IBEC Seminar: David Caballero
2023-04-13 15:00 - 17:00 (Europe/Madrid) | 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.

Course · Inclusive Science; attention to diversity in science education projects
2023-04-21 09:30 - 14:00 | Centro de Recursos Educativos ONCE Barcelona, Gran Vía de les Corts Catalanes, 394, Barcelona.
This course aims to promote inclusive education in scientific education activities in non-formal settings, guaranteeing access to scientific culture for all children and adolescents, regardless of their learning needs.
During the course, general guidelines and guidelines will be presented to accompany students with visual disabilities, as well as practical examples of STEAM activities. Accessibility and digital usability will also be addressed and tools will be offered to contribute to access to information for students with visual disabilities.
This course is organized by the Bioengineering Institute of Catalonia (IBEC) in collaboration with ONCE.

Registration is required here.

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.

PhD Discussions: Ainoa Tejedera and Zarina Nauryzgaliyeva
2023-04-28 10:00 - 11:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Mimicking Sarcolemmal Damage In vitro: A 3D Skeletal Muscle Model for Drug Testing in Duchenne Muscular Dystrophy
Ainoa Tejedera Villafranca, Biosensors for bioengineering group
Duchenne muscular dystrophy (DMD) is the most prevalent neuromuscular disease diagnosed in childhood. It is a progressive and wasting disease, characterized by a degeneration of skeletal and cardiac muscles caused by the lack of dystrophin protein. The absence of this structural protein leads to the fragility of the sarcolemma, and muscle fibers are damaged during their contraction. To date, there is no cure available for patients, even though there are several molecules in drug development. However, due to the well-known limitations of preclinical research, the success rate of drugs remains low. In this work, intending to accelerate drug discovery for DMD, we developed a patient-derived functional 3D model of DMD. By using a 3D-printed casting mold, we encapsulated muscle progenitor cells in a fibrin-composite matrix. This platform incorporates two flexible T-shaped pillars that serve as anchoring points and provide continuous tension to the tissue, thus allowing the orientation of the muscle fibers. The skeletal muscle tissues expressed mature myogenic markers and showed functional phenotypes as they responded to electrical pulse stimulation (EPS) by contracting. We observed that DMD muscle tissues, after continuous contractile regimes, reproduced the loss of myotube integrity that is observed in dystrophinopathies due to the sarcolemmal instability. DMD but not healthy tissues showed functional phenotypes caused by the induced sarcolemmal damage, such as tetanic fatigue. Finally, the applicability of this DMD model in evaluating therapeutic compounds was explored. Specifically, we investigate the effect of utrophin up-regulators on functional outcomes of the model, thus identifying potential candidates for the treatment of DMD. Taking all these considerations together, our results show that bioengineered 3D skeletal muscle technology has great potential to be especially valuable in the context of current and future discovery and development of drugs to treat DMD and other neuromuscular disorders.

