Institute for Bioengineering of Catalonia

PhD Discussions Sessions: Maria Arista
2019-12-13 00:30 - 14:00 (Europe/Madrid) | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Super-resolution microscopy as a powerful tool for understanding the formation and inhibition of influenza virus structures in mammalian cells
Maria Arista, Nanoscopy for Nanomedicine
Super-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) .
Influenza 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.
Here, 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.
Moreover, 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.

PhD Discussions Sessions: Maria Arista
2019-12-13 00:30 - 14:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Super-resolution microscopy for understanding the formation and inhibition of influenza virus structures
Maria Arista, Nanoscopy for Nanomedicine
Super-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) .
Influenza 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.
Here, 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.
Moreover, 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.

IBEC Christmas Celebration 2019
2019-12-19 18:00
We’re delighted to invite you once again to the best IBEC Christmas Party Ever!

Thursday 19th December · Fifteen Restaurant, PCB
As usual, there’ll be a chance to take part in a charity event to raise money for some very good causes. The more 1€ raffle tickets you buy during dinner, the more likely you are to win one of the fabulous prizes provided by our sponsors.
With all this, plus food, drink, music and some fun surprises, the IBEC Christmas Party promises once again to be a fabulous way to kick-start the festive season. We’re counting on you to make the party go with a swing!
18:00 – 20:00 Team building activity
20:00 – 21:30 Sale of raffle tickets
20:00 – 22:00 Buffet dinner
22:00 Raffle and party
00:30 End

Please register before 16th December here

PhD Thesis Defence: Aida Garrido
2020-01-15 11:30 - 13:00 | Sala de Graus – Campus de Bellvitge
Control òptic de receptors endògens i excitabilitat cel·lular amb llum
Aida Garrido, Nanoprobes and nanoswitches group
L’estudi electrofisiològic i d’imatge de l’activitat neuronal en temps real requereix una gran resolució espacial i temporal. Ambdós trets es poden aconseguir amb la precisió, velocitat i control remot que permet la llum. En aquesta tesi es descriu la caracterització de nous fotocommutadors dirigits a fotosensibilitzar receptors endògens de glutamat i estratègies per la millora de les seves característiques òptiques.
Els primers fotoconmutadors descrits capaços de controlar amb llum l’activitat de canals endògens de glutamat son eficaços en altres aproximacions experimentals com ara en la inducció amb llum de potencials d’acció en neurones en cultiu, en cultius organotípics d’hipocamp de rata o in vivo en larves de Xenopus electroporades, a nivell d’un grup neuronal, d’una única neurona o d’una única espina sinàptica. Modificant la part reactiva del fotocommutador, som podem controlar espacialment la conjugació mitjançant patrons d’il·luminació.
Canviant l’estructura química s’aconsegueix un fotocommutador actiu en el rang visible de llum i alhora extremadament ràpid. Fet que el fa ideal pel control de sinapsis ultra ràpides com ara les encarregades de codificar el so en la còclea. El disseny racional d’altres modificacions químiques en fotocommutadors de receptors de glutamat (LiGluRs) obre les portes al disseny de molècules sensibles a l’activació per 2 fotons. L’estimulació de 2 fotons amb làsers polsats de llum infraroja comporta importants avantatges com ara l’augment de la capacitat de penetració en teixit i una disminució de possibles danys degut a una sobreexposició a la llum. Característiques molt útils per estudis in vivo. Modificacions químiques dels fotocommutadors comporten altres modificacions en les seves característiques fotodinàmiques. Per aquest motiu, hem desenvolupat una estratègia de conjugació de fluoròfors col·lectors de llum que mitjançant RET transfereixen la seva energia al cromòfor (fotocommutador), modificant-ne les característiques espectrals.
Es demostra que cromòfors no conjugables permeten controlar l’activitat neuronal. Amb diversos avantatges respecte l’azobenzè clàssic: els azobenzens cíclics reverteix l’estabilitat i en conseqüència l’activitat de la molècula; i els estilbens permeten l’activació irreversible però no foto-destructiva de la molècula original, evitant així la creació de foto-productes.
En conclusió, en aquesta tesi es presenten noves molècules i estratègies de disseny per al control de la neurotransmissió sense necessitat de modificacions genètiques.

