Institute for Bioengineering of Catalonia

IBEC Seminar: Matteo Palma
2015-06-19 10:00 - 11:00 (Europe/Madrid)
Bio-inspired self-assembly for single-molecule investigations

Matteo Palma, Queen Mary University of London
One of the ultimate goals in nanotechnology is the ability to produce efficient devices based on individual molecules and nanostructures. Despite the many potential benefits envisioned for single-molecule technology (in electronics and biotechnology) the strategies employed to date suffer from various limitations. Principal among these limitations is the poor control over the molecular assembly of nanostructures and individual molecules with respect to one another, as well as their position on devices with respect to other material components.
I will first discuss techniques based on the combined use of lithographic nanopatterning and bio-molecular self-assembly to control the immobilization of biomolecules in arrayed nanodomains. I will show how this allows us to produce highly ordered, self-assembled arrangements of nano-objects, ranging from proteins to DNA nanostructures, and bio-inorganic assemblies, for a variety of (nanoscale) investigations.
I will show how by specific design of the biomolecular nanoarrays, it is possible to simultaneously monitor hundreds of protein/DNA binding events at the single-molecule level. Moreover I will discuss the use of our nanopatterned biomimetic surfaces to probe the importance of transmembrane proteins (integrins) clustering and geometric arrangement of binding sites, in the formation of cell focal adhesions
I will then highlight the broader utility of such nanopatterned surfaces for the self-organization (on surfaces) of bio-inorganic assemblies as well as DNA nanostructures and carbon nanotubes. In particular, I will discuss how the combination of high resolution patterning with end-functional chemistry enables the assembly of 1D functional nanostructures in an orderly fashion.
Finally, building on our novel bottom-up assembly strategy for the formation of (chemically and geometrically) versatile carbon nanotube (CNTs) junctions, I will present a universal approach for the generation of multifunctional nanomaterials that employ molecular building blocks assembled between DNA wrapped CNT electrodes. We will demonstrate single-molecule control in the formation of nanohybrids via the in-solution assembly of classes of molecular materials (organic, and inorganic which display promising attributes) to DNA wrapped CNTs. We believe this may be a viable avenue towards the integration of these materials in complex and functional nano-architectures.
Our findings are of general interest for the controlled assembly of a broad range of functional molecules and nanostructures, towards the fabrication of solution-processable nanoscale devices. Moreover, we believe that the knowledge developed makes a significant contribution towards the facile fabrication of nanohybrid materials for single-molecule investigations. Future technologies will require devices of this type in a variety of key areas, including biodiagnostics, ultra-high speed computation, bioelectronics, and for renewable energy applications.

IBEC Seminar: Javier G. Fernández
2015-06-16 16:00 - 17:00
Bioinspired materials

Javier G. Fernández, Assistant Professor and Founder Academic Member · Singapore University of Technology and Design
Nature is abundant with materials that possess extraordinary mechanical characteristics. New techniques in biochemistry and advances in microelectronic engineering are boosting our knowledge of biological materials, and providing tools to fabricate at the scale at which these materials are made in nature. This investigation of the structural organization of these materials leads to understanding of the principles of natural materials design that are beginning to be harnessed to fabricate biologically-inspired composites for materials engineering with tunable properties that mimic living materials, which might provide useful for environmental challenges, as well as medical applications.

IBEC Seminar: Alexandra P. Marques
2015-06-12 10:00 - 11:00
Driving skin wound healing: stem cells and extracellular matrix role

