and the channel. We are currently investigating a wide range of biorecognition events, differing in terms of size of the surface bound biomolecule and of the chemical nature and lateral dimensions of the biological partner in solution, ranging from receptor/ligand interactions to antibody/antigene (protein) and antibody/virus couples. I will present a few examples of the EGOFET-based and OECT-based detection of detection of biorecognition events. Different surface functionalization strategies, aiming at reducing non-specific binding, increasing sensitivity and ensuring re-usability of the electrodes with immobilized sensing units will be described. I will also present our latest achievements in the development of a multigate lab-on-a-chip device, aiming at the multiplexed detection of different analytes in a biological fluid, also including an internal reference electrode.

IBEC Seminar: Aurélien Bancaud
2018-03-28 10:00 - 11:00
µLAS technology for DNA processing: setting up elementary functions (concentration, separation, purification, identification) and application in oncology and targeted sequencing
Aurélien Bancaud, LAAS-CNRS, Toulouse, France
We recently developed the µLAS technology for nucleic acids processing. Its operating principle relies on the monitoring of DNA transport in a viscoelastic liquid under the combined action of hydrodynamic and electrophoretic forces (1). DNA molecules are dragged toward the walls of microchannels by a transverse force proportional to their contour length. Because the hydrodynamic decreases near the wall, DNA molecules are sorted according to their molecular weight. Furthermore, by tailoring the geometry of a channel with a constriction, we can tune the amplitude of transverse forces and stop molecules to design a concentrator that achieves enrichment rates of 100 to 1000 fold per minute.
We will derive a quantitative model of DNA transport in µLAS that relies on 1 fitting parameter and perform rational optimizations of the technology. We will then exploit µLAS for sizing cell-free circulating DNA (cfDNA) in the blood (2), and demonstrate that cfDNA profiling is a promissing biomarker for the follow-up of cancer patients. Finally, we will present the principle of a DNA size-selective valve for the purification and sequencing of target genomic regions by combining µLAS with Cas9 endonuclease.
(1) Ranchon et al., Lab Chip (2016)
(2) Andriamanampisoa et al., Anal Chem (2018)

IBEC Seminar: Fernando López-Gallego
2018-04-04 12:00 - 13:00
Immobilization of multi-enzyme systems; an avenue to fabricate self-sufficient heterogeneous biocatalysts
Fernando López-Gallego, Heterogeneous Biocatalysis Lab, University of Zaragoza (iQSCH-CSIC) / ARAID, Science Foundation of Aragón
In the last decade, the chemists have been delighted by the catalytic orchestration found in vivo, and have isolated multi-enzyme system to work ex-vivo in both natural and non-natural tandem reactions creating a new concept: systems biocatalysis. These systems are the pioneers of the cell-free synthetic biology; an emerging discipline that seeks the simplest biology to make the most complex chemistry. We have paid our attention to the heterogenization of multi-enzyme system to catalyze tandem reactions. Co-immobilization of multi-enzyme systems improve: 1) the kinetics of the chemical cascades due to the spatial localization of the different biocatalytic modules that avoids intermediate accumulation and increases cofactor recycling efficiency, 2) the stability of the biocatalysts due to both structural rigidification and in situ elimination of toxic by-products, 3) the biocatalyst recycle and 4) the biocatalyst adaptation to continuous processes. Nevertheless, the co-immobilization of several enzymes to carry out synthetic cascades is challenging because there is no a universal immobilization chemistry that optimally attaches all the enzymes to the same surface. We have recently developed different immobilized multi-enzyme systems formed by a 3-enzyme cascade for oxidizing phenol derivatives with in situ H2O2 supply, a 3-enzyme cascade for synthesizing 1,3-dihydroxyacetone with both in situ cofactor recycling and H2O2 elimination, a 4-enzyme cascade for quantitatively synthesizing pro-chiral ketones starting from racemic esters and a 2-enzyme cascades to synthesize optically pure secondary alcohols integrating the cofactor recycling in the solid-phase. The optimal design of the immobilization protocols enables co-immobilizing several enzymes and cofactors on the porous carrier to optimize their spatial localization across the carrier microstructure and preserve both global activity and stability of the multi-enzyme systems.