PhD Thesis Defence: Aida Garrido
2020-01-15 11:30 - 13:00 | Sala de Graus – Campus de Bellvitge
Optical control of endogenous receptors and cellular excitability with light
Aida Garrido, Nanoprobes and nanoswitches group
Light-controlled manipulation of neuronal activity has transformed the field of neurobiology. Light provides temporal and spatial resolution over activation or inhibition of targeted populations of neurons, one single neuron or single synapses. Such precision could be achieved with optogenetics, which is based on the over-expression of light-sensitive proteins, but it requires gene therapy and often alters cellular physiology. An alternative to optogenetics is offered by photopharmacology (the development of light-regulated drugs or photoswitches), which can operate on endogenous receptors without genetic manipulation. Several new photoswitches are described in this thesis to improve their pharmacological and optical properties.
In photopharmacology, azobenzene is the most commonly used light switch. Photoswitchable tethered ligands (PTLs) are tri-modular molecules able to anchor to target receptors and alter their function by switching the azobenzene group. In the first chapter we demonstrate the ability to target endogenous receptors of hippocampal neurons and olfactory bulb neurons from Xenopus larvae. The chemical strategy used was to introduce a highly reactive anchoring group to a PTL with similar structure to the reported MAG compound used in the light regulated glutamate receptor, LiGluR. These new kind of PTLs were called “Targeted Covalent Photoswitches” (TCPs).
The promiscuity of the reactive group of TCP limits the possibility to spatially confine the drug conjugation. Thus, we designed a photolabile TCP that can be conjugated to its target with a specific wavelength, and then be photoswitched at another wavelength.
Despite the advantages of all molecules described above, they share a common limitation: the activation wavelength of azobenzene is in the UV-violet range. Increasing the push-pull effect at the azobenzenic core by adding different substituents, we achieved a TCP derivative activatable at the visible range and ultrafast relaxing. In this way a single wavelength of stimulation can be used. Both features make them great candidates to control ultrafast neurotransmission processes such as the ones implicated in sound coding in the cochlea. We demonstrated in a gerbil animal model the capacity of this blue-activated TCP to photosensitize native receptors of adult gerbil cochlea. This first proof of concept opens new possibilities to develop optical cochlear implants for the treatment of hearing loss avoiding gene therapy.
Chemical substitutions can also be rationally designed to enhance two-photon (2P) absorptivity without modifying the dynamics of photoswitches. In the third chapter we described two new 2P enhanced MAG derivatives to photocontrol LiGluR. We validated their properties with an all-optical approach, by recording calcium induced neuronal responses in organotypic hippocampal slices, and in vivo in Caenorhabditis elegans. The combination of slow relaxation lifetime and enhanced 2P absorptivity is translated into an accumulation of the active isomer of the photoswitch that successfully enhances its functional effect even at low illumination power.
Another way to spectrally modify the characteristics of a chromophore while avoiding mutation screening and new synthetic processes is by using light-harvesting fluorophores. Spectral overlapping of fluorophore emission and chromophore absorption broadens its activation spectrum. By means of chemical protection and deprotection, we orthogonally control the conjugation of fluorophores and photoswitches. This is the first demonstration of light-harvesting strategy for optogenetics and photopharmacology.
Finally, we describe the use of novel PCLs containing chromophores other than linear azobenzene for the light-controlled activation of hippocampal neurons. Cyclic azobenzenes reverse isomer thermal stability and consequently also the activity of the photoswitch. On the other hand, stilbenes allow the irreversible but non-photo-destructive activation of the original molecule, thus avoiding the creation of photo-products.
In conclusion, this thesis puts forward several advances in the photochromism and pharmacology of photoswitches for the control of neurotransmission without need of genetic manipulation.

