Institute for Bioengineering of Catalonia

IBEC Seminar: Miguel Holgado
2022-04-01 10:00 - 13:00 (Europe/Madrid) | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Technologies for highly multiplexed in-vitro diagnostic systems and organ on chips. Cases studies for COVID-19 and neurodegenerative diseases
Miguel Holgado, Centro de Tecnología Biomédica-Universidad Politécnica de Madrid and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
Technologies for biomarkers screening are of very high importance, particularly when they are reliable, cost effective, easy to use for measuring multiples biomarkers in a single diagnostic KIT working with real biological samples such as serum, saliva, wastewater or culture medium. In this paper we report technologies for the development of a highly multiplexed kit for detecting biomarkers of COVID19 in serum, saliva[1] and wastewater analyzing their correlation with the severity of the COVID19 and showing relevant figures about the severity (90 patients in serum), immunity (200 volunteers in saliva donating sample every 10 days in three months), and wastewater. This technology has also demonstrated for measuring particular proteins of the SARS-COV-2 in wastewater, which results have been compared with Polymerase Chain Reaction. Recently we are using these technologies for detecting Alzheimer Disease (AD) biomarkers in serum.
In concrete, we have achieved to detect the total tau protein at the level of 10 pg mL-1 in serum as a biomarker for early detection of the AD[2]. Other biomarkers are also under development right now. In this term, the use of advanced in vitro diagnostic systems with organ-on-chip based technologies are of a high relevance because can be used for monitoring relevant biomarkers secreted by the cells, tissues or biopsies in these types of bioreactors. We have recently developed microfluidic chips acting as bioreactors for neuronal circuits on a chip for biological network monitoring[3] and brain slice-on-a-chip for organotypic culture and effective fluorescence injection testing[4]. Cultured neuronal networks (CNNs) are a robust model to closely investigate neuronal circuits’ formation and monitor their structural properties evolution. Typically, neurons are cultured in plastic plates or, more recently, in microfluidic platforms with potentially a wide variety of neuroscience applications. As a biological protocol, cell culture integration with a microfluidic system provides benefits such as accurate control of cell seeding area, culture medium renewal, or lower exposure to contamination. In this paper it is presented a novel neuronal network on a chip device, including a chamber, fabricated from PDMS, vinyl and glass connected to a microfluidic platform to perfuse the continuous flow of culture medium.
As a step forward, we employ this technology as an alternative brain slice-on-a-chip, integrating an injection system inside the chip to dispense a fluorescent dye for long-term monitoring. Hippocampal slices are cultured inside these chips, observing fluorescence signals from living cells, maintaining the cytoarchitecture of the slices. Having fluorescence images of biological samples inside the chip demonstrates the effectiveness of the staining process using the injection method avoiding leaks or biological contamination. The technology developed in this study presents a significant improvement in the local administration of reagents within a brain slice-on-a-chip system, which could be a suitable option for organotypic cultures in a microfluidic chip acting as a highly effective bioreactor.

[1] Developing an Optical Interferometric Detection Method based biosensor for detecting specific SARS-CoV-2 immunoglobulins in Serum and Saliva, and their corresponding ELISA correlation. Sensors & Actuators: B. Chemical 345 (2021)
[2] A new optical interferometric in-vitro detection for Alzheimer´ disease diagnostic in Serum. To be published elsewhere.
[3] Neural circuits on a chip for biological Network Monitoring. Biotechnology Journal 2021. https://doi.org/10.1002/biot.202000355
[4] Alternative Brain Slice-on-a-Chip for Organotypic Culture and Effective Fluorescence Injection Testing. Int. J. Mol. Sci. 2022, 23, 2549.

IBEC Seminar: Miguel Holgado
2022-04-01 10:00 - 13:00 | IBEC, floor 11, tower i

IBEC Seminar: Iris Batalha
2022-05-13 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Nanotherapeutics – ‘How we sometimes underestimate the influence of little things’
Iris L. Batalha, Institute for Bioengineering of Catalonia (IBEC)
Deaths caused by infections from antibiotic-resistant bacteria are expected to skyrocket over the next decades, with a staggering 10 million deaths per year projected for 2050. Treating infections by intracellular pathogens, such as M. tuberculosis, is ‘a perfect storm’. The WHO revealed that while some 50 new antibiotics and 10 biologics are under development, only half of those target WHO-priority pathogens and the majority have very limited benefits when compared to existing antibiotics. Reformulating existent drugs in nanocarriers may help achieving enhanced efficacy and safety while reducing dose frequency, by providing temporal and localised control of drug exposure. In this talk, I will present my work on the synthesis of dual-drug tunable nanoparticle-based antibiotics, which showed increased bacterial killing efficacy in a zebrafish larval model of mycobacterial infection when compared to free drugs at the same concentration. In addition, nanoparticles were able to efficiently penetrate mycobacterial cords and granulomatous lesions – shielded regions of difficult access by free drugs, improving the therapeutic effect.

Iris Batalha is currently a Junior Leader Research Fellow at the Institute for Bioengineering of Catalonia (IBEC) in Barcelona, a Panel Tutor in Nanotherapeutics at the University of Cambridge Institute of Continuing Education, a freelance Senior Innovation Consultant at Inspiralia (Spain and USA), a Co-founder, Director and Editor-in-Chief of the non-profit organisation Women Ahead of Their Time (WATT), and a Research Associate at Peterhouse College. From 2017 to 2020, she was a joint Research Associate at the Department of Engineering Nanoscience Centre and Department of Medicine Molecular Immunity Unit, University of Cambridge. From 2014 to 2017, she worked at the Department of Chemical Engineering and Biotechnology, University of Cambridge, and the biopharmaceutical company MedImmune/Astrazeneca, followed by a brief experience as a healthcare/pharmaceutical consultant. Her research interests and expertise lie in medical and pharmaceutical research and development, particularly in the fields of nanobiotechnology, bio-inspired materials, downstream processing, formulation and drug delivery.