IBEC Seminar: Joan Seoane
2018-04-13 10:00 - 11:00
Intratumor heterogeneity in brain cancer
Joan Seoane, Group Leader / Director of Translational Research at Vall d’Hebron Institute of Oncology (VHIO)
Joan Seoane is a Group Leader and Director of the Translational Research program at the Vall d’Hebron Institute of Oncology (VHIO) within the Vall d’Hebron University Hospital since 2011.
In 1998, Joan obtained his PhD in Biochemistry and Molecular Biology from the University of Barcelona. Previously, in 1993, he obtained his BSc degree in Chemistry. Joan joined the Memorial Sloan-Kettering Cancer Center (MSKCC) in New York as a post-doctoral fellow in 1998.
From 1998 to 2001, he worked as a Research Fellow and subsequently, from 2001 to 2003, as a Research Associate. He was appointed ICREA Research Professor in 2004 and joined VHIO.
In 2007, he became a member of the EMBO Young Investigator program and the recipient of a European Research Council (ERC) grant in 2008. Later, he obtained two ERC Proof of Concept grants (2011, 2013). In 2008, he became Board member of the European Association of Cancer Research (EACR) and Professor of the Autonomous University of Barcelona.
In 2012, founded Mosaic Biomedicals as a spin-off company from his lab and, in 2013, he was the recipient of the Dr. Josef Steiner Award. In 2016, he became Secretary General of the EACR.

IBEC Seminar: (David) Dagan Feng
2018-04-20 10:00 - 11:00
Biomedical Engineering and Technology Research at USYD and beyond
(David) Dagan Feng, PhD, FACS, FATSE, FHKIE, FIEEE, & FIET
Recent advances in engineering, information technology and imaging have revolutionized biotechnology, biomedical research and healthcare. This talk will initially focus on some of his core theories and enabling techniques research in molecular imaging for E-Healthcare and its impact to clinical practice, in particular in cancer and metabolic diseases. This talk will then give an overview of the Biomedical Engineering and Technology research at the University of Sydney and beyond, in particular several University new initiatives and the USYD-SJTU Joint Research Alliance.

IBEC Seminar: Francesco Ricci
2018-05-02 12:00 - 13:00
DNA-based nanodevices for diagnostic and drug-delivery applications
Francesco Ricci, Chemistry Department, University of Rome, Tor Vergata, Rome, Italy
DNA nanotechnology uses DNA (or nucleic acids) as a versatile material to rationally engineer tools and molecular devices that can find a multitude of different applications (e.g., in-vivo and in-vitro diagnostics, drug delivery, genetic circuits etc.).
During this presentation I will introduce the field of DNA nanotechnology and I will talk about some of the most exciting examples of the last decade.
I will show how to exploit the “designability” of DNA to fabricate nature-inspired DNA-based nanoswitches and nanodevices that are specifically designed to undergo a conformational change (switch) upon binding to a specific input (i.e. target). This input-triggered conformational change can be used for diagnostic, drug-delivery or synthetic-biology applications.
I will demonstrate how to characterize and recreate in-vitro several mechanisms to control the response of DNA-based nanodevices (1-2) and how to regulate their activity with different chemical and environmental stimuli including pH (3-8), antibodies (2-3), enzymes (9), small molecules (10) and electronic inputs (11).
References
[1] Porchetta. A., et al., J. Am. Chem. Soc., 2013, 135, 13238.
[2] Ranallo, S. et al., Angew. Chem., 2015, 54, 13214.
[3] Ranallo, S. et al., Nat. Commun., 2017, 8, 15150.
[4] Idili, A. et al., Nano Lett., 2015, 15, 5539.
[5] Porchetta, A, et al. Nano Lett., 2015, 15, 4467.
[6] Amodio, A. et al., J. Am. Chem. Soc., 2014, 136, 16469.
[7] Idili, A. et al., J. Am. Chem. Soc., 2014, 136, 5836.
[8] Mariottini, D. et al., Nano Lett., 2017, 17, 3225.
[9] Amodio, A. et al., J. Am. Chem. Soc., 2016, , 138, 12735.
[10] Del Grosso, E. et al., Nano Lett., 2015, 15, 8407.
[11] Ranallo, S. et al., Chem. Sc., 2016, 7, 66-71.

IBEC Seminar: Mar Alvarez
2018-06-08 10:00 - 11:00
Organ-on-chip monitoring
Mar Alvarez, Ramon y Cajal researcher, Biomedical Applications Group, IMB-CNM
Organ-on-chip (OOC) is the term used to define a microfluidic 3D culture model that contains continuously perfused chambers inhabited by living cells. The development of the OOC technology has been possible thanks to the advancement in micro- and nanotechnologies. The engineered cellular microenvironments reproduce more accurately the in vivo structure and physiological conditions, and allow simulating the activities, mechanics and physiological response of tissues and organs. OOC are considered as very promising tools for investigating many aspects of human physiology and pathophysiology as well as drug testing platforms with future progressions to be used for precision medicine. As the complexity of OOC systems increases, the necessity to integrate relevant assessment methods to provide information about cell physiology, secreted metabolites as well as pharmacodynamics drug responses also increases.
In this talk, I will focus on the different engineering approaches that we have used to develop physical and chemical sensors that can be integrated into OOC. I will describe our recent works on biological barrier models, including blood-retinal barrier, renal tubule and liver sinusoid. In particular, I will talk about compartmentalization strategies and integration of transepithelial electrical resistance electrodes into these models, fabricated by standard photolithographic processes, for the on-line quantification of ion permeability and continuous evaluation of the barrier functioning. I will as well describe the integration of inkjet-printed electrodes into the culture porous membrane for the monitorization in real-time of the dissolved oxygen levels.

