Clinical Colloquia
2019-11-15 10:00 - 12:00 (Europe/Madrid) | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Theoretical and practical aspects of biophysiotherapy
Josep Pous, Medical Director at Cematec-Teknon de Barcelona
In this clinical colloquia, the different treatment methods used in Biophysiotherapy such as Multifrequency Laser Therapy, Shock Waves, Modular Electromagnetic Waves, Mechanotherapy, Growth Factors, Stem Cells, will be exposed. The different mechanisms of action will be discussed at the cellular level such as mechanotransduction, mechanotranscription, depolarization of membarane or at the mitochondrial level through REDOX mechanisms, to achieve biological effects at the cellular and tissue levels. Biophysiotherapy aims to apply the possibilities of diagnosis and treatment of the laboratory (biosensors, nanobiosensors, quantum dots) to the medical practice with fewer drugs and fewer surgeries.
Dr. Josep Pous, specialist in Orthopedic Surgery, Traumatology and Rehabilitation, works at Cematec-Teknon of Barcelona (Center of Advanced and Technological Medicine) using the latest technologies in arthroscopy and prosthesis of the shoulder, hip, knee and ankle joints. Dr. Pous is a pioneer in the use of new non-invasive treatments for all musculoskeletal pathology and has incorporated new methods for its integral treatment.
He has been invited to IBEC by Pau Gorostiza

IBEC Clinical Colloquia
2019-11-15 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Theoretical and practical aspects of biophysiotherapy
Josep Pous, Medical Director at Cematec-Teknon de Barcelona
In this clinical colloquium, the different treatment methods used in Biophysiotherapy such as Multifrequency Laser Therapy, Shock Waves, Modular Electromagnetic Waves, Mechanotherapy, Growth Factors, Stem Cells, will be exposed. The different mechanisms of action will be discussed at the cellular level such as mechanotransduction, mechanotranscription, depolarization of membarane or at the mitochondrial level through REDOX mechanisms, to achieve biological effects at the cellular and tissue levels. Biophysiotherapy aims to apply the possibilities of diagnosis and treatment of the laboratory (biosensors, nanobiosensors, quantum dots) to the medical practice with fewer drugs and fewer surgeries.
Dr. Josep Pous, specialist in Orthopedic Surgery, Traumatology and Rehabilitation, works at Cematec-Teknon of Barcelona (Center of Advanced and Technological Medicine) using the latest technologies in arthroscopy and prosthesis of the shoulder, hip, knee and ankle joints. Dr. Pous is a pioneer in the use of new non-invasive treatments for all musculoskeletal pathology and has incorporated new methods for its integral treatment.
He has been invited to IBEC by Pau Gorostiza

IBEC Seminar: Taher Saif
2019-11-22 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Emergent living machines
Taher Saif , Professor, Mechanical Science and Engineering University of Illinois at Urbana-Champaign
Industrial revolution of the 19th century marked the onset of the era of machines that transformed societies. However, these machines cannot self assemble or heal themselves. On the other hand, since the discovery of genes, there is a considerable body of knowledge on engineering living cells. It is now possible to envision biohybrid machines with engineered living cells and scaffolds. These machines may self assemble and emerge from complex interactions between the cells and the scaffolds at various hierarchical levels. In this talk we will present two elementary biohybrid machines. They are both small scale swimmers. One of the swimmers is powered by primary rat cardiomyocytes. These cells are plated without any patterning on a scaffold which consists of a head and a tail. The cells self-orient to maximize scaffold deformation, and synchronize their beating. As a result, the tail deforms periodically and propels the swimmer forward. As a first step towards intelligent machines, the second swimmer consists of optogenetic neurons and muscle cells. It’s scaffold consists of a head and two tails. The muscle cells self assemble into myotubes around the tails, while the neurons are hosted by the head. The neurons spontaneously send out long cables of axons preferentially towards the muscle forming functional neuro functional junctions. They also form a neural network within themselves. Upon shining light, the neurons fire synchronously in a periodic fashion. The muscle contracts and bends the tails to propel the swimmer. This new generation of swimmer powered by neurons paves the way towards intelligent biohybrid machines. The central role of mechanics in the emergence of the biohybrid machines will be highlighted.
Dr Taher Saif received his BS and MS degrees in Civil Engineering from Bangladesh University of Engineering and Technology and Washington State University respectively in 1984 and 1986. He obtained his Ph.D degree in Theoretical and Applied Mechanics from Cornell University in 1993. He worked as a Post Doctoral Associate in Electrical Engineering and the National Nanofabrication Facility at Cornell University during 1993-97. He joined the Department of Mechanical Science and Engineering at the University of Illinois at Urbana-Champaign during 1997. He is curently the Gutgsell Professor in the department. His current research includes tumor micro environment, mechanics of neurons and cardiac cells, development of biological machines, and electro-thermo-mechanical behavior of nano scale metals and semiconductors.
He has been invited to IBEC by Samuel Sánchez