Sala Baobab, Tower I, 11 Floor, IBEC

Meet the editors: Christine Horejs and Kristy Hooper
2022-06-07 15:00 - 17:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Come and meet the editors of Nature Reviews Bioengineering and The Company of Biologists: Christine Horejs and Kirsty Hooper. In this seminar we will hear about the latest updates in their journals and we will discuss the future of scholarly publishing and the open access models.

Sala Baobab, Tower I, 11 Floor, IBEC

Last minute Seminar: Laura Suter-Dick
2022-06-27 12:30 - 13:30 | Sala Baobab, Tower I - 11th floor
Liver and Kidney: 3D-in vitro systems for disease modelling and biomarker discovery
Prof. Laura Suter-Dick
FHNW University of Applied Sciences and Arts Northwestern Switzerland School of Life Sciences, Institute for Chemistry and Bioanalytics a Basel.

IBEC Seminar: Myriam M. Chaumeil
2022-09-09 10:00 - 12:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Imaging metabolism in neurological disorders

Associate Professor in Residence, Departments of Physical Therapy and Rehabilitation Science & Radiology and Biomedical Imaging, UCSFInvestigator, Quantitative Bioscience Institutes (QBI)Lab website : Chaumeil Lab, UCSF

Our lab works on developing and biologically validating magnetic resonance (MR)-based metabolic imaging approaches using animal models of neurological diseases (such as genetically-engineered or toxin-induced). In this talk, I will present how optimized acquisitions strategies, based mostly on the hyperpolarized DNP-MR technology, can be used for improved diagnosis and treatment monitoring of neurological diseases, including multiple sclerosis, chronic traumatic encephalopathy and Alzheimer’s disease. I will also show how we use metabolomics approaches to identify potential pathways modified in disease, and normalized with treatment, with an example focusing on interneuron transplantation as a treatment for epilepsy.

Dr. Chaumeil is an Associate Professor in Residence in the department of Physical Therapy & Rehabilitation Science and Radiology & Biomedical Imaging at UCSF, a faculty member of three graduate programs (UCSF/UC Berkeley BioEngineering; UCSF Biomedical Science and UCSF Rehabilitation Science), and an investigator in the Quantitative Biosciences Institute. Her research focuses on developing new neuroimaging methods to improve the diagnosis and monitoring of neurological disorders, such as Alzheimer’s disease, Multiple Sclerosis or vascular dementia. She is a Junior Fellow of the International Society of Magnetic Resonance in Medicine, and has been recently elected on the board of the ISMRM Hyperpolarized Study group. Dr. Chaumeil grew up in the south of France, and received her engineer degree and her PhD degree in Paris, before moving across the world to California to join UCSF.

Sala Baobab, Tower I, 11 Floor, IBEC

IBEC Seminar: David Odde
2022-10-05 10:00 - 12:00
Differential migration mechanics and immune response of glioblastoma subtypes
David Odde, Dept. of Biomedical Eng., U. Minnesota
Glioblastoma remains a deadly cancer driven by invasion of tumor cells into the brain. Transcriptomic analyses have revealed distinct molecular subtypes, but mechanistic and targetable differences that explain clinical differences are not clear. Using a state-of-the-art immunocompetent mouse model for glioblastoma – where tumors are induced by injection of plasmids containing human glioblastoma subtype-defining genetic drivers in a wild-type background – we found that, as predicted by the motor-clutch model for cell migration (Klank et al., Cell Rep, 2017), mesenchymal glioma cells are more spread, generate larger traction forces, and migrate faster in brain tissue compared to proneural cells. Despite their fast migration and comparable proliferation rate in vitro, mice with mesenchymal tumors live longer than mice with proneural tumors, which was correlated with an immune response in the mesenchymal mice that included T cell-mediated killing of cancer cells, similar to human tumors. Thus, mesenchymal tumors have aggressive migration, but are relatively immunologically ‘hot’ which suppresses net proliferation, features which are captured by our Brownian Dynamics tumor simulator (Klank et al., Conv Sci Phys Oncol, 2018). These two features counteract each other and may explain the lack of a strong survival difference between subtypes clinically, while also opening up new opportunities for subtype-specific therapies.

David Odde is the Medtronic Professor of Engineering in Medicine at the University of Minnesota. Trained as a chemical engineer at the University of Minnesota and Rutgers University, Odde joined the newly created Department of Biomedical Engineering at the University of Minnesota in 1999 where he is a professor and Associate Director for Strategic Research Initiatives in the Institute for Engineering in Medicine. In his research, Odde’s group builds computer models of cellular and molecular self-assembly and force-generation-dissipation dynamics, and tests the models experimentally using digital microscopic imaging of living cells ex vivo and in engineered microenvironments. His group seeks to bring an engineering approach that uses physics-based modeling and analysis to understand, predict, and control disease outcomes (oddelab.umn.edu). Dr. Odde is an elected Fellow of the American Institute for Medical and Biological Engineering (AIMBE), the Biomedical Engineering Society (BMES), the International Academy of Medical and Biological Engineering (IAMBE), and the American Association for the Advancement of Science (AAAS) and is the Director of the Physical Sciences in Oncology Center at the University of Minnesota (psoc.umn.edu), which is focused on modeling the mechanics of cancer cell migration in biologically relevant contexts.

IBEC Seminar: Conrado Aparicio
2022-10-14 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Peptides and bioinstructive polymers on surfaces for prevention of oral infections
Conrado Aparicio, Faculty of Odontology, UIC Barcelona and Associated Researcher – IBEC
Oral infections are the most prevalent infectious diseases worldwide. We have explored bioinspired modification of surfaces of restorative/regenerative materials and implants as well as dental tissues to address oral infections by harnessing the biomolecular toolbox –oligopeptides, proteins, recombinamers, … and thus, mitigating the worldwide threat of antimicrobial resistance.
One of our strategies aimed at exploiting secondary structure and self-assembly of anti-biofilm peptides and recombinamers to increase anti-biofilm potency vs relevant oral biofilms and to form highly hydrophobic interfaces to obtain dual-action surfaces to address infection in dental peri-tisular and peri-implant sites.
Alternatively, we have found inspiration in the natural junction at the tooth-oral mucosa interface. Teeth, long-lasting percutaneous organs, feature soft tissue attachment through adhesive structures, hemidesmosomes, in the junctional epithelium basement membrane adjacent to teeth. This soft tissue attachment prevents bacterial infection of the tooth despite the rich – and harsh – microbial composition of the oral cavity. Consequently, we have tapped basement membrane peptides known to engage specific integrins as well as synthesized new bioinstructive photocurable resins that stimulate formation of hemidesmosomes on synthetic and natural surfaces.
We recently have also combined those strategies with immunomodulatory regulation to reduce inflammation triggered by pathogenic biofilms causing oral infections.