IBEC Seminar: Vivek Shenoy
2018-06-15 10:00 - 11:00
Cell-Matrix Interactions in Fibrosis and Cancer: Multiscale mechano-chemical models
Vivek Shenoy, University of Pennsylvania
Much of our understanding of the biological mechanisms that underlie cellular functions, such as migration, differentiation and force sensing has been garnered from studying cells cultured on two-dimensional (2D) substrates. In the recent years there has been intense interest and effort to understand cell mechanics in three-dimensional (3D) cultures, which more closely resemble the in vivo microenvironment. However, a major challenge unique to 3D settings is the dynamic feedback between cells and their surroundings. In many 3D matrices, cells remodel and reorient local extracellular microenvironment, which in turn alters the active mechanics and in many cases, the cell phenotype. Most models for matrices to date do not account for such positive feedback. Such models, validated by experiments, can provide a quantitative framework to study how injury related factors (in pathological conditions such as fibrosis and cancer metastasis) alter extracellular matrix (ECM) mechanics. They can also be used to analyze tissue morphology in complex 3D environments such as during morphogenesis and organogenesis, and guide such processes in engineered 3D tissues. In this talk, I will present discrete network simulations to study how cells remodel matrices and how this remodeling can lead to force transmission over large distances in cells. I will also discuss an active tissue model to quantitatively study the influence of mechanical constraints and matrix stiffness on contractility and stability of micropatterned tissues.

IBEC Seminar: Cristina Canal
2018-07-06 10:00 - 11:00
Cold atmospheric plasma: a novel potential therapy for cancer treatment
Cristina Canal, Biomaterials, Biomechanics and Tissue Engineering (BBT), UPC
Over the last few years, significant attention has been paid to biomedical applications of Atmospheric Pressure Plasmas (APP). Plasma chemistry leads to the generation of an abundance of reactive species which are suspected to play a key role in selective cancer cell death [1] without damaging surrounding healthy tissues [2]. The anti-cancer properties of the APP have been described in many cancer cell lines, such as breast, skin, lung, pancreas, cervix and brain cancers and only more recently in bone cancer cells [3-4]. Although the cell death mechanisms are not yet precisely known, this selectivity towards cancer cells is associated in literature to the reactive oxygen and nitrogen species (RONS) generated by the plasma treatment, among other potential actors. In this talk we will introduce different plasma oncology concepts and will discuss some of our first results related to plasma treatment and plasma activated medium treatment of osteosarcoma and the selectivity of the treatment.

IBEC Seminar: Ina Meiser, Cryobiotechnology group manager, IBMT
2018-07-16 12:00 - 13:00
Application oriented cryopreservation and banking of stem cells and stem cell derivates
Dr. Ina Meiser, Cryobiotechnology group manager, Fraunhofer Institute for Biomedical Engineering (IBMT)
Cryopreservation is still the only possibility to store viable cells for long periods. In general, conventional slow freezing methods are efficient enough to preserve single cells in suspension for subsequent expansion (e.g. human induced pluripotent stem cells, hiPSCs). Here, several aspects have to be taken into account for safe long-term storage regarding infrastructure and handling according to planned purpose. However, in case of preservation of adherent cells or multicellular systems that are increasingly relevant for biomedical research and application (e.g. hiPSC-derived neuronal cells), slow freezing shows major limitations. (1) Usually the adherent cells have to be enzymatically or mechanically dissociated to single cells or small aggregates prior to freezing, (2) crystallization-induced damaging mechanisms additionally disrupt cadherin- and integrin-mediated cellular contacts, and especially for hiPSC, (3) the recovered viable cell numbers is dramatically reduced compared to the control. Besides application of sophisticated scaffolds in slow freezing approaches, the method of ice-free cryopreservation (vitrification) provides the possibility to overcome these limitations, but requires skilled handling especially regarding sterile procedures, implies small sample sizes and therefore is considered as unsuitable for routine handling or bulk storage. To launch vitrification for large cell numbers and thus enabling ready-to-use cryopreserved adherent cell systems, a sophisticated multi-usage cell culture disposable covering comprehensive cell-based workflows from cultivation/differentiation to sterile vitrification will be introduced.

IBEC Seminar: Hiroshi Ishida, Tokyo University of Agriculture and Technology
2018-07-20 10:00 - 11:00
Active Flow Generation for Mobile Robot Olfaction and Olfactory Assisting Devices
Prof. Hiroshi Ishida, Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology
Mobile robots can be used as moving platforms for various gas sensing tasks in the field, e.g., gas source localization and gas distribution mapping. In the presentation, it will be shown that actively generated airflow can be used to facilitate such robotic gas sensing tasks. Reception of chemical substances at the chemical sensors on a robot can be significantly enhanced by generating a carefully designed airflow field around the sensors. Olfactory assist systems that allow the user to sense smells with amplified sensitivities are also reported.