Dissecting early nephron patterning and segmentation in kidney organoids derived from hPSCs
Zarina Nauryzgaliyeva , Pluripotency for organ regeneration Group
The formation and maturation of organs during development is a complex, yet beautifully orchestrated process. Embryonic cells have a unique capacity to self-organize within the forming tissue, where morphogenetic movements have been shown to facilitate tissue organization and subsequent organ formation. In kidney organogenesis, the mature organ arises from crucial reciprocal interactions between the ureteric bud (UB) and metanephric mesenchyme (MM), which give rise to the collecting duct and nephron, respectively. The development of mature nephrons during kidney organogenesis is a dynamic process so far studied taking advantage of in vivo models. Accumalative findings in mice have shown that the MM undergoes mesenchymal to epithelial transition (MET), giving rise to epithelial renal vesicles (RVs) that further undergo structural changes and shift towards comma shaped and s-shaped bodies (CSBs/SSBs), which eventually develop into nephron like structures. Those studies have helped identify Wnt/b-catenin and Notch signalling pathways as key players in nephron patterning and segmentation (proximal, medial, distal segments).
At the same time, tissue morphogenesis is largely a biomechanical process, resulting from constant movements of cells, changes in forms of developing segments and forces generated therein. The biomechanical dynamics occurring during RV emergence and further nephron patterning are yet to be explored in the human context in real time. If these biomechanical processes are interconnected with mechanical signals remains an open question in the field. The answer to these questions may have an important impact for understanding nephron formation, and conversely, disease-related phenotypes due to mutations in genes orchestrating RV patterning and segmentation as occurs in congenital defects of the kidney and the urinary tract (CAKUT disease).
Here, we aim to use human pluripotent stem cell (hPSCs) derived kidney organoids to gain fundamental understanding of early nephron patterning and segmentation by mapping force transmission between cells and their extracellular matrix (ECM) and evaluating their co-evolution during renal fate specification and differentiation.
hPSCs are guided towards the renal fate on compliant PDMS hydrogels with controlled rigidities (mimicking embryonic microenvironment) in a 2D culture system. PDMS hydrogels between 3 kPa (soft) and 18 kPa (rigid) are generated by adapting the compositional ratio of PDMS components and are further functionalized and decorated with fibronectin. Using this system, we have started to spatiotemporally characterise early steps of nephrogenesis by immunofluorescence and confocal analysis, time-lapse imaging, and traction force microscopy (TFM). These analyses are nowadays conducted during RV emergence prior proximal-distal RV polarization and formation of the nephron-like segments.
The current techniques will permit quantitative and qualitative observations of multicellular behaviours at key stages of 2D renal differentiation. Furthermore, this system will allow us to spatiotemporally map cell-cell and cell-ECM forces and evaluate their evolution throughout renal fate specification with the final aim to decouple mechano-related processes sustaining nephron formation from classical biochemical signalling.

This PhD Discussion session will be held at Tower I, 11th floor Baobab room, at 10:00am.

With the support of Joan Oró grant to hire research staff in training (FI 2025), 2023 FI-2 00386, funded by Generalitat de Catalunya and by the European Social Fund Plus.

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.

Before mechanobiology had a name
2023-05-05 09:00 - 18:30 | Paranimf Facultat de Medicina i Ciències de la Salut C. Casanovas, 143 Barcelona
A celebration of three decades of cell biophysics research in Barcelona

The Barcelona area is currently recognized as an important hub for the scientific field of mechanobiology, and of cell biophysics in general. This achievement is due to the work over decades of local scientists. Among them, Prof. Daniel Navajas stands out as a pioneer in the field, before it was even called mechanobiology. His work led to important scientific achievements in cell mechanics. Perhaps even more importantly, his dedicated mentorship produced a new generation of scientists who have established their own labs and are currently expanding mechanobiology in new directions.
On the occasion of Prof. Navajas’s retirement, we take the opportunity to celebrate Mechanobiology and cell biophysics, with a symposium combining talks from former trainees and invited speakers.
The symposium will honor an exciting trajectory along three decades, but will be focused on current, ongoing research. As such, it will be of interest to anyone interested in mechanobiology, with or without a relationship to the work of Prof. Navajas.
Registration here.

Workshop on scientific illustration
2023-05-06 10:30 - 12:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
On May 6th, Roser Cussó, the artist in residence at IBEC, will be offering a scientific illustration workshop designed for participants of all ages (starting from 7 years old).
This is an open session available to everyone, where you will have the chance to explore the creative process that Roser followed during her project “Laboratori de Paisatges Humans”.
During this workshop, you will learn how to take an artistic approach to scientific concepts, as well as discover various techniques and materials that can help you create your own scientific illustrations.
As there are limited spots available, make sure to sign up for this unique session on Saturday, May 6th from 10:30 am to 12:30 pm at the Baobab meeting room (Torre I, planta 11, PCB).
Feel free to come with your family and friends!
REGISTER
LABORATORI D’IL·LUSTRACIÓ CIENTÍFICA
El pròxim 6 de maig, Roser Cussó, l’artista en residència a l’IBEC, ens oferirà un taller d’il·lustració científica adaptat per a totes les edats (a partir de 7 anys).
Es tracta d’una sessió oberta a tothom a on tindràs l’oportunitat d’aprendre el procés creatiu que va seguir Roser durant el seu projecte “Laboratori de Paisatges Humans”.
Aquest taller et permetrà posar una mirada artística a conceptes científics, aprendre diferents tècniques de representació i treballar amb diversos materials que et serviran per crear la teva pròpia obra.
Amb places limitades, no et perdis l’oportunitat d’inscriure’t en aquesta sessió única el dissabte 6 de maig d’10:30 a 12:30 h a la sala Baobab (Torre I, planta 11, PCB)
Vine amb familiars i amics! T’esperem!