Dr. Conrado Aparicio is Professor at the Department of Odontology of UIC Barcelona – Universitat International de Catalunya, Spain. He is associated researcher at IBEC-Institute for BioEngineering of Catalonia and elected fellow of the AIMBE-American Institute for Medical and Biological Engineering.
Dr. Aparicio is a materials scientist and engineer by training. After starting his academic career at the Technical University of Catalonia (UPC) he moved to the University of Minnesota (UMN) where he spent 12+ years in the Department of Restorative Sciences, and was the Deputy Director of the MDRCBB-Minnesota Dental Research Center for Biomaterials and Biomechanics. Last year Professor Aparicio returned to his hometown, Barcelona, as FBA-BIST-UIC fellow.
For two decades he has carried out multidisciplinary research on bioinspired biomaterials and interfaces for directing biological responses to repair/regenerate bone and oral mucosa as well as to prevent bacterial infections for dental applications. Using inspiration from nature’s molecules and structures, his team designs and develops bioactive surfaces using supramolecular assembly and enabling spatial-temporal control of bioactive responses.
He has published 130+ research papers and has lectured around the World on bioactivation of synthetic biomaterials for reparative and regenerative dentistry and medicine. He is co-inventor of multiple patents, one of them licensed and marketed by a dental implant company. He has been awarded multiple national and international research projects from US and EC agencies, foundations and corporations, in interdisciplinary collaborations between academic and corporate engineers, biologists, and clinicians.

IBEC Seminar: Felipe Galvez-Cancino (canceled)
2022-11-02 15:30 - 17:30 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain

IBEC Seminar: Takashi Hiiragi
2022-11-09 16:00 - 18:00 | Sala Baobab, Tower I - 11th floor
Multicellular coordination in context
Takashi Hiiragi, Hubrecht Institute, The Netherlands
A defining feature of living systems is the capacity to break symmetry and generate well-defined forms and patterns through self-organisation. Our group aims to understand the design principle of multicellular living systems using early mouse embryos as a model system. We developed an experimental framework that integrates biology, physics and mathematics, to understand how molecular, cellular and physical signals are dynamically coupled across the scales for self-organisation. I will discuss our ongoing work investigating the coordination of developmental programmes in space and time.

Takashi Hiiragi is group leader at the Hubrecht Institute. The Hiiragi group aims to understand what defines multi-cellular living systems. In particular, the group studies the design principle of tissue self-organization, using early mammalian embryos as a model system. To this end, they developed an experimental framework that integrates biology, physics and mathematics. Their recent studies led to a model in which feedback between cell fate, polarity, and cell and tissue mechanics underlies multi-cellular self-organization. The group adopts a wide variety of experimental strategies including embryology, genetics, advanced microscopy, biophysics, engineering and theoretical modelling, in order to address fundamental questions in cell and developmental biology.

IBEC Seminar: Astrid Viciano
2022-11-11 10:00 - 12:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Is the price of pharmaceutical drugs justified?
Astrid Viciano, IBEC
10 euros, 1000 euros, or rather 1 million? Many new medicines that have recently reached the market are prohibitively expensive. But are these prices justified? Science reporter Astrid Viciano has investigated the high prices of innovative therapies. For these investigations, she received a number of European journalism stipends.
Viciano will explain how the pharmaceutical industry calculates prices for new drugs, and who currently determines the costs for new medications in different healthcare systems. Looking into different, concrete examples such as the drug Zolgensma for the treatment of spinal muscular atrophy, she will point out how drugs are currently developed and approved, and how medications for orphan diseases are developed. Moreover, looking into historic examples such as insulin, she will look into why access to potentially life-saving drugs is still not guaranteed in all regions of the world, an urgent problem the Covid-19 pandemic has highlighted in the past two years.

Dr. Astrid Viciano has been working as a science journalist for German national media such as Süddeutsche Zeitung, Die Zeit, Spiegel, and GEO for more than 20 years.
She has worked in a variety of European cross-border teams, focusing on in-depth investigative science reporting. From 2012 to 2016, she worked as a freelance reporter from Paris, and from 2009 and 2011 in Los Angeles. She has published articles in German, English, Dutch and Spanish. Viciano has won several national and international journalism awards, grants, and fellowships.
Astrid Viciano is a medical doctor with a doctorate in immunology and virology and also has an M.A. in Specialized Journalism (USC Annenberg ’11). Currently she is „journalist-in-residence“ at IBEC. She holds the Spanish and German nationalities.

Sostenibilidad en el PCB (spanish)
2022-12-02 10:00 - 14:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
En este seminario, Glòria Pladellorens, jefa de Calidad, Seguridad y Medio Ambiente del PCB, nos explicará todas las acciones que se están llevando a cabo desde PCB para avanzar hacia un parque científico más sostenible.
El comité de sostenibilidad ha invitado a Glòria a dar esta charla que será una muy buena oportunidad para resolver todas esas dudas que nos planteamos y compartir nuestras inquietudes e ideas para tener un entorno de trabajo más sostenible.

This seminar will be in Spanish, a translated report will be prepared and distributed among the non-Spanish speakers.
All members of research groups in the process of My green lab certification are strongly encouraged to attend.

