IBEC Seminar: Wieteke de Boer
2016-04-26 16:00 - 17:00 UTC
Optical activation of neurons through low power two-photon IR excitation of gold nanoparticles
Wieteke de Boer, Departments of Biological Sciences and Neuroscience, Columbia University
Selective optical stimulation of specific classes of excitable cells is a major goal in neurobiology. Here we propose the approach of indirect photostimulation through gold nanoparticles (Au NPs), which are conjugated to the neuronal membrane. Au NPs are frequently used in biological research due to their versatile applicability: they have a broad optical tunability, large absorption cross sections, can be made chemically stable and biocompatible, and most importantly they are non-invasive and non-toxic even up to excessively large quantities. We show that these NPs can facilitate reliable optical stimulation of neurons through the plasmonic effect using IR two-photon (2P) excitation, with extremely low excitation powers. The NPs can be easily tethered to any targeted tissue and are known to be excreted without inducing any permanent damage. Using this approach, Au NPs are an attractive alternative to genetic modification techniques (such as channelrhodopsins) as it circumvents potential issues often seen in those methods, e.g. poor signal-to-noise ratio, photo-instability, photo-toxicity and expression efficiency.

IBEC Seminar: Marina Martínez
2016-05-12 11:30 - 12:30 UTC | Sala 1, Torre D, PCB, Baldiri Reixac 4-8, 08028 Barcelona
How to improve proposals & strategy within Horizon 2020
Marina Martínez, The Spanish Office for Science and Technology (SOST-CDT)
The aim of this seminar is to advice researchers, research managers and research support services on how to improve their success ratio on EU proposals application. Moreover, she will give an overview of all H2020 landscape, as well as all the stakeholders involved in order to choose the best strategy within EU positioning.
Limited places available. Register here.

IBEC Seminar: The new IBEC Bio-AFM system
2016-05-19 12:00 - 13:00 UTC
The new IBEC Bio-AFM system: system’s performance, applications and users’ guide
Gabriel Gomila, Group Leader, Nanoscale Bioelectrical Characterization, IBEC
In this talk I will introduce the new Bio-Atomic Force Microscopy infrastructure of IBEC. I will start describing the components of the infrastructure, its location at IBEC and its potential performance. Then I will present some examples of application of this system, and show the first results obtained with it. Finally, I will explain the special rules for its use by IBEC users.

IBEC Seminar: Xavier Fernández-Busquets
2016-05-20 10:00 - 11:00 UTC
A Short (Hi)story of Malaria
Xavier Fernández-Busquets, Nanomalaria Joint Unit (IBEC/Barcelona Institute for Global Health)
Reportedly, malaria has been the killer of about half of all people who have ever lived, among which such celebrities as king Tutankhamun, Alexander the Great, and Genghis Khan. To commemorate the 2015 Nobel Prize in Physiology or Medicine awarded to Professor Youyou Tu, we will overview the fascinating history of this murderer disease through the small stories of its sufferers from dinosaurs to humans. From the exorbitant egos of renowned physicians to the shameful experiments in concentration camps and prisons during WWII, or from the darkest depths of malariotherapy to the shining lights leading to the discovery of some of its remedies, malaria will keep us in awe of its amazing (hi)story.

IBEC seminar: Isaac Gállego
2016-05-26 10:00 - 11:00 UTC
DNA Nanotechnology: from its Applications to the Self-Assembly in Alternative Solvents
Isaac Gállego, Georgia Institute of Technology, USA
DNA nanotechnology is a relatively new field that utilizes the DNA’s programmability and self-assembly properties to build custom-designed shapes at the nanometer scale. A common implementation is the DNA origami method, in which a M13 single stranded genome (scaffold) is folded by hundreds of complementary base-paired oligonucleotides (staples). DNA nanostructures have been successfully utilized to create two-dimensional and three-dimensional devices with applications in lithography, photonics, electronics, and the fabrication of inorganic materials. Herein, I will present to you my work on DNA nanotechnology, which includes: i) the development of a biosensor to dsiplay the DNA repair activity hAGT—an enzyme target for the development of cancer therapeutics;1 ii) the transfer a pre-programmed nanosclae pattern of DNA onto gold surfaces, a challenging process useful for the fabrication of functional materials; and iii) the first study of self-assembly of DNA nanostructures in a non-aqueous, alternative solvent, a deep eutectic solvent composed of glycerol and choline chloride in a 4:1 molar ratio (glycholine).2 Glycholine and its hydrated mixtures facilitate DNA folding by alleviating kinetic traps that are often encountered during the folding of DNA structures in aqueous solvent.
1. Tintoré, M., Gállego, I., Manning, B., Eritja, R. & Fàbrega, C. DNA Origami as a DNA Repair Nanosensor at the Single‐Molecule Level. Angew. Chem. Int. Ed. Engl. 52, 7747–7750
2. Gállego, I., Grover, M. A. & Hud, N. V. Folding and Imaging of DNA Nanostructures in Anhydrous and Hydrated Deep-Eutectic Solvents. Angew. Chem. Int. Ed. Engl. 54, 6765–6769 (2015).