Research 4 Talent
2023-05-18 10:30 - 13:00 | Sala Dolors Aleu, Parc Científic de Barcelona, Barcelona, Spain
This event is open to all undergraduate and master students interested in a research career.
The day is a chance for you to talk to our researchers and ask them questions about their day-to-day work in the lab, career paths, work-life balance, mobility etc.
In 2022 IBEC signed more than 165 internship agreements for Undergraduate and Master Students with a wide range of national and international universities. If you are interested in IBEC’s ninth edition of reSEARCH4TALENT, please register now.

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.

Innovación multidisciplinar en medicina personalizada (Spanish)
2023-05-30 10:00 - 18:00 | Instituto de Salud Carlos III Salón de Actos Ernest Lluch, pabellón 13 Campus de Chamartin Calle Monforte de Lemos, 5 Madrid
30 DE MAYO DE 2023 · INSTITUTO DE SALUD CARLOS III

La jornada «Innovación multidisciplinar en medicina personalizada» es un evento organizado en el marco del Plan Complementario de Biotecnología aplicada a la Salud. Durante el evento se presentarán las principales líneas de trabajo del Plan, que abarcan temas que van desde el uso y gestión de bases de datos en medicina de precisión hasta el desarrollo de nanofármacos, así como técnicas y procesos para terapias avanzadas y dirigidas.
El objetivo de la jornada es fortalecer y estimular colaboraciones entre los diferentes actores del ecosistema de investigación traslacional en salud.
La jornada también servirá para crear sinergias con los diferentes programas y plataformas financiadas por el ISCIIII.

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.

Greening the lab: celebrating ibec's sustainable practices
2023-06-06 15:00 - 18:00 | Sala Félix Serratosa – PCB, c/ Baldiri i reixac 10-12, Barcelona, Spain, 08028, Spain
On 6th of June we will celebrate that we are the first research center in Spain to certify its laboratories as sustainable by My Green Labs.
Since the publication of the IBEC Strategy to promote sustainability in research in 2021, IBEC has been working to make the work in the labs and in the institute more sustainable.
All this work has been recently recognized by becoming the first research center in Spain to certify its laboratories as sustainable by My Green Labs.
The next 6th of June at 3pm, we will celebrate this success and share our experience and best practices.
Come and join us at the PCB!

Advanced Functional Polymers for Medicine 2023​ conference
2023-06-07 09:00 - 2023-06-09 15:00 | Auditori Antoni Caparrós, PCB, Tower D, c/Baldiri Reixac 4-8, Barcelona, Spain
The purpose of the AFPM conference series is to strengthen the interactions within the community of chemists, material engineers, physicists, biologists and clinicians in the development of Advanced Functional Polymers for Medicine.
The current status, challenges and requirements for future developments of polymers for medicine are presented by leading experts. The conference provides an outstanding opportunity to help young scientists in their career development and offers them an interdisciplinary discussion forum within an exclusive circle.
Information, programme, and registration fee here.

PhD Complementary Skills: From Lab to Clinic
2023-06-09 10:00 - 11:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
From Lab to Clinic: An Overview of IBEC’s Clinical Mentoring Programme
Do you know what IBEC’s Clinical Mentoring Programme is about? Have you considered participating in it?
In this Complementary Skills session, Anna Gassol and Georgina Sorrosal from Col·legi official de Metges (COMB) together with Cristina Arimany from the Strategic Initiatives department at IBEC will explain the basis of the program. Meritxell Serra Casablancas (Smart Nano-Bio-Devices Group) and Luisa Camerin (Nanoprobes and Nanoswitches Group) will share their experience as the first mentees participating in the programme.
This will also be a great opportunity to learn how the programme can help in the clinical translation of the work done at IBEC and answer any questions you may have about it.