IBEC Seminar: Xavier Rovira-Clavé
2022-12-21 11:30 - 13:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Epitope barcoding and subcellular high-plex imaging reveal clonal tumor patch behaviors
Xavier Rovira-Clavé, PhD
Intratumoral heterogeneity is a seminal feature of human tumors contributing to tumor progression and response to treatment. Current technologies are still largely unsuitable to accurately track phenotypes and clonal evolution within tumors, especially in response to genetic manipulations. In this seminar I will present our recent development of epitopes for imaging using combinatorial tagging (EpicTags), which we coupled to multiplexed ion beam imaging (EpicMIBI), for in situ tracking of barcodes within tissue microenvironments. Using EpicMIBI, we dissected the spatial component of cell lineages and phenotypes in xenograft models of small-cell lung cancer. We observed emergent properties from mixed clones leading to the preferential expansion of clonal patches for both neuroendocrine and non-neuroendocrine cancer cell states in these models. In a tumor model harboring a fraction of PTEN-deficient cancer cells, we observed a non-autonomous increase of clonal patch size in PTEN wild-type cancer cells. Thus, EpicMIBI facilitates in situ interrogation of cell-intrinsic and cell-extrinsic processes involved in intratumoral heterogeneity and it is posed to help reveal principles and mechanisms of tissue developmental processes, in both normal and malignant growth, that will thus accelerate therapeutic discoveries.

Dr. Xavier Rovira-Clavé is an instructor in the laboratory of Professor Garry Nolan in the Department of Microbiology and Immunology at Stanford University, where he develops and applies multiparameter technologies to study tissue biology in models of cancer and infectious diseases. In 2016, he received his PhD in Immunology from the University of Barcelona under the supervision of Dr. Enric Espel and Dr. Manuel Reina. He also trained for a year in cancer biology studies as a visiting PhD student in the group of Dr. Gregory Emery at the University of Montreal. He has published 12 articles, including some in leading journals such as Cancer Cell and Immunity. He holds 3 granted patents. He has received 5 competitive fellowships, including the prestigious LLS Career Development Award and the EMBO postdoctoral fellowship. His areas of research include cancer, the immune system, and infectious diseases. His technical expertise includes highly multiplexed tissue imaging (spatial proteomics), single-cell assays, molecular biology approaches, cell culture, in vitro co-culture systems, engineered tumors, murine models, genome editing, bioconjugation strategies, assay automation, and single-cell spatial data analysis. His recent research efforts have been focused in the development of imaging technologies to subcellularly locate structurally unmodified drugs at the nanometer scale, track subclonal growth in situ, and co-detect multiple biomolecular species (RNA, DNA, and protein) to enable new understanding of spatial structures at the molecular, cellular and tissue levels with the long-term goal to improve disease management.

IBEC Seminar: Manuel Valero
2023-01-11 12:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
The role of inhibition in hippocampal coding
Manuel Valero, PhD NYU Neuroscience Institute, New York University (US)
The fundamental computation a single neuron performs is to integrate incoming excitatory and inhibitory inputs to decide whether to fire an action potential and feedback its activity into the network. Investigation of this synaptic computation requires access to the neuron subthreshold dynamics, whose state-of-art methodologies have remained unaltered for decades and are unrealistic for cell assemblies and behaving animals.
Instead of intracellular recording, we propose a method to optogenetically probe the membrane polarization of the cells with short depolarizing pulses using chronically implanted µLED probes (4 shanks with 3 µLED/shank). Light-sensitive neurons responded to one or more µLEDs and the spike numbers were used as a proxy for estimating relative changes in the membrane potential dynamics. Strikingly, induced spike responses gain sharply increased several-folds inside the preferred position (place fields) of the responsive cells. These results are compatible with a tuning curve model in the CA1 pyramidal cells where excitation and inhibition display a concerted and reciprocal relationship. When optogenetic stimulation was probed on non-place cells, majority of the putative non-place cells showed place-related activity. Finally, we optically probed neurons around sharp wave-ripples (SPW-Rs), hippocampal events considered a key mechanism for memory consolidation and action planning. In the short time window of SPW-R, excitatory and inhibitory neurons increased in parallel. As expected, optogenetic probing of the CA1 networks showed that, in contrast to the large gain within place fields, responsivity of pyramidal cells showed a robust decrease during SPW-Rs.
We have developed a method for studying the subthreshold dynamics of individual cells in chronic recordings using novel high-resolution optical stimulation as a proxy for membrane polarization. These experiments disclosed a reciprocal interaction between inhibition and excitation along the place fields of CA1 and demonstrated that the same exact perturbation can bring about opposite responses during exploration and transient SPW-Rs.

IBEC Seminar (online): Sam Hall
2023-01-20 10:00 - 12:00 | Online
Presentation of Open Research Europe publishing plataform
Sam Hall, from Open Research Euorpe
Open Research Europe is the European Commission’s open access publishing platform for research stemming from Horizon 2020 and Horizon Europe funding. In this webinar Senior Content Acquisition Editor Sam Hall will show how the platform enables the rapid dissemination of results and facilitates open and constructive research discussion, and maximizes the discoverability and credit for researchers and their work. Sam will also explain the funder-pays model which means that all publication fees are met by the European Commission at no cost to the researcher or the project.

Sam Hall is a Senior Content Acquisition Editor for F1000, commissioning articles and Collections for Open Research Europe. Launched in March 2021, Open Research Europe is an open access publishing Platform for research stemming from Horizon 2020, Horizon Europe and/or Euratom funding across all subject areas. Within this broad remit, Sam focusses on the research area of Engineering and Technology, and most recently the Data Note article type. Sam has almost 10 years of experience working in publishing, and in this time has worked in contrasting companies and settings. This has included society publishers, start-ups, and international governmental organizations.
Link Teams here

IBEC Seminar: Presentation of the new Programme of ”la Caixa” Foundation on Innovation in Biomedicine and Health
2023-02-17 10:00 - 12:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Alexandre Esteban, Programme Manager at ”la Caixa” Foundation
During the event, all the details of the new Innovation programme will be presented, with which the “la Caixa” Foundation reinforces its commitment to innovation and knowledge transfer in Spain and Portugal.
This new programme will fund breakthrough technologies with high market potential.