IBEC Seminar: Prof. Shulamit Levenberg
2016-07-12 10:00 - 23:00 UTC
Engineering Vascularized Tissue Constructs
Prof. Shulamit Levenberg, Faculty of Biomedical Engineering, Technion, Haifa, Israel
Vascularization continues to represent a major challenge in the successful implementation of regenerative strategies. Cell organization into 3D tissue vascularized structures involves cell-matrix and cell-cell interactions, some of which occur between the different tissue cell types. During this process, cells further differentiate and assemble into structures resembling the final tissue architecture. We have established that vessel network assembly yielding vascularized 3D tissue structures can be induced in-vitro by means of coculturing endothelial cells, fibroblasts and tissue-specific cells. We have also shown that in vitro pre-vascularization of engineered tissues can promote tissue survival and further vascularization upon implantation, via anastomosis of the engineered vessels with host vasculature, forming functional blood vessels in vivo. Vascularization of engineered tissues can be enhanced through coordinated application of improved biomaterial systems with relevant cell types. Moreover, we have shown that vessel network maturity and morphology can be highly regulated by both matrix composition and by external mechanical stimulations. Our recent studies have focused on investigation of the degree of the in vitro prevascularization required to achieve best postimplantation vascularization of tissue constructs, as well as on understanding the mechanisms underlying host-implant vessel integration and anastomosis. New co-culture approaches for inducing pre-defined vessel structures in vitro will also be discussed, as will novel studies on vascularized muscle flaps engineered to reconstruct large soft tissue defects.

IBEC Seminar: Publishing in the Nature journals
2016-10-10 15:00 - 16:00 (Europe/Madrid) | Sala Félix Serratossa, Parc Científic de Barcelona, Barcelona, Spain
IBEC Seminar: Publishing in the Nature journals
Dr. Alexia-Ileana Zaromytidou (Chief Editor, Nature Cell Biology)
Alexia-Ileana Zaromytidou, Chief Editor of Nature Cell Biology will provide an editor’s perspective on the editorial and publishing process in the Nature journals.
She received her PhD from the London Research Institute of Cancer Research UK in London, UK (now the Francis Crick Institute) in January 2007. Her doctoral work with Richard Treisman centered on the molecular interactions between actin-regulated transcription factors and their coactivators in the context of MAPK and Rho signaling responses. She pursued her postdoctoral research in the lab of Joan Massagué at Memorial Sloan-Kettering Cancer Center in New York, where she studied how different phosphorylation inputs affect TGFβ/BMP pathway activity to achieve distinct biological outcomes. In September 2010 she joined the editorial team of Nature Cell Biology as the editor responsible for the areas of cancer biology, mechanobiology, cell adhesion, migration and the cytoskeleton, and became Chief editor of the journal in November 2015.

IBEC Seminar: Scaling up in Systems Biology: from a minimal cell to microbiomes
2016-10-13 10:00 - 11:00 (Europe/Madrid)
Scaling up in Systems Biology: from a minimal cell to microbiomes
Maria Lluch Senar, Design of Biological Systems grup, Centre for Genomic Regulation (CRG)
Ultra-sequencing technologies have allowed the massive identification of human-associated microbiomes. Genome annotations of microbiomes consider conserved ORFs or those encoding for proteins larger than 100aa. However, growing evidence highlight the existence of a hidden universe of small genes (smORFs) encoding for small peptides (SEPs; <100aa), many of them secreted, being involved in infection and quorum sensing. Also, in eukaryotes, small antimicrobial peptides (AMPs) are secreted in response to infection. The interplay between these secreted SEPs is essential to control the different human microbiomes to ensure coexistence rather than weakening the host against opportunistic infections. Thus, determining the smORFome of bacterial-host ecosystems and studying its role in homeostasis are essential. In this seminar, I will explain how by using different system biology approaches we discovered this layer of small peptides in Mycoplasma pneumoniae and our future plans to study their role in human microbiomes focusing in female reproductive tract.