IBEC Seminar: Anotine Huet
2020-01-16 12:00 - 14:00 | Torre I Sala 3 Planta -1, Carrer Baldiri Reixac 4-8, Barcelona
Cochlear optical stimulation of the auditory pathway
Antoine Huet , Institut für Auditorische Neurowissenschaften, Universitätsmedizin Göttingen
Optical stimulation of spiral ganglion neurons (SGNs) in the ear for coding sound information provides an interesting alternative to electrical stimulation that is used in current cochlear implants for hearing restoration. As light can be conveniently confined in space, optical stimulation promises not only to increase the number of independent stimulation channels, but also potentially to restore temporal response of SGNs which are phase-locked to the periodicity of the sound. Sensitizing SGNs to light can be achieved either by optogenetic manipulation for expressing a light-sensitive protein, or by photopharmacological manipulation of receptors native to the cochlea.
Pioneering studies have established proof of principle of optical cochlear stimulation to restore hearing in rodent models of deafness (Hernandez et al, 2014; Wrobel, Dieter et al, 2018). More recent work from the last 2 years have demonstrated i) improvement of frequency selectivity in response to light-over electrical stimuli (Dieter et al, 2019), and ii) activation of the auditory pathway by faster opsins (i.e. shorter closing kinetics) which are more suitable for fast spiking SGNs (Mager, Lopez de la Morena et al, 2018, Keppeler et al, 2018). Finally, ongoing work, in collaboration with the team of Pau Gorostiza, is showing than a photopharmacological approach targeting AMPA receptors could be used to optically activate the auditory pathway with performance similar to current optogenetic tools.
Dr. Antoine Huet is a postdoctoral fellow in the Institute for Auditory Neuroscience (University Medical Center Göttingen) under the supervision of Prof. Dr. Tobias Moser. Dr Huet received his BS degree in Audiology from the Institut libre Marie-Haps (Brussel, Belgium) and MS degree in Audiology and auditory neuroscience from the University of Montpellier 1 (Montpellier, France). He obtained his PhD degree in Chemical and biological science for Health from the University of Montpellier 1 (Montpellier, France). He worked as a Postdoctoral fellow under the supervision of Pr. J-L. Puel and Jerome Bourien, PhD in the Institut des neurosciences de Montpellier (INSERM U1051, France) till May 2018. After, he joined the laboratory of Pr. Dr. Tobias Moser in the Institute for Auditory Neuroscience from the University Medical Center Göttingen (Germany). His current research interest include the development of viral transfer of suitable ChR variants into spiral ganglion neurons and of multichannel optical stimulation using cochlear implants with arrays of microscale light emitting diodes and waveguides, characterizing neuronal responses along the auditory pathway using physiological and behavioral methods. Thus, to finally compare optogenetic to acoustic and electric stimulation.
He has been invited to IBEC by Pau Gorostiza

IBEC PhD Discussions Complementary Skills Session: Some philosophical & sociological issues about present science: from the privatization of science to the production of ignorance
2020-01-31 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Some philosophical & sociological issues about present science: from the privatization of science to the production of ignorance
Eduard Aibar – Professor of Science and Technology Studies at the Arts & Humanities Department, Universitat Oberta de Catalunya (UOC)
This seminar will present some basic points of the recent view of science produced by fields like the philosophy of science, the sociology of science and the history of science. We will highlight the strong contrast between this view and the traditional view of science – still dominant in many areas of society – particularly around matters like the scientific method, the evolution of science and the role of controversies. We will also discuss a few important phenomena of contemporary science: the productivist view of research evaluation, the privatization of scientific knowledge and, finally, agnotology – the systematic production of ignorance.
Eduard Aibar is professor of Science and Technology Studies at the Arts & Humanities Department, Universitat Oberta de Catalunya (UOC). He has been the director of the Internet Interdisciplinary Institute and former vice-president for research at UOC. He is currently leading a research group on Open Science and Innovation. His research has focused on the interaction between scientific and technological development and organizational and social change in areas such as eGovernment, town planning and the Internet. He has recently led two research projects on Wikipedia and the public communication of science.
For more info see: https://www.uoc.edu/webs/eaibar

HealthTECH World Cancer day 2020
2020-02-03 10:00 - 13:00
HealthTECH World Cancer day 2020

HealthTECH World Cancer day 2020 es un evento organizado en el marco del Día Mundial del Cáncer donde se darán a conocer las últimas innovaciones en materia de NANOMEDICINA contra el CÁNCER, con temas que van desde el diagnóstico precoz, la liberación controlada de fármacos o la radioterapia con nanopartículas.
Durante esta jornada, expertos en NANOMEDICINA de diferentes campos, expondrán los últimos adelantos y nos darán la oportunidad de descubrir el generador de progreso que la NANOMEDICINA significa para la salud como creador de nuevas oportunidades en el diagnóstico y el tratamiento del cáncer.
Iniciado en 2013 bajo el nombre de NANO WORLD CANCER DAY, este evento ha sido organizado por la Plataforma Tecnológica Europea sobre Nanomedicina (ETPN) y actualmente está respaldado por el Proyecto Europeo NOBEL (Smarter HealthTech in Europe). En España lo organiza NANOMED Spain y se realiza de manera simultánea en diferentes países de toda Europa.
Día y lugar del evento:
Lunes, 3 de febrero · 10:00 h
Sala Pau Viladiu
Hospital Duran i Reynals
Avda. de la Granvia de l’Hospitalet, 199
08908 L’Hospitalet de Llobregat, Barcelona
Asistencia gratuita, necesario registrarse antes del 29 de enero en: events.ibecbarcelona.eu/hwcd2020