IBEC Seminar: David Caballero
2023-04-13 15:00 - 17:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Engineering the cancer: from biomaterials to on-chip solutions
David Caballero; Research Institute on Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Portugal.
Cancer is a complex and multifaceted pathology, which is influenced by numerous factors, including the tumor microenvironment (TME). This environment is composed of various of components that interact in a tightly regulated manner, affecting cancer cell behavior and response to treatment. Building realistic models of the TME is therefore essential for improving our knowledge of cancer pathophysiology and developing more effective therapies. In recent years, there has been growing interest in using precisely-engineered biomaterials and microphysiological systems to create accurate 3D in vitro models of the TME. These models can provide a more physiologically-relevant habitat for studying fundamental aspects of cancer biology and for performing drug screening. Additionally, when combined with organ-on-a-chip technology, these models offer a high degree of biomimicry and control, allowing for a precise recreation and better understanding of key biological functions of the native TME, surpassing what traditional platforms can achieve. In this lecture, I will present our latest works utilizing biomimetic materials and on-chip systems as powerful preclinical tools for engineering realistic in vitro models of the TME to study key aspects of tumorigenesis, for drug screening/discovery purposes, and for disease diagnosis applications.

IBEC Seminar: Dr. Ubaka Ogbogu
2023-04-26 11:00 | Sala Dolors Aleu, Parc Científic de Barcelona, Barcelona, Spain
Foregrounding justice, equity and inclusion as determinants of access to precision medicine: an ethical case study of patient-derived tissue organoids.
Dr. Ubaka Ogbogu, Professor and the Associate Dean Research in the Faculty of Law from the University of Alberta, Canada.
Ubaka Ogbogu is a Professor and the Associate Dean Research in the Faculty of Law. He is also the Chair of the University of Alberta Research Ethics Board 2 and the Katz Research Fellow in Health Law and Science Policy. Dr. Ogbogu is a recipient of the Confederation of Alberta Faculty Associations Distinguished Academic Early Career Award. He holds a doctorate in law from the University of Toronto, a Master of Laws degree from the University of Alberta and undergraduate degrees in law from the University of Benin, Nigeria and the Nigerian Law School.
Ogbogu’s scholarly work is focused broadly on the ethical, legal and societal implications of novel and emerging biotechnologies and associated research. His publications have explored a diverse range of issues in this field, including the ethical and legal issues associated with stem cell research, gene and engineered cell therapies, biobanks, germline gene editing. In his talk, Prof. Obgobu will reflect about these issues and also discuss how foregrounding justice, equity and inclusion are elements that impact on access to precise medicine.
He has been invited to IBEC by Nuria Montserrat.

IBEC Seminar: Charles Baroud
2023-04-28 12:00 - 13:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Modeling immune-cancer interactions using a microfluidic 3D culture approach
Charles Baroud, Professor at Ecole Polytechnique, France
Lab head at Institut Pasteur, Paris, France
Cancer immunotherapy is emerging as a transformative approach for treating cancer patients. This approach, which has shown some remarkable successes, leverages the patient’s own immune cells to locate and attack the tumor cells. However the method suffers from large heterogeneities in outcomes between different patients, in part due to the the number, phenotype, and distribution of cytotoxic T cells (CTLs) around the tumor cells. For this reason decoding the collective behavior of CTLs, as they recognize and attack cancer cells, is a major challenge that requires advanced in vitro models. This seminar will present a microfluidic platform that enables quantitative measurements of the spatiotemporal dynamics of individual CTLs as they migrate in three-dimensional (3D) environments and attack cancer spheroids. The method provides access to the trajectories of thousands of cells around hundreds of spheroids, which in turn enables probabilistic modeling of the trajectories. Analysis of the migration and killing events allows us to dissect the different phases of interactions and to identify limiting steps for different conditions. The talk will present the microfluidics and then shift focus to different biological models, with implications for both fundamental biology and for personalized medicine.

IBEC Seminar: Raphael Voituriez
2023-05-26 11:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Cellular footprints : examples of emergent memory effects in cell migration.
Raphael Voituriez, Laboratoire Jean Perrin / Laboratoire de Physique Théorique de la Matière Condensée CNRS / Sorbonne Université

Living cells actively migrate in their environment to perform key biological functions—from unicellular organisms looking for food to single cells such as fibroblasts, leukocytes or cancer cells that can shape, patrol or invade tissues. Cell migration results from complex intracellular processes that enable cell self-propulsion, and has been shown to also integrate various chemical or physical extracellular signals. While it is established that cells can modify their environment by depositing biochemical signals or mechanically remodelling the extracellular matrix, the impact of such self-induced environmental perturbations on cell trajectories at various scales remains broadly unexplored. I will discuss examples where such interactions with the environment can have deep consequences on the large scale cell dynamics, and show that they can effectively endow cells with a memory of their past trajectory.

IBEC Seminar: Anthony J. Ryan OBE
2023-05-29 12:30 - 14:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Making Science Work for Refugees and Refugees Work for Science
Prof Anthony J. Ryan, OBE, University of Sheffield, UK
At Zaatari refugee camp, 80,000 people face daily struggles that many of us cannot imagine are squeezed into six square kilometres. With highly qualified jobs at home, they are forcibly unemployed at the camp but embody values that are often forgotten by those of us in more privileged parts of the world: an adaptable approach to solving problems, an aversion to waste, a sense of community. Our research on hydroponics is focussed on the production of high-value crops close to market (urban farming) with a low carbon and water footprint using polyurethane foam as synthetic soil. I will show how a design of experiments approach can predict the productivity of crops from the reagents used in polyurethane synthesis through the properties of the foam.
We connected our work on synthetic soils with a waste disposal problem posed by UNHCR – the UN’s refugee agency. Where they saw dirty unused mattresses, we saw an alternative growth substrate. In doing so we developed small-scale hydroponics at the household and community scale. We responded to the frequent cry of the Syrian refugees – that they miss the colour green – not only did we find a technical fix, but also an impact on well-being. This benefits our work in Sheffield, we now have an urban farm built using the low-cost technology developed in Zaatari with farmers from Syria.