IBEC Seminar: Targeting fibroblast durotaxis as anti-fibrotic therapy
2016-10-13 15:00 - 16:00 (Europe/Madrid)
Targeting fibroblast durotaxis as anti-fibrotic therapy
Dr. David Lagares, Harvard Medical School
Dysregulated wound repair process in response to chronic tissue injury can lead to the development of tissue fibrosis in most organs. Fibrosis is characterized by accumulation of collagens and other matrix proteins that result in the distortion of tissue architecture, and ultimately organ failure, in variety of human diseases including idiopathic pulmonary fibrosis (IPF). Tissue stiffening, traditionally thought to simply be a consequence of lung fibrosis, has been recently shown to be a contributing factor to its pathogenesis by inducing fibroblasts differentiation into activated myofibroblasts, the principal effector cells responsible matrix deposition.
The cellular and molecular mechanisms through which increased tissue rigidity drives disease progression remain to be fully elucidated. Using atomic force microscopy (AFM) to mechanically characterize the “topography”, i.e. the spatial distribution, of alterations in matrix stiffness produced in mouse models of lung fibrosis, we consistently found that stiffness, rather than being uniformly elevated in lung fibrotic tissues from animals models, rises and falls in spatial gradients between “peaks” and “valleys.” We hypothesize that the stiffness “peaks” represent areas in which the fibrotic process was initiated, or “nucleated”. Once fibrosis is nucleated, the stiffness gradients leading to these fibrotic peaks are amplified by fibroblast “durotaxis,” – the directed migration of cells from regions of lower to higher stiffness, which occurs in the absence of chemoattractant gradients. Using hydrogels that recapitulate the stiffness gradients observed in animal fibrosis models, we demonstrated durotaxis of lung fibroblasts in time-lapse microscopy studies. In human studies with lung tissues from IPF patients, AFM revealed similar stiffness topography as we observed in mouse models, i.e. the presence of focal peaks surrounded by stiffness gradients. Of note, we have also found that primary lung fibroblasts from IPF patients exhibit greater durotactic responses to stiffness gradients than do control lung fibroblasts. In efforts to identify the molecular pathways involved in cell durotaxis, we have found that the increased durotaxis of IPF fibroblasts may be attributable, at least in part, to increased acetylation of their microtubules. Acetylation of α-tubulin is dependent on α-tubulin acetyltransferase (αTAT1) activity, which is upregulated in fibrotic fibroblasts compared with controls. siRNA-mediated αTAT1 downregulation in these fibrotic fibroblasts reduced their pro-durotactic phenotype without affecting fibroblast chemotaxis. In vivo, αTAT-1-deficient mice were protected from bleomycin-induced lung fibrosis, as assessed qualitatively by histology and quantitatively by hydroxyproline levels. Together, we identified a novel mechanism through which gradients of matrix stiffness produced in the injured lung drives the progression of lung fibrosis, by recruiting additional fibroblasts to sites of injury and incipient fibrosis through durotaxis. We consequently hypothesize that inhibition of fibroblast durotaxis has the potential to be an entirely new therapeutic strategy for IPF and other fibrotic diseases.

IBEC Seminar: Dr. Silvia Muro, Nanobiotechnology for drug delivery
2016-11-16 12:30 - 13:30 (Europe/Madrid)
Nanobio-technology for drug delivery: fundamental aspects and translational applications
Dr. Silvia Muro, University of Maryland, College Park, MD, USA
The design of targeting and carrier strategies to enable delivery of therapeutic or diagnostic agents to areas of the body requiring intervention is an active research field. Therapeutic and diagnostic targets are often confined to specific regions or tissues in the body, where access may require active transport from the circulation into the subjacent tissue. In addition, once within the tissue or body compartment of interest, most targets of intervention relate to sub-cellular environments, e.g., the cell surface versus different intracellular compartments, further requiring strategies to achieve this goal.
Using polymer nanocarriers functionalized with affinity moieties against single or combined cell-surface receptors, along with additional biological signaling moieties, my laboratory focuses on understanding the parameters that regulate transport of drug delivery vehicles across cellular barriers and into cells of subjacent tissues. We examine these aspects using cell culture models with subsequent validation in laboratory animals to correlate molecular/cellular mechanisms with in vivo outcomes. We investigate the influence exerted on targeting and uptake by drug carrier design parameters (size, shape, avidity, combination targeting, etc.) and parameters that are intrinsic to the physiological system (disease states, flow, receptor epitopes being targeted, modulation of regulatory molecules, etc.). The characterization of these complex physiological and design parameters, along with the understanding of the mechanisms governing the interaction of drugs carriers with the surrounding biological environment, are necessary steps toward achieving efficient drug delivery systems.