IBEC Seminar: Emilio Parisini
2019-11-26 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Drugging the undruggable: towards the development of selective modulators of cadherin-mediated cell-cell adhesion
Emilio Parisi, Italian Institute of Technology (Milano) and Latvian Institute of Organic Synthesis (Riga)
Cadherins are transmembrane calcium-dependent cell adhesion proteins that mediate cellular adherens junction formation and tissue morphogenesis. Loss of cadherin-mediated adhesion has been implicated in many different steps of tumor progression such as invasion and migration, and is strongly related to cell–cell detachment and metastasis. Altered expression profiles of epithelial E-cadherin (CDH1) and neuronal N-cadherin (CDH2) have often been observed in cancer cells, most notably in the context of the epithelial-to-mesenchymal transition (EMT) process that occurs during cancer progression. Interestingly, while in the majority of carcinomas E-cadherin is down-regulated, in some epithelial ovarian cancer (EOC) cells are characterized by high expression levels of E-cadherin, which facilitates EOC cell proliferation. So far, structural and mutational studies have provided a rather detailed picture of the highly dynamic cadherin homo-dimerization mechanism. However, because of this intrinsic dynamic behavior, the rational design of small ligands targeting cadherin homophilic interactions has proved difficult. We determined the crystal structure of an E-cadherin extracellular fragment in complex with a peptidomimetic compound that partially inhibits cadherin homophilic adhesion. The structure, which is the first and to date the only crystal structure of a cadherin extracellular portion in complex with a small molecule inhibitor, reveals an unexpected binding mode and allows the identification of a druggable cadherin interface. Effective cell−cell adhesion modulators may represent potential anti-angiogenic drugs or pharmaceutical excipients to improve drug delivery across biological barriers.
Emilio Parisini is a Group Leader at the Center for Nano Science and Technology of the Istituto Italiano di Tecnologia (IIT) in Milano. After completing a PhD in Chemistry at the University of Bologna (Italy), he worked at the Universities of Göttingen (Germany), Cambridge (UK) and Harvard (USA). In his laboratory, he studies structure-function relationship in several chemical and biological systems, focusing primarily on the study of the interactions between proteins and their ligands, substrates or inhibitors. His current research interests include the functional and structural characterization of different members of the Cadherin family of cell adhesion proteins and of several different classes of enzymes for diagnostic (biosensors), therapeutic (structure-based drug design) and technological (protein and enzyme engineering) applications.
He has been invited to IBEC by Pau Gorostiza.

PhD Discussions Sessions: Ferran Velasco and Fabio Riefolo
2019-11-29 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Cellulose-based cryogels for long-term culture of pancreatic islets and skeletal muscle tissue
Ferran Velasco, Biosensors for Bioengineering
Islet encapsulation inside traditional hydrogels is one of the most common techniques to study insulin secretion for Diabetes Mellitus studies. However, it’s proved that cells encapsulated in a depth of more than 100 microns die due the lack of nutrient diffusion. As pancreatic islets are spherical aggregations of around 100 microns in diameter, this problem increases exponentially. To solve this problem, in this project we propose the use of new Carboxymethyl cellulose – gelatin biocomposite in combination with cryogelation technique to engineer a new in vitro model to mimic the insulin-mediated skeletal muscle glucose metabolism.
Carboxymethyl cellulose (CMC) is biocompatible, but not mammalian cell-degradable and shows extraordinary elasticity features. Gelatin is able to provide the 3D microenvironment for the proliferation of different cell types and cell-interactive biological activity, very desirable properties for muscle and pancreas tissue scaffold. Cryogelation technique consists in freezing a prepolymer solution at sub-zero temperatures, so water-ice crystals are formed while the material crosslinks. When it’s defrosted, these water-ice crystals lead to “empty” cavities that forms a macroporous and very interconnected scaffold that fits with our needs of morphology and nutrient diffusion.
We first optimize the protocol to achieve the desired morphology; for the pancreatic tissue we achieved a random porosity with high interconnected pores and for the skeletal muscle we fabricate it with an anisotropic structure. We characterize it by stiffness, pore distribution, SEM images and swelling to know its mechanical properties. Then we seed cells in the specific cryogel to characterize its biological behavior depending the cryogel approach used.
Our results are promising for seeding both cell types, as the morphology and pore distributions fits with our needs. These scaffolds show higher nutrient diffusion, good material properties and a better manipulation compared to traditional hydrogels for these tissues.
Photocontrol of Muscarinic Receptors and Applications In Vivo
Fabio Riefolo, Nanoprobes and Nanoswitches
Remote control of physiological functions with light offers the promise of unveiling their complex spatiotemporal dynamics in vivo, and enabling highly focalized therapeutic interventions with reduced systemic toxicity. Optogenetic methods have been implemented in the heart, but the need of genetic manipulation jeopardizes clinical applicability. We present a method to modulate cardiac function with light through a photoswitchable compound and without genetic manipulation. A new light-regulated drug, named PAI, was designed and synthesized to be active on M2 muscarinic acetylcholine receptor (mAChR). PAI can be reversibly photoisomerized between cis and trans conformations under UV and visible light and is able to photocontrol the activation M2 mAChRs in vitro.
We show that PAI has different light-dependent cardiac effects in a mammalian animal model. Finally, we demonstrate the reversible, real-time photocontrol of cardiac function in translucent wildtype tadpoles: PAI induced bradycardia and this effect could be reversibly switched using UV and visible illumination. PAI can also effectively activate M2 receptors using two-photon excitation with near-infrared light, which overcomes the scattering and low penetration of short-wavelength illumination. Such a new approach may enable enhanced spatial and temporal selectivity for cardiovascular drugs.

PhD Thesis Defence: Roberto Paoli
2019-12-09 11:00 - 13:00 | Facultat de Física – Sala de Graus Antiga
Cell Culture interfaces for different organ-on-chip applications: from photolithography to rapid-prototyping techniques with sensor embedding
Roberto Paoli, Nanobioengineering group

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.

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 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.

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
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.