Professor Tony Ryan OBE is The Professor of Physical Chemistry at the University of Sheffield and the founding Director of the Grantham Centre for Sustainable Futures.
Tony’s research interests include sustainable synthesis, structure, processing, and applications of polymers using advanced analytical and measurement techniques. Recent research projects included renewable sources for polyurethane synthesis, organic photovoltaics, maximising the properties of polymers and biopolymers through flow-induced crystallisation, formulation of home and personal care products and polymer foams for high-intensity urban agriculture. He has co-authored more than 300 papers and patents and 2 books, “Polymer Processing and Structure Development” and “The Solar Revolution: One Planet, 10 Billion People, One Solution.”
More recently, Tony has been focussing on the global challenge of the food, water, and energy nexus; feeding a growing world population. Tony is very active in translational research, disseminating evidence-based science to both experts and non-experts and has been a regular contributor to TV, Radio, National Press and learned societies from The Royal Society of Chemistry to Chatham House, The Royal Institute of International Affairs. He presented evidence at the UNFCCC COP21 in Paris in 2015 and returned to COP22 in Marrakech in 2016. Tony delivered the televised Royal Institution Christmas Lectures in 2002 and was awarded an OBE in 2006 for ‘Services to Science’.
Tony holds a BSc and PhD from the University of Manchester and a DSc from UMIST. He held a NATO Research Fellowship at the University of Minnesota, was a Lecturer, Senior Lecturer and Reader in Materials Science at The University of Manchester and was seconded to the Synchrotron Radiation Source at Daresbury. In 1997 he moved to Sheffield and served as Head of Chemistry before becoming the Pro Vice Chancellor for the Faculty of Science in 2008, a role which he fulfilled until 2016.

IBEC Seminar: Danny Hatters
2023-06-06 09:30 - 11:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Protein interactions gone awry in neurodegenerative disease
Danny Hatters, Department of Biochemistry and Pharmacology | Faculty of Medicine, Dentistry and Health Sciences
The University of Melbourne, Australia

The Hatters lab studies impacts of protein misfolding and aggregation in cultured cell models of neurodegenerative diseases. We have developed approaches to examine principles governing how proteins inappropriately aggregate and new approaches with chemical reagents to monitor cysteine reactivity to probe changes in proteome foldedness and conformation. I will discuss recent findings from our laboratory that provide insight to the consequences of protein aggregation by globular proteins, and how we can model the types of protein-protein interactions that are involved. I will also discuss how we can monitor changes in protein structure and function in response to stresses and stimuli, and under conditions of disease in Huntington Disease.

IBEC Seminar: Amnon Buxboim
2023-06-19 12:30 - 13:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
How does ageing-related stiffening of brain tissue microenvironments affect the regenerative capacity of cns progenitor cells
Professor of biology and bioengineering, the Hebrew University of Jerusalem, Israel.
Ageing-related stiffening of neuronal microenvironments in the brain generates potent signals that attenuate the regenerative capacity of oligodendrocyte progenitor cells (OPCs) to proliferate and differentiate. We find that ageing drives substantial remolding of the nuclear lamina in OPCs, in which A-type lamin levels increase and B-type lamin expression decreases. Owing to the ubiquitous role of lamins in anchoring mostly heterochromatic sections at the nuclear envelope known as lamina associated domains (LAD’s), we hypothesized that ageing effects are mediated via altered genomic organization and regulation. In this study, we isolate OPCs from neonate and aged rats and study the effects of ageing-related tissue stiffening by designing and optimizing hydrogel-based matrices that mimic the extracellular elasticity and adhesion signals of neonate and aged microenvironments. Indeed, the differences in cellular morphologies and lamina compositions between neonate and aged cells are recapitulated by matrix elasticity. To characterize differences in the structural organization of the nuclear lamina, we combine high-resolution optical and electron microscopies and perform micropipette aspiration based rheology to define the viscoelastic properties of OPC nuclei within intact cells. LAD mapping is performed using optimized CUT&RUN assays that target endogenous lamin-B1, thus avoiding the effects of ectopic expression of nuclear envelope proteins, which is a prerequisite by standard methodologies. Downstream effects on transcriptional regulation are studied via single-cell RNA sequencing (scRNA-seq), thus providing insight into cell-to-cell variations. In summary, our work-in-progress highlights the mechanobiological component of ageing on progenitor cells of the CNS that can stimulate potential therapeutic strategies.

Dr. Amnon Buxboim is a professor of biology and bioengineering, the Hebrew University of Jerusalem, Israel. Trained as a biophysicist, he opened the Buxboim Lab for Mechanobiology in 2013. Dr. Buxboim research aims at understanding how physical and mechanical inputs combine with parallel signaling pathways to direct cell-fate decision-making processes. The Buxboim Lab studies oocyte maturation, preimplantation embryo development, stromal bone marrow immunomodulation, and CNS stem/progenitor cell ageing. Dr. Buxboim also studies mechanisms of nuclear mechanotransduction, as mediated via nuclear lamins and associated nuclear envelope proteins. The Buxboim Lab combines established assays, advanced computational tools, newly designed device-based technologies, and integrates single-cell level genomics with micro-rheological measurements. Based on his research findings, Dr. Buxboim develops assisted reproductive technologies to advance and improve medical care.