IBEC Seminar: Andela Saric
2020-02-06 11:00 - 13:00 | Sala Félix Serratossa, Parc Científic de Barcelona, Barcelona, Spain
How to build a biological nanomachine
Andela Saric , University College London
The molecular machinery of life is largely created via self-organisation of individual molecules into functional larger-scaled structures. Such processes are multi-scale in nature and constantly driven far from thermodynamic equilibrium. Our group develops minimal coarse-grained computer models to help understand how the assembly of a large number of macromolecules results in a functional nanomachine, as well as how such processes can go wrong, leading to diseases.
Here I will discuss the physical mechanisms behind two key biological nanomachines that operate via protein assembly – active elastic ESCRT-III filaments that remodel and cut cell membranes and split cells in two, and bacterial mechanosensitive protein channels that convert mechanical signals into chemical. I will discuss the model development, simulation results, and the mapping of the simulation data to in vivo experiments. Beyond their biological context, our findings can guide the design of artificial structures that are able to manipulate cell membranes and perform work at the nanoscale.
Andela is an Associate Professor in the Department of Physics and Astronomy and Laboratory for Molecular Cell Biology at University College London. She obtained her PhD from Columbia University in 2013, followed by postdoctoral research at the University of Cambridge. Andela works in the area of computational biological physics, developing minimal models to study biological assembly and cell remodelling. She is a recipient of the ERC Starting Grant, Royal Society University Research Fellowship, and HFSP Cross-disciplinary Fellowship.
She has been invited to IBEC by Josep Samitier

IBEC Seminar: Andela Saric
2020-02-06 11:00 - 13:00 | Felix Serratosa, Baldiri Reixac, 10-12, Barcelona, Spain

IBEC Seminar: Gema Esquiva
2020-02-07 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Alteraciones en el sistema melanopsínico en la retinosis pigmentaria y durante el proceso de envejecimiento
Gema Esquiva , Universitat d’Alacant
La retinosis pigmentaria es la degeneración hereditaria de la retina más frecuente, siendo la cuarta causa de ceguera en el mundo. Además, en esta enfermedad, se producen alteraciones en los ritmos circadianos, esenciales para llevar una vida saludable, ya que estas alteraciones se relacionan con aumento en el estrés, insomnio, depresión y muchas otras patologías. La regulación de los ritmos circadianos se lleva a cabo a través de un tipo de células ganglionares de la retina, las células melanopsínicas.
En este trabajo se describen los diferentes tipos de células ganglionares melanopsínicas en la retina humana, en la retina de rata y en un modelo animal de retinosis pigmentaria. Además, evaluamos los cambios morfológicos y de densidad producidos en estas células, y estudiamos los efectos producidos en los patrones circadianos durante la progresiva degeneración retiniana que ocurre en esta enfermedad. También evaluamos el efecto neuroprotector de la administración de melatonina exógena.
El estudio morfológico de la retina en estos animales puso de manifiesto la existencia de 3 tipos de células melanopsínicas en rata de las cuales únicamente dos habían sido descritas hasta el momento. Por otro lado, observamos una disminución y degeneración de estas células, asociada a la retinosis pigmentaria y al envejecimiento.
Los resultados obtenidos mediante técnicas electrorretinográficas y mediante los registros de temperatura corporal y de actividad locomotora desvelaron que los animales modelo de retinosis pigmentaria tenían menor respuesta visual y una alteración de los ritmos circadianos. Los animales modelo de retinosis pigmentaria tratados con melatonina mostraron mayor respuesta visual y mejor regulación de los ritmos circadianos que los animales modelo sin tratar.
Estos resultados indican que en modelos de retinosis pigmentaria la degeneración de los fotorreceptores clásicos se acompaña de un proceso de remodelación de la retina interna que afecta al sistema melanopsínico. Deducimos que la alteración en los ritmos circadianos se manifiesta a partir de las alteraciones observadas en la densidad y en los procesos dendríticos de las células ganglionares melanopsínicas. En este sentido, la melatonina ejerce un efecto neuroprotector sobre los fotorreceptores en degeneración, conos, bastones y células melanopsínicas de la retina. Por otro lado, tras el estudio de las retinas humanas concluimos que el envejecimiento se asocia con una pérdida de densidad y arborización dendrítica de las células melanopsínicas lo que posiblemente explica la aparición más frecuente de trastornos del ritmo circadiano en personas de edad avanzada.
Ha sido invitada al IBEC por Pau Gorostiza