BIST Open Seminar: Roberta Croce
2023-06-12 12:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Natural Strategies for Solar Light Harvesting
Professor of Biophysics, Photosynthesis and Energy at Department of Physics of the Vrije Universiteit in Amsterdam.
In this presentation I will introduce the fundamental processes of light harvesting in photosynthetic organisms and discuss their remarkable abilities to adapt and acclimate to diverse light conditions. Photosynthetic organisms have evolved sophisticated strategies to capture and utilize solar energy efficiently, allowing them to thrive in various environments. This presentation will delve into the mechanisms by which these organisms optimize their light-harvesting capabilities, including pigment choice, photoprotection, and dynamic responses to changes in light quality and quantity.
The presentation will discuss key aspects of light harvesting, such as the spectral tuning of pigments to match available light wavelengths and the regulation of energy flow to prevent damage caused by excess light. Additionally, the remarkable acclimation abilities of photosynthetic organisms to gradual changes in light intensity will be explored, highlighting their capacity to fine-tune their photosynthetic machinery for optimal performance under varying light conditions.
By examining the natural strategies employed by photosynthetic organisms, this presentation aims to provide insights into the principles of solar light harvesting. Understanding these natural strategies offers valuable lessons for optimizing light-harvesting systems and harnessing solar energy in a sustainable and efficient manner.

Roberta Croce studied chemistry at the University of Padova and completed her Ph.D. in Plant Biology/Biophysics at the University of Milano in 1998. After two postdoc periods in Germany (MPI Mulheim a.d. Rurh) and Italy (University of Verona), she got a permanent position at the Institute of Biophysics of the CNR. In 2006 she moved to the University of Groningen where she became associate professor in 2008. Since 2011 she is Professor of Biophysics, Photosynthesis and Energy at Department of Physics of the Vrije Universiteit in Amsterdam. Her research focuses on the molecular mechanisms of photosynthesis, using an integrated approach including molecular biology, biochemistry and ultrafast spectroscopy. She published more than 180 scientific articles on the topic of photosynthesis. She is an elected member of the Royal Netherlands Academy of Arts and Sciences (KNAW) and the Royal Holland Society of Science and Humanity (KHMW). She is also a member of the Board of Reviewing Editors of Science and the Plant Cell, and the recipient of several personal research grants. In 2022 she was elected president of the International Society of Photosynthesis.

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.

PhD Thesis Defence: Nimesh Ramesh Chahare
2023-06-20 15:00 - 17:00 | acultat de Matemàtiques i Estadística-Sala d’Actes FME, Edifici U, Campus Sud
Mechanics of Epithelial tissue subjected to controlled pressure

Author: Nimesh Ramesh Chahare, Integrative Cell and Tissue Dynamics group

Biography:
Nimesh Ramesh Chahare earned his bachelor’s degree in Mechanical Engineering from the National Institute of Technology, Nagpur in 2014. He further pursued a master’s degree at the Indian Institute of Science, Bengaluru, completing it in 2016. In 2017, he began his doctoral work in Barcelona, under the guidance of Prof. Marino Arroyo at Universitat Politècnica de Catalunya, and Prof. Xavier Trepat at the Institute of Bioengineering of Catalonia. Currently, he is a PhD candidate in applied mathematics, specializing in the study of the mechanics of epithelial tissue under controlled pressure.
Abstract:
Epithelial sheets form specialized 3D structures suited to their physiological roles, such as branched alveoli in the lungs, tubes in the kidney, and villi in the intestine. To generate and maintain these structures, epithelia must undergo complex 3D deformations across length and time scales. How epithelial shape arises from active stresses, viscoelasticity, and luminal pressure remains poorly understood. To address this question, we developed a microfluidic chip and a computational framework to engineer 3D epithelial tissues with controlled shape and pressure. In the setup, an epithelial monolayer is grown on a porous surface with circular low adhesion zones. On applying hydrostatic pressure, the monolayer delaminates into a spherical cap from the circular zone. This simple shape allows us to calculate epithelial tension using Laplace’s law. Through this approach, we subject the monolayer to a range of lumen pressures at different rates and hence probe the relation between strain and tension in different regimes while computationally tracking actin dynamics and their mechanical effect at the tissue scale. Slow pressure changes relative to the actin dynamics allow the tissue to accommodate large strain variations. However, under sudden pressure reductions, the tissue develops buckling patterns and folds with different degrees of symmetry-breaking to store excess tissue area. These insights allow us to pattern epithelial folds through rationally directed buckling. Our study establishes a new approach for engineering epithelial morphogenetic events.