Alexandra P. Marques, 3B’s Research Group, University of Minho, Portugal
Wound care products have evolved into skin tissue engineered substitutes, which despite the longest history of application and the highest record of marketing, proved to represent replacement strategies instead of promoting tissue regeneration.
Current research indicates that the interactions between resident progenitor cells and their niche dictate the triggering of skin regeneration pathway. In alignment, mesenchymal stem cells (MSCs)-based therapies, have been proposed to enhance cutaneous wound healing. The rationale lies on transplanted cells ability to interact/respond to the wound microenvironment, which is advantageous when compared to the exogenous administration of healing factors. However, the involved mechanisms are still elusive and poor outcomes were achieved in terms of attainment of functional skin tissue due to low cell survival rates, and poor engraftment or cell fusion upon transplantation. Extracellular matrix (ECM)-mimicking is currently seen as the “Holy Grail” of Tissue Engineering in the sense that by recreating natural tissues microenvironments researchers will be able to increase the residence time and consequently the action of the transplanted cells and thus uncover “therapeutic niches”.
Under this context we have been exploring two perspectives; one takes advantage of the tunable ECM-like properties along with the 3D support that hydrogels can provide, and the second benefits from an intact native ECM offered by cell sheet engineering technology. Hydrogels features such as high hygroscopic nature, tunable elasticity and facilitated mass transportation, render such materials attractive for the development of skin ECM-analogues. Although succeeding in improved cell engraftment, hydrogels fail to provide biological instructive cues as well as cell adhesion sites, only overcome by cell adhesive peptides bonding to polymers backbone. We developed a new method of processing gellan gum-based materials, having as start material gellan gum-based hydrogels, to obtain structures that exhibit features of both sponges and hydrogels depicting intrinsic cell-adhesive properties. By creating constructs comprising adipose tissue cells and artificial and natural ECM we were able to demonstrated that skin healing is dependent on tissue engineered constructs self cell-cell and cell-ECM interactions, as well as on constructs cell-cell interactions and paracrine signaling with resident cells. In particular, our results suggest that cell-ECM and cell-cell interactions have a dramatic effect over re-epithelialisation. In opposition, neo-vascularisation did not seem to be dependent on the nature of the cell-ECM interactions, but was significantly improved with the incorporation of microvascular endothelial cells.
Ultimately the generation of knowledge on how to direct skin regeneration lead the creation of “off-the-shelf” 3D stem cell-based engineered products inspired by the role of wound healing microenvironments.

IBEC Seminar: Thomas Graf
2015-05-22 10:00 - 11:00
Mechanisms of transcription factor induced transdifferentiation and reprogramming to pluripotency

Thomas Graf, Gene Regulation, Stem Cells and Differentiation Programme, CRG / Pompeu Fabra University
Work by many laboratories has shown that even fully differentiated cells are remarkably plastic and can be reprogrammed into alternative fates. This discovery has revolutionized our understanding of how cell decide what to become and has major implications for the modeling and therapy of diseases that affect the production of differentiated cells.
Our earlier work has shown that the myeloid transcription factor C/EBPa induces B cells to transdifferentiate into macrophages at high efficiencies. We have now found that the process forces the intersection of two enhancer pathways that become activated during normal hematopoietic differentiation.
Recently we reported that the transient expression of C/EBPa in B cells, followed by expression of the pluripotency factors Oct4, Sox2, Klf4 and c-Myc (OSKM), poises the cells for very rapid and highly efficient reprogramming into induced pluripotent stem cells. Our findings have removed a major obstacle in studying cell reprogramming and permitted us to investigate how C/EBPa leads to the almost immediate accessibility of pluripotency genes to binding by Oct4. Our new data provide unprecedented insights into the earliest events leading to activation of the pluripotency gene regulatory network, resulting in somatic cell reprogramming.

IBEC Seminar: J. Miguel Rubi
2015-05-08 10:00 - 11:00
Somatic exocytosis of serotonin mediated by molecular motors

J. Miguel Rubi, Departament de Fisica Fonamental, Universitat de Barcelona
We quantified somatic exocytosis of serotonin in Retzius neurons and explored the possible contribution of molecular motors and the cytoskeleton on the mobilization of vesicles induced by stimulation with trains of electrical impulses. Secretion was quantified from the increase of fluorescence of FM1-43 in response to sequences of 20 mV trains of 10 impulses at 2 min intervals, produced by intracellular current injection. Somatic secretion was also evoked by a pulse of 10 mM caffeine applied to the bathing solution. Stimulation of neurons produced a gradual increase in FM1-43 fluorescence for over the next five minutes. The kinetics and latencies of these increases varied from one neuron to another but usually maintaining a sigmoidal shape in one or two steps. Neurons stimulation in the presence of colchicine to uncouple microtubules, failed to evoke fluorescence increases, thus suggesting that vesicle mobilization depended on tubulin-based motor. The kinetics of the fluorescence increases of individual neurons was accounted for by using a model based on a diffusion equation in the presence of external forces, consistent with the contribution of molecular motors to the mobilization of the vesicle clusters towards the membrane in response to electrical activity. Our data show that somatic serotonin secretion in Retzius neurons depends on a motor-based cytoskeletal mobilization of vesicles induced by electrical activity.