IBEC Seminar: Enabling technologies for biofabrication of functional materials and biomimetic environments
2016-11-18 12:00 - 13:00 (Europe/Madrid)
Enabling technologies for biofabrication of functional materials and biomimetic environments
Dr. Alvaro Mata, Director of the Institute of Bioengineering at Queen Mary University of London
The talk will present novel self-assembling and printing technologies enabling the fabrication of 2D and 3D bioactive and/or biomimetic materials for potential application in tissue engineering, regenerative medicine, and in vitro models.
Examples of projects that will be presented include a) a bioactive membrane capable of growing hierarchically-ordered hydroxyapatite structures that resemble those found in human dental enamel; b) a dynamic self-assembling peptide-protein system capable of controllably accessing non-equilibrium to grow tubes and capillaries with potential application in tissue engineering; and c) a simple 3D molecular printing method to create distinct chemical environments ranging from tens of microns to centimeters in size and depth within different types of hydrogels.

IBEC Seminar: Herbert Levine
2016-11-22 15:00 - 16:00 (Europe/Madrid)
Models of individual and collective cell motility
Herbert Levine, Director, Center for Theoretical Biological Physics (CTBP), Rice University, Houston
Eukaryotic cells can move either individually or collectively and this property is crucial for many biological functions. Often cells use directional information to decide on their direction; for single cells this can take the form of chemical or mechanical gradients. For collective motion, additional information can be obtained from neighboring cells through such processes as the contact inhibition of locomotion. Our group develops a variety of computational models for studying actin-based crawling motions. These models range from rather complex and detailed at the single cell levels to simple reduced representations that can handle tissue-level processes. This talk will focus on out recent progress in this direction, specifically on collective chemotaxis of cellular clusters and the role of contact inhibition in the mechanical state of expanding tissues.

IBEC Seminar: Christian A. Nijhuis
2017-01-16 12:00 - 13:00 (Europe/Madrid)
Molecular Diodes with Rectification Ratios of Nearly Six Orders of Magnitude
Christian A. Nijhuis, Department of Chemistry, National University of Singapore
One of the major goals of molecular electronics is to relate the performance and electronic function of molecular devices to the chemical structure and intermolecular interactions of the organic molecules inside them. Molecular electronic devices are complex physical-organic systems that consist of at least two electrodes, the organic component, and two (different) organic/inorganic interfaces. Singling out the contribution of each of these components to the device performance is not straightforward. Besides, fabrication of molecular junctions is still challenging and defects have to be minimized.
During the talk, I will discuss our recent progress of molecular diodes based on self-assembled monolayers (SAMs) of ferrocene-alkanethiolates of the form H(CH2)nFc (Fc = ferrocene) sandwiched between two electrodes. I will discuss in detail how we fabricate the junctions (using the well-characterized “EGaIn”-technique) and characterize our junctions and SAMs. We have investigated the various sources of defects in the junctions caused by the impurities in the SAM precursors,[1] defects in the electrode material,[2] or subtle changes to the electronic[3] and supramolecular structure of the junctions.[4] We used this accumulated knowledge to develop a well-performing diode that blocks the current in one direction of bias, but allows it to pass through in the other, with a difference of a factor of 6.3 x 105.[5,6]
We hope that our findings will help to guide future experiments and to explain why some on paper promising diodes had disappointing performances.[7]
References
1) Jiang, L.; Yuan, L.; Cao, L.; Nijhuis, C. A. J. Am. Chem. Soc. 2014, 136, 1982.
2) Yuan, L.; jiang, L.; Thompson, D.; Nijhuis, C. A. J. Am. Chem. Soc. 2014, 136, 6554.
3) Yuan, L.; Nerngchamnong, N.; Cao, L.; Hamoudi, H.; Del Barco, E.; Roemer, M.; Sriramula, R.; Thompson, D.; Nijhuis, C. A. Nat. Commun. 2015, 6.
4) Nerngchanmnong, N.; Yuan, L.; Qi, D. C.; Jiang, L.; Thompson, D.; Nijhuis, C. A. Nat. Nanotechnol. 2013, 8, 113.
5) Yuan, L.; Breuer, R.; Jiang, L.; Schmittel, M.; Nijhuis, C. A. Nano Lett. 2015, 15, 5506.
6) Chen, X.; Roemer, M.; Yuan, L.; Wei, D.; Del Barco, E.; Thompson, D.; Nijhuis, C.A. submitted
7) Thompson, D.; Nijhuis, C. A. Acc. Chem. Res. 2016, 49, 2061