Reading date: 20/06/2023
Reading time: 15:00
Reading place: Facultat de Matemàtiques i Estadística-Sala d’Actes FME, Edifici U, Campus Sud
Thesis director: ARROYO BALAGUER, MARINO and TREPAT GUIXER, XAVIER
Committee:
PRESIDENT: TRIVEDI, VIKAS
SECRETARI: MUÑOZ ROMERO, JOSE JAVIER
VOCAL: SUZANNE, MAGALI

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. .

PhD Discussion: Isabela Fortunato y Marina Martinez
2023-06-30 10:00 - 11:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Cell migration up and down fibronectin gradients
Isabela Fortunato, Integrative cell and tissue dynamics group
The ability of cells to perform directed migration is essential for biological processes, such as tissue morphogenesis, immune function, and cancer invasion. Directed cell migration is often triggered by spatial gradients in the cellular environment (e.g., chemical gradients, called chemotaxis, substrate stiffness gradients, called durotaxis, or substrate-bound ligand gradients, called haptotaxis). Haptotaxis has been described in vivo as an important phenomenon during physiological and pathological conditions. However, the molecular and mechanical processes that drive this form of directed cell migration remain elusive. Moreover, generating accurate and reliable gradients of immobilized protein in vitro has been challenging and makes it harder to study haptotaxis. Here, we explore how cells sense and respond to gradients of immobilized proteins. We used a photopatterning technique to create well-controlled fibronectin gradients and we studied the migration of single mammary epithelial cells (MCF-10A). This approach allowed us to map cell migration velocity, traction forces, and actin cytoskeleton dynamics as a function of fibronectin density. We observed that cells respond to fibronectin gradients by an initial polarization towards higher protein density in the first hours of migration. Surprisingly, after the initial polarization, cells maintained their directionality even if they were submitted to a negative protein gradient. This suggests that cells adapt their polarity features to maintain the preexisting structures and organelles geometry towards low fibronectin regions until a limitation on creating new adhesions. In this work we find that one key adaptation mechanism is driven by the actin flows, specifically the increase in actin polymerization velocity at the leading edge. Besides haptotaxis, we foresee that these results will shed light on other forms of directed cell migration in which cells integrate several internal and external cues to orient themselves in physiological and pathological processes.

Living myocardial slices as a representative in vitro platform for translational cardiovascular disease
Marina Martínez, Biomaterials for Regenerative Therapies group
Cardiovascular diseases are the leading cause of global mortality, accounting for nearly 45% of all deaths in Europe. Myocardial infarction (MI) is a prevalent condition, where a region of the cardiac muscle undergoes ischemia and up to one billion cardiomyocytes die in just a few hours. The heart has a limited regenerative ability; consequently, cardiomyocytes lost due to MI cannot be replaced. In this scenario, researchers have investigated and developed alternative therapies to promote cardiac repair and regeneration.
Lactate, an important metabolite during cardiogenesis and cardiac development, has been recently described as a potential modulator of the phenotype of cardiac cells in vitro. These findings support a novel use of lactate for endogenous heart regeneration strategies. Nevertheless, effectiveness of ongoing therapeutic approaches is dependent on the level of maturation of cardiac tissue. Hitherto, the regenerative capabilities of lactate in mature cardiac tissue have not been described. In this work, we used living myocardial slices (LMS) as a model of mature cardiac tissue. LMS are 300 μm-thick slices of living myocardium with conserved physiological structure and function. Human and rat adult LMS were treated with lactate to evaluate early cellular, molecular, and functionality changes related to myocardial reprogramming, cardiac structural rearrangements, and fibrosis. Moreover, the effect of lactate was characterized in both healthy and injured adult myocardium.
Functionally, (8 mM) lactate-treated healthy and pathological human LMS displayed an increase in contractility. Expression of fibrotic, pluripotency transcription factors, and cardiomyocyte markers were detected. Exposure of healthy rat LMS to higher concentrations of lactate (20 mM) did not affect LMS viability nor altered LMS contractile force, while promoted LMS stiffening. In cryoinjured rat LMS, lactate drastically increased contractility and altered tissue remodeling in the region bordering the injury.
LMS provide a representative in vitro platform for translational cardiovascular research. By using LMS, characterization of the effect of lactate in mature cardiac tissue has been achieved. Exogenous lactate enhanced cardiac function in both human and injured rat LMS. Upregulation of transcription factors and cardiomyocyte markers may suggest an effect on partial cardiomyocyte reprogramming that would counteract the effects of tissue stiffening. Altogether, this study further supports the prospective use of lactate as a bioactive signal in new endogenous cardiac regeneration strategies.
This PhD Discussion session will be held at Tower I, 11th floor Baobab room, at 10:00am.