IBEC Seminar: Magali Suzanne
2023-06-20 11:30 - 13:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Mechanical impact of cell delamination on tissue dynamics, in developmental and tumoral contexts
Centre de Biologie Intégrative, CNRS/UMR 5088, Université Toulouse III, Toulouse, France
How mechanical forces drive morphogenesis is a fundamental question in the field of biomechanics. Combining imaging, genetics, biophysical and modeling approaches, we found that apoptotic cells, far from being eliminated passively, exert a force before dying and thus actively participate in tissue remodeling. This transient force, generated in the depth of the epithelium, constitute a mechanical signal involved in tissue folding. Comparing apoptotic cell dynamics to cells undergoing EMT, we found that a very similar apico-basal force is generated at the onset of EMT.
We further deciphered how these forces are transmitted at the tissue scale through the characterization of a specific mechanical state favoring directional force transmission and developed a new method that offers the opportunity to extract automatically, in strongly deformed epithelia, a precise characterization of the spatial organization of a given cytoskeletal network combined to morphological quantifications in highly remodeled 3D epithelial tissues.
In parallel, we turned to cancer mechanics, focusing particularly in tumor progression. Cancer is a largely widespread pathology that corresponds to an overproliferation of cells that could finally invade others tissues. Tumors develop through three increasingly aggressive steps: (1) hyperplasia, which corresponds to cells overproliferation; (2) dysplasia, during which cells can acquire a more mesenchymal phenotype, and finally (3) metastasis. Tumor development can be influenced by mutations but also by external factors, such as extracellular matrix rigidity. However, a comprehensive understanding of the intrinsic factors driving tumor evolution is still lacking. Our recent unpublished work identifies unexpected factors that could influence tumor development, and more specifically the hyperplasia/dysplasia transition, a critical step in tumor aggressiveness. This work highlights puzzling differences between developmental and tumoral mechanics.

IBEC Seminar: Dr. Benjami Oller-Salvia
2023-06-28 12:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Development of chemical and synthetic biology tools to generate biotherapeutics and to tackle brain diseases
Dr. Benjami Oller-Salvia, IQS
In our group we develop chemical and synthetic biology tools to generate biotherapeutics and to tackle brain diseases. In the first part of the talk, I will report our efforts toward developing strategies to construct conditionally-active biotherapeutics that target antigens considered undruggable. In the second part of the talk, I will present our work on peptides for drug delivery across the blood brain barrier. There, I will highlight the recent development of a new family of bicyclic brain shuttles and provide a hint toward new ways of exploring brain transport. .

IBEC Seminar: Theodore Alexandrov
2023-07-05 10:00 - 11:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Spatial single-cell metabolomics reveals metabolic cell states
EMBL
Recent discoveries put metabolism into the spotlight. Metabolism not only fuels cells but also plays key roles in health and disease. In parallel, emerging single-cell technologies opened a new world of cell types and states previously hidden beneath population averages. Yet, methods for discovering links between metabolism, cell states, metabolic plasticity and reprogramming on the single-cell level and in situ are crucially lacking. Our research aims to contribute bridging this gap. First, we will present how the emerging technology of imaging mass spectrometry can be used for the spatial profiling of metabolites, lipids, and drugs in tissues. These efforts are enabled by our big data community cloud platform METASPACE which is increasingly used across the world. Next, we will present method SpaceM for spatial single-cell metabolomics. SpaceM detects 100+ metabolites or 500+ lipids from thousands of individual cells together with fluorescence and morpho-spatial features. We used SpaceM to characterize how stimulating human hepatocytes with fatty acids led to the emergence of two co-existing subpopulations outlined by distinct cellular metabolic states. Inducing inflammation with the cytokine IL-17A perturbs the balance of these states in a process dependent on NF-κB signalling. We will show how a high-throughput version of the SpaceM method helps discover and characterize metabolic states of activated CD4+ T cells from peripheral human blood. Finally, we will present how spatial multi-omics can reveal the relationships between cell types and cell states in tissues. Overall, such methods can open novel avenues for understanding metabolism in tissues and cell cultures on the single-cell level.

IBEC Seminar: Loris Rizzello
2023-07-12 12:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Towards an evolutionary-driven universal therapy against (intracellular) pathogens
Università degli Studi di Milano
We are living a time where we believe antibiotics are the cornerstone of any infectious disease-based therapy. It is definitely out of question that antibiotics saved millions of people worldwide in the last century, and that they are still doing it very efficiently. Nevertheless, their extensive abuse, especially for zoonic applications, contributed to the rise of antibiotic resistance (AMR). AMR is one of the biggest threats in the current human history because it is estimated that the majority of the antibiotics, currently used in the clinics, will be completely ineffective for the eradication of infectious disease. This has been defined as “The New Dark Ages of Antibiotics”, which is expected to start in the next decades if no actions will be taken now. There are several causes behind AMR, but one of the most relevant is the exposure of bacteria to sub-lethal doses of the antimicrobials. One of the big aim of our research efforts is to design of a new generation of therapy that counteract this issue. It is inspired on solutions already provided by Nature, and it is based on the strategy exploited by a specific class of viruses that infect and kill bacteria only, called as bacteriophages, which are completely safe and unharmful to humans. The development of a new therapy possessing the requirements to avoid the rise in AMR represents a new legacy for the future generation in terms of anitibacterial therapies, exaclty in the same way antibiotics changed the human history in the 20th century.

IBEC Seminar: Zev Gartner
2023-07-12 15:00 - 17:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Building tissues to understand how tissues build themselves
Zev Gartner, UCSF
Cells assemble into tissues and organs through an active process termed self-organization. Harnessing tissue self-organization will ultimately advance applications as diverse as disease modeling and regenerative medicine, while revealing new strategies for fighting disease. However, progress towards these applications is limited by our incomplete understanding of how the properties of tissues emerge from their cellular building blocks. I will discuss two recent projects that aim to address this knowledge gap. In a first project, we use human mammary organoids to make the remarkable observation that tissues can behave as dynamic structural ensembles. We model the ensemble using a maximum entropy framework, and demonstrate the probability distribution of tissue structures is a function of the entropy associated with cell arrangements, the energy associated with cell interfaces, and mechanical fluctuations associated with cell motility. We map these parameters back to measurable molecular and mechanical properties of cells and their microenvironment, allowing us to engineer the structural ensemble quantitatively and systematically. In a second project we use the morphogenesis of mouse intestinal villi to reveal that tuning the geometry and active mechanics of the epithelial/mesenchymal interface is sufficient to sculpt a diversity of tissue forms. In the gut, MMP and Myosin-II dependent fluidization of a contractile and adhesive sub-epithelial mesenchyme results in a dynamic monolayer of cells with a high surface tension. Minimization of surface energy results in a process we call “mesenchymal de-wetting,” which results in the formation of an array of multicellular condensates that act to pattern and fold the overlying epithelium. Manipulating the properties of the cells or the interface results in predictable changes to the pattern and shape of the folds. These studies have some important implications for tissue engineering, disease progression, and our understanding of tissue self-organization in other contexts.