IBEC Seminar: Núria Montserrat
2015-04-10 10:00 - 11:00
Dreaming of organ regeneration: new hopes for regenerative medicine

Núria Montserrat, Pluripotent stem cells and activation of endogenous tissue programs for organ regeneration group, IBEC
Dr. Montserrat became interested in organ regeneration and stem cells during her master in biological research and PhD training. She completed her PhD with Dr. Joaquim Gutiérrez and Isabel Navarro at the Faculty of Biology, University of Barcelona in 2006. During her master and PhD studies, she set-up in vitro platforms for the study of skeletal muscle stem cells during homeostasis and under different metabolic conditions. During her PhD studies she did several stages at other European laboratories: Manfred Reinecke’s laboratory at the University of Zurich and at Jean-Charles Gabillard’s laboratory in INRA SCRIBE, France. In 2006,Dr. Montserrat got her European PhD degree at the University of Barcelona.
In 2006 she got a Postdoctoral fellowship from the Fundaçao para a Ciência e Tecnología (Portugal) and in 2007 she was hired as a post-doctoral researcher at at the Hospital of Santa Creu i Sant Pau in Barcelona. Early in 2008 she joined the Center of Regenerative Medicine of Barcelona (CMRB) with the objective to study the molecular mechanisms driving tissue regeneration, somatic reprogramming and disease modeling.
The research line of Dr.Montserrat has been awarded with an ERC Starting Grant within the call of 2014. Recently, Dr. Montserrat has joined IBEC as Junior Group leader. Her aim is to develop strategies for tissue and organ engineering making use of pluripotent stem cells from patients and the reactivation of tissue endogenous programs.

IBEC Seminar: Romain Quidant
2015-03-20 10:00 - 11:00
Biomedical applications of nanoplasmonics

Romain Quidant, ICREA professor at Institut de Ciències Fotòniques (ICFO)
Gold nanostructures, supporting localized surface plasmon resonances, can be designed to act upon illumination as efficient point-like sources of either light or heat, opening plenty of new science and applications in biology and medicine. In this talk we discuss how both their optical and photothermal properties can be exploited to develop alternative, minimally invasive strategies for the detection and therapy of cancer.
The first part of this presentation focuses on the use of the intense and confined optical fields bound to gold nanostructures for biosensing and optical trapping. In the frame of sensing, we show that gold nanostructures lithographically prepared on glass can be engineered as compact and highly sensitive sensors to detect low concentrations of cancer markers in serum. As for optical trapping, we demonstrate that plasmonic fields enable creating on-a-chip nano-optical tweezers able to trap a large number of micro- and nano- specimens with a single laser beam of low laser intensity.
In the second part we talk about the use of gold nanoparticles as remotely controlled point-like sources of heat for photothermal cancer therapy. We first discuss, both theoretically and experimentally, the physics of heat generation at the nanoscale along with the effect of the particle shape and the illumination. We then present the use of conjugated gold nanoparticles for specific cancer cell hyperthermia.

IBEC Seminar: Gilles Subra
2015-02-27 12:00 - 13:00
Hybrid inorganic–biorganic peptide materials and polymers: a bottom-up approach

Gilles Subra, Institut des Biomolécules Max Mousseron (IBBMM), Montpellier
The preparation of hybrid materials containing peptides relies most of the time on physical entrapment of the bioorganic moiety or on a ‘post-grafting’ procedure. In the later case, introduction of the peptide requires surface modification and ligation chemistry performed after the synthesis of the material. In contrast, we designed a new family of bioorganic-inorganic hybrid materials relying on the synthesis of hybrid peptide-trialkoxsilyl building blocks that can be engaged directly in a sol gel process requiring no extra reagents.
This bottom-up approach permits the introduction of any type of peptide in the material, providing different functionalities, structural features, biological and physicochemical properties. The hybrid peptide block can be either grafted or introduced by direct synthesis. Several applications will be presented including the synthesis of silica multifunctional nanoparticles for imaging, peptide-catalytic mesopous materials, anti fouling glass surfaces and hydrogels. At last, the self-assembling properties of the peptide unit can be exploited to yield a range of bio-inspired nanostructured materials.
In an effort to develop polymerization systems suitable for peptide sequences, we also describe a new class of silicone-peptides biopolymers. We used well defined chlorosilyl hybrid peptides as mononeric units, synthesized in solution or on dedicated solid support to yield linear or comb-like peptide polymers.