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.

PhD Thesis Defence: Manuel López Ortiz
2023-07-14 10:00 - 15:00
Single molecule electrochemical studies of photosynthetic complexes

Author: Manuel López Ortiz, Nanoprobes and Nanoswitches group

Reading date: 14/07/2023
Reading time: 10:00
Reading place: Aula de graus Dufort de la facultat de biologia

PhD Thesis Defense: Gerardo Ceada
2023-07-14 12:00 - 14:00
Mechanics of crypt folding, tissue compartmentalization and collective cell migration in intestinal organoids

Author: Gerardo Ceada, Integrative cell and Tissue Dynamics group

Reading date: 14/07/2023
Reading time: 12:00

Reading place: Aula Magna de la Facultad de Medicina de la Universidad de Barcelona (Campus Clínic)

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.

PhD Thesis Defense: Sefora Conti
2023-07-18 15:00 - 17:00
Mechanical phenotyping of cancer stemness in colorectal cancer.

Author: Sefora Conti, Integrative cell and Tissue Dynamics group

Reading date: 18/07/2023
Reading time: 15:00

Abstract: Colorectal cancer tumors are composed of heterogeneous and plastic cell populations, including a pool of cancer stem cells that express LGR5. Whether these distinct cell populations display different mechanical properties, and how these properties might contribute to metastasis is unknown. Using CRC patient derived organoids (PDOs), we found that compared to LGR5- cells, LGR5+ cancer stem cells are stiffer, adhere better to the extracellular matrix (ECM), move slower both as single cells and clusters, display higher nuclear YAP, show a higher survival rate in response to mechanical confinement, and form larger transendothelial gaps. These differences are largely explained by the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) in the LGR5+ cells. By analyzing scRNA-seq expression patterns from a patient cohort, we show that this downregulation is a robust signature of colorectal tumors. Our results show that LGR5- cells display a mechanically dynamic phenotype suitable for dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype suitable for extravasation and metastatic growth.

Reading place: Aula Marga, Hospital Clinic

More information here.

IBEC Seminar: MDr Joanna Sierpowska
2023-07-26 12:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Awake brain surgery mapping – a way to mitigate postsurgical impairments and a door to understanding human cognition
MDr Joanna Sierpowska from the Department of Cognition, Development and Educational Psychology, Institute of Neurosciences, University of Barcelona
Brain mapping for language and cognition during awake brain surgeries helps neurosurgeons to mitigate postsurgical impairments. At the same time, it uncovers the truth about brain functional organization. While the cortical procedures are very well studied and widely implemented since the ’50 of the XX century confirming the classical models of language production, the work on mapping the white matter pathways has developed very recently. The dual pathway model for language introduces the importance of the perisylvian white matter in the processing of speech sounds and word meaning. In the present talk, I will explain if the model was successfully confirmed by intraoperative language testing. Furthermore, I will explain how we assess language function associated with the model perioperatively in a large sample of brain tumor patients.