IBEC-IFIBYNE Webinar Cycle (online) 12th July 2023 at 16:00 Javier Ramon
2023-07-12 16:00 - 17:00
Organ on a chip models to emulate multi systemic metabolic diseases
Javier Ramon, IBEC
Existing on-chip tissue models typically represent a single organ, limiting systemic drug investigations. Microscale tissue analog systems aim to improve drug and toxicity predictions across various organs. However, multi-organ devices are limited, and none have explored skeletal muscle and pancreatic islets. We developed a novel multi-organ-on-a-chip platform for real-time, sensitive monitoring of cross-talk between two organs. Unlike previous electrochemical platforms, our sensing system offers cost-effectiveness, label-free detection, easy integration, multiplexing, and real-time monitoring. This platform quantifies secreted proteins with high sensitivity, crucial for understanding the relationship between skeletal muscle and the pancreas. Our work shows promise for disease modeling, drug screening, and personalized medicine.

Doctor Javier Ramon is an ICREA Professor since 2021 and the leader of the Biosensors for Bioengineering group at the Institute of Bioengineering of Catalonia. Javier studied Chemistry at the University of Catalonia and completed his PhD at the CSIC in the Institute of Advanced Chemistry of Catalonia. He conducted his postdoctoral research in Japan at the Advanced Institute of Materials and returned to Spain in 2016 as a Ramon y Cajal researcher. His research is focused on tissue engineering, biomaterials, biosensors, and integrating these technologies into organ-on-chip devices to study diseases and drug screening.

IBEC Seminar: Dan Vigneron
2023-07-18 10:00 - 11:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Translation and Initial Patient and Volunteer Studies with Hyperpolarized Carbon-13 MR Molecular Imaging
Dan Vigneron, Department of Radiology & Biomedical Imaging, University of California San Francisco
“Hyperpolarized (HP) carbon-13 MRI is an emerging molecular imaging method to monitor enzymatic conversions through key, previously-inaccessible biochemical pathways. Over 1000 human HP carbon-13 MR studies to date have shown outstanding research and potential clinical value. Just as MRI has shown value for medical imaging providing information beyond CT/X-ray, HP C-13 MRI can provide new isotope imaging biomarker information in addition to what PET & SPECT do. HP C13 MRI is safe, ~2min, non-radioactive addition to standard-of-care MRI exams, at costs less than separate PET exam. At the UCSF Hyperpolarized MRI Technology Resource Center, we are developing new techniques for rapid dynamic acquisitions to measure HP conversion rates for [1-13C]pyruvate to [1-13C]lactate, [1-13C]alanine and 13C-bicarbonate in the abdomen, pelvis, heart and brain to monitor cellular metabolism in normal tissues and pathologies. We are conducting over 15 clinical trials of HP C-13 MRI and have translated 4 different HP probes into first human studies: [1-13C]pyruvate, [2-13C]pyruvate, [1-13C]alpha-ketoglutarate, and 13C-urea. Initial results demonstrate the ability to detect cancer aggressiveness, response to therapy, cardiac disease and brain bioenergetics.

Dr. Daniel B. Vigneron Ph.D. is a Professor in the Department of Radiology & Biomedical Imaging and at the University of California, San Francisco. He also has joint appointments in the Departments of Bioengineering & Therapeutic Sciences and Neurological Surgery at UCSF and is a member of the UCB/UCSF Bioengineering graduate group. He directs the UCSF Human Imaging Core and the Advanced Imaging Technologies Resource Group that facilitates imaging technique development in the Department of Radiology & Biomedical Imaging including: Hyperpolarized Carbon-13, PET-MR, and 7T MR. He also is the Director of the NIH NIBIB-funded Hyperpolarized C-13 MRI Technology Resource Center at UCSF that was recently renewed till 2027 with 20 external collaborative and service projects. This UCSF Hyperpolarized MRI Technology Resource Center also sponsors numerous training and education opportunities including symposia/workshops focused on the development and dissemination of new HP-MRI techniques. Dr. Vigneron was elected Fellow of the International Society of Magnetic Resonance in Medicine in 2009 and to the College of Fellows of the American Institute for Medical and Biological Engineering in 2007. He received the Academy of Radiology Research Distinguished Investigator Award in 2013 and with colleagues was awarded the Gold Medal of the World Molecular Imaging Society in 2014.
Dr. Vigneron obtained his BA in Chemistry from Wesleyan University in Middletown, Connecticut in 1983, and he completed his PhD research in Pharmaceutical Chemistry from UCSF in 1988 and then conducted post-doctoral research at the Fox Chase Cancer Center in Philadelphia and at UCSF developing new MRI techniques for characterizing disease and therapy response. Prof. Vigneron’s research is focused on the development of metabolic MRI techniques for research and clinical assessments of human diseases. This research has been reported in over 350 total publications resulting in over 39,000 citations with an h-index of 109 and an i10-index of 339 and has been funded by 25 NIH grant awards including as PI: 3 P41, 1 P01 2 U01, 18 R01 and 1 S10 grant awards. Also, he has served as the Primary Mentor on 6 NIH career mentored awards. Dr. Vigneron leads the technical development aspects of the hyperpolarized carbon-13 MR program at UCSF and is the Principal Investigator of seven current NIH funded projects focused on new HP metabolic MRI techniques applied to clinical research studies of prostate cancer, metastatic cancers, brain disorders and CNS tumors.