IBEC Seminar: Pia Cosma
2015-02-13 10:00 - 11:00
Studying Wnt signaling activity in cell reprogramming and tissue regeneration

Pia Cosma, Center for Genomic Regulation (CRG) / ICREA
In our group, we are investigating the mechanisms controlling the reprogramming of somatic cells, and our final goal is to determine if this reprogramming contributes to tissue regeneration in higher vertebrates.
Differentiation from zygotes has been considered as a unidirectional route in all cells of the body. Recently, however, it has become clear that the reverse path is also possible: the reprogramming of somatic nuclei, i.e. the de-differentiation of somatic cells into pluripotent stem-like cells. To date, reprogramming has been induced in vitro by transferring somatic nuclei into enucleated oocytes, by fusing embryonic stem cells (ESCs) with somatic cells, and by transferring specific factors into different types of somatic cell.
Whether reprogramming can occur in vivo in higher vertebrates and what the molecular mechanisms and genes driving reprogramming are remain to be defined. We have recently shown that activation of the Wnt/β-catenin signalling pathway enhances reprogramming of somatic cells after their fusion with ESCs. Remarkably, the activation of this signalling pathway also controls regeneration in response to damage in lower and higher vertebrates; furthermore, cell fusion is one possible mechanism of regeneration in vertebrates. Our main goal is to determine whether in mice activation of Wnt/β-catenin signalling controls tissue regeneration by enhancing cell-fusion-mediated reprogramming.

IBEC Seminar: Daniel Oliver
2015-02-12 00:00 - 13:00
Crowdfunding for scientific and health projects

Daniel Oliver, Asociación Española de Crowdfunding
Mr. Oliver, president of Spain CrowdFund, will share his expertise fundraising for spinoff biotech companies. He will unveil the tricks that lead Iproteos to its success financing more than 100k€ through crowdfunding. Finally, he will present Capital Cell as the first co-investment platform specialized in scientific and health projects.

IBEC Seminar: Ralph G. Andrzejak
2015-02-03 10:00 - 11:00
Application of nonlinear signal analysis to electroencephalographic recordings from epilepsy patients

Tenure Associate Professor · Department of Information and Communication Technologies · Universitat Pompeu Fabra
Nonlinear time series analysis allows characterizing dynamical systems in which nonlinearity gives rise to a complex, seemingly irregular temporal evolution. Importantly, these nonlinear techniques can extract information from real-world experimental signals that cannot be resolved by classical linear techniques, such as spectral analysis. Nonlinear time series analysis can, for example, help to discriminate nonlinear deterministic and linear stochastic dynamics or to characterize directional interactions between dynamics. In application to signals measured from the brain, this analysis can contribute to the understanding of brain functions and dysfunctions. It can thereby advance cognitive neuroscience and neurology.
In this seminar, I will at first illustrate some fundamental concepts of nonlinear time series analysis. Subsequently, we will review some basic facts about the disease epilepsy, epilepsy surgery and intracranial electroencephalographic recordings (EEG) from epilepsy patients. I will then show an application of nonlinear time series analysis to EEG recordings from the seizure-free interval of epilepsy patients undergoing pre-surgical diagnostics. Results of this application allowed us to localize the seizure generating brain area without the necessity of observing actual seizure activity – a finding of clear clinical relevance.

IBEC Seminar: David Caballero
2015-01-16 10:00 - 11:00
The cell ratchet: interplay between protrusion activity and adhesion determines cell motion

David Caballero, Nanobioengineering group, IBEC
Many physiological and pathological processes involve directed cell motion, either collective or as single cells. Typically, migrating cells are characterized by a polarized morphology with extending and retracting protrusions at the leading edge. However, cell motion is a much more complex phenomenon. Cells show heterogeneous morphologies and high protrusive dynamics. This prevents the quantitative prediction of cell motion and the identification of the cellular mechanism responsible of directionality. In this seminar, I discuss about the importance of protrusion fluctuations in the physicochemical mechanism of directed cell motion. I show how their spatiotemporal distribution and dynamics determines univocally the direction of cell motion on NIH3T3 fibroblasts deposited on micropatterned adhesive ratchets. Novel physical concepts describing short-term cell motility are introduced which allows the prediction of parameters characteristic of long-term motion of cells. The obtained results may have important implications for the study of biological phenomena where directed cell migration is involved, such as morphogenesis or cancer.