IBEC Seminar: Giuseppe Battaglia
2017-02-03 10:00 - 11:00 (Europe/Madrid)
Bionic nanoscopic carriers for precision drug delivery
Giuseppe Battaglia, Department of Chemistry and Department of Chemical Engineering, University College London
Getting across biological barriers and deliver therapeutic cargo to the right site is indeed a very challenging task that requires the judicious combination of physiological information with carrier engineering. In the last decade, we have approached this problem, applying a constructionist approach where we mimic biological complexity in the form of design principles to produce functional bionic units from simple building blocks and their interactions. We combine synthetic and supramolecular chemistry to tune inter/intramolecular interactions and self-assembly processes to form dynamic soft materials. Among the different bionic efforts, we have focussed our attention to possibly one of the few that encompasses polymerisation, compartmentalisation and positional self-assembly in the same unit; Polymersomes. These are vesicles formed by the self-assembly of amphiphilic block copolymers in water. We have equipped polymersomes with the critical elements to address the challenges for getting across biological barriers. They have surface engineered to control both attractive (binding) and repulsive (anti-fouling) interaction with proteins and receptors to create systems that can avoid opsonisation and yet target specific cell populations. We have engineered their mechanical properties so as to be flexible and able to penetrate dense tissues exploiting size-exclusion percolation patterns. We have equipped them with both asymmetric topology and enzymes to control their fluid-dynamics and diffusion so as to create chemotactic and active propulsion toward endogenous signalling molecules. Finally, we have engineered their shape and size to guide cellular endocytosis as well as to escape the endocytic sorting accessing and delivering cargo within the cell interior.
I will present our design efforts discussing each structural and functional elements as a function of the respective biological challenge, I will conclude presenting applications where these precision systems are being applied to address challenges in oncology, immunology and neurology.

IBEC Seminar: Stijn Mertens
2017-02-08 12:00 - 13:00 (Europe/Madrid)
Electrochemical surface science of TiO2 rutile (110), graphene and boron nitride
Stijn Mertens, TU Wien, Institute of Applied Physics / KU Leuven, Chemistry Department
The rational design of catalysts and other functional materials requires an atomic-level understanding of their structure and of the interface to supporting surfaces. I will present an in situ electrochemical STM study of TiO2 rutile (110) with atomic resolution. This is achieved using a new wet-chemical cleaning procedure for the substrate and with Pt-Ir tips. If tungsten tips are used, WO3 is spontaneously formed at the tungsten–liquid interface and strongly adsorbs on oxide surfaces below their point of zero charge through an electrostatic mechanism. Under clean conditions, the TiO2 rutile (110) surface shows a bulk-like, unreconstructed structure, which resembles its appearance in vacuum, even though the surface is probably fully hydroxylated.
In the second part of my talk, I will focus on 2D materials graphene and hexagonal boron nitride. By combining electrochemical grafting of diazonium salts with tip-induced nanolithography, nanopatterned sp3 defects can be introduced, opening perspectives towards graphene band gap engineering [1,2]. Hexagonal boron nitride, isoelectronic with graphene, can be grown on Rh(111) and forms a so-called nanomesh superstructure [3], characterized by a 3.2-nm lattice constant and strong electronic corrugation, useful for trapping atoms and molecules. Electrochemical intercalation of hydrogen between the boron nitride layer and the rhodium substrate leads to microscopic flattening within the 2-dimensional material and a macroscopic 10% change in adsorption energy [4].
[1] Greenwood et al., ACS Nano 9, 2015, 5520.
[2] Huynh et al., Nanoscale 9, 2017, 362.
[3] Corso et al., Science 303, 2004, 217.
[4] Mertens et al., Nature 534, 2016, 676.