IBEC Seminar: Dr. Kevin Chalut, Cambridge Stem Cell Institute
2018-07-23 11:00 - 12:00
Mechanical signaling and cell fate
Dr. Kevin Chalut, Cambridge Stem Cell Institute
The role of mechanical signaling in cell fate choice has been largely overlooked; however, it plays a significant role in tuning cellular response to signals. My lab is investigating the interplay between biochemical signaling and mechanical signaling in cell fate decisions. I will show first in the mouse embryo that biochemical signaling modulates cytoskeletal contractility to influence spatial positioning and solidify cell fate choice. I will then show that mechanics tunes the response of the cell to biochemical signaling to steer fate choice. This hypothetical feedback loop between mechanics and biochemical signaling likely has significant impact on cellular plasticity both in development and stem cells. I will also present an example demonstrating the functional impact of mechanics on stem cell function. In this example, we have shown that we can reverse the loss of plasticity associated with ageing by controlling the mechanical microenvironment. Ultimately, I will advance the hypothesis that mechanical sensing acts as a switch to modulate growth factor signaling to modulate cell fate choice.

IBEC seminar: Yunuen Avalos
2018-09-21 10:00 - 11:00
GUVs as biomimetic systems to study pathogenic-related mechanisms of human parasites
Dr. Yunuen Avalos, BEST Cofund postdoc, Nanomalaria group, IBEC
Membrane models such as Giant Unilamellar Vesicles (GUVs) are a powerful tool for studying reactions occurring in living cells. The main advantage of using these biomimetic systems is the vast possibility of controlling the conditions such as membrane composition, surrounding media and temperature; therefore, minimizing the complexity occurring in normal circumstances and allowing us to understand the mechanism of the membrane-related reactions.
In this talk I will focus on the use of GUVs for the reconstitution of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery whose transitory nature on living membranes makes it difficult to study via in vivo systems. The ESCRT machinery is involved in important membrane-remodeling processes in eukaryotes such as cytokinesis, virus budding, plasma membrane repair, neuron pruning, etc. In all of these reactions, the ESCRT machinery orchestrates the fusion of buds that forms away from the cytosol, contrary to the process regulated by clathrin-coated vesicles. In protozoan parasites such as Plasmodium facilparum and Entamoeba histolytica (causative agents of Malaria and Amebiasis, respectively), the ESCRT machinery controls processes involved in the pathogenic mechanisms, such as exosome generation for Plasmodium and endosome maturation in Entamoeba. By using GUVs as a model system, the action of the ESCRT machinery from these and other organisms has been successfully reconstituted. The GUVs system allowed us to unveil the assembly sequence and the function of the proteins at the membrane. Moreover, we have recreated the topology occurring in living cells by a femto-injection approach. The results derived from these experiments can be used to find new therapeutic targets for the eradication of these parasitic diseases.

IBEC Seminar: Prof. Rui L. Reis
2018-10-08 12:00 - 13:00
New Approaches, combining natural materials and stem cells, for the Engineering of Different Types of Tissues
Prof. Rui L. Reis, University of Minho
The selection of a proper material to be used as a scaffold or as a hydrogel to support, hold or encapsulate cells is both a critical and a difficult choice that will determine the success of failure of any tissue engineering and regenerative medicine (TERM) strategy.
We believe that the use of natural origin polymers, including a wide range of marine origin materials, is the best option for many different approaches that allow for the regeneration of different tissues. In addition to the selection of appropriate material systems it is of utmost importance the development of processing methodologies that allow for the production of adequate scaffolds/matrices, in many cases incorporating bioactive/differentiation agents in their structures.
Furthermore an adequate cell source should be selected. In many cases efficient cell isolation, expansion and differentiation, and in many cases the selection of a specific sub-population, methodologies should be developed and optimized. We have been using different human cell sources namely: mesenchymal stem cells from bone marrow, mesenchymal stem cells from human adipose tissue, human cells from amniotic fluids and membranes and cells obtained from human umbilical cords.
The development of dynamic ways to culture the cells and of distinct ways to stimulate their differentiation in 3D environments, as well as the use of nano-based systems to induce their differentiation and internalization into cells, is also a key part of some of the strategies that are being developed in our research group.
The potential of each combination materials/cells, to be used to develop novel useful regeneration therapies will be discussed. The use of different cells and their interactions with different natural origin degradable scaffolds and smart hydrogels will be described. Several examples of TERM strategies to regenerate different types of tissues will be presented. This will include the use of original high-throughput methodologies to look at materials/cell interactions.
