IBEC Seminar: Josep Puigmartí-Luis
2023-11-10 10:00 - 12:00 (Europe/Madrid) | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
What can microfluidic technologies offer during self-assembly processes?
Josep Puigmartí-Luis, Departament de Ciència dels Materials i Química Física, Institut de Química Teòrica i Computacional (invited by César Rodriguez-Emmenegger)
Self-assembly has long being used to control covalent and non-covalent interactions where molecular design has been the major driving force to achieve a desired outcome. Like in nature, a full control over self-assembly processes could lead to rationalized structure-property correlations, a long-time sought in chemistry, physics and materials science. However, the pathways followed and the mechanisms underlying the formation of supramolecular aggregates are still a major challenge for the scientific community. Accordingly, the elucidation of nucleation and growth mechanisms will be highly required to push supramolecular chemistry to the next level, where access to nature inspired functions will be accomplished. In this contribution, I will present how reaction-diffusion (RD) conditions established within microfluidic devices can be used to uncover pathway complexity as well as to trigger pathway selection. Specifically, I will show that microfluidic RD conditions provide an unprecedented kinetic control over self-assembly processes; for example, enabling the isolation of well-defined kinetically trapped states as well as unprecedented metastable intermediates. This research provides a new tool to study and understand supramolecular chemistry, and opens up new avenues for the engineering of advanced functional assemblies and systems.

Prof. Dr. Josep Puigmartí-Luis is a chemist who completed a master in Chemistry and Food Engineering at “Institut Químico de Serrià (IQS)” (2003) and did a PhD in materials science at Institut de Ciència de Materials de Barcelona (ICMAB). His work in supramolecular and flow chemistry, has been awarded with “Premi Antoni de Martí i Franquès de Ciències Químiques”, award from the Institut d’Estudis Catalans (2009), St. Jordi award from the Institut d’Estudis Catalans and the Societat Catalana de Química (2006) and an ETH fellowship in 2008.
In 2012, he was appointed a Ramon Y Cajal (RyC) researcher, but after two years as a RyC, he decided to move back to Switzerland where in 2015 was awarded an ERC starting grant to study and control self-assembly processes of metal-organic based crystalline materials. In 2019, he was appointed as an ICREA professor and since August 2020 his group is located at the University of Barcelona (UB).

IBEC Seminar: Martí Duocastella
2023-11-15 12:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Toward the next generation of 3D optical microscopes: faster, deeper, and label-free
Martí Duocastella, Departament de Fisica Aplicada, Universitat de Barcelona
Three-dimensional (3D) optical microscopy is the tool of choice for characterizing the structure and dynamics of biological systems at sub-cellular resolution. However, most microscope architectures are tailored to capture two-dimensional (2D) information from moderately thin samples labeled with fluorophores. Due to constraints posed by light scattering and the requirement for mechanical focus translation, existing systems provide shallow penetration depth and low volumetric imaging speed, thus falling short of unraveling biological complexity inside medium-sized organisms or even organoids. In this talk, I will discuss our efforts to overcome these issues and achieve sub-millisecond imaging at potentially millimeter depths and without labels. Our strategy consists of focusing, modulating, and guiding light by exploiting the acousto-optic effect, that is, ultrasound-induced refractive index gradients. The unique interaction between ultrasound and light enables rapid 3D light control, making it suitable for the development of inertia-free light sheet microscopes that lack mechanically moving parts and offer imaging rates of tens of volumes per second. It also facilitates illumination encoding in single-pixel cameras, enabling scanless 2D imaging at 5 kHz. Interestingly, applying ultrasonic waves in a scattering medium acts as an instantaneous waveguide embedded in the medium, helping to redirect light toward a 7-fold deeper focus. I will discuss the advantages and pitfalls of these acousto-optic technologies and illustrate them with applications, including imaging of spheroids and flowing samples.

Martí Duocastella is a Serra Hunter full professor in the Department of Applied Physics at Universitat de Barcelona (UB) and leader of the Dynamic Optical Systems Lab. He completed his PhD in Physics at UB in 2010 and then moved to Princeton University as a postdoctoral research associate, where he also became the vice-president of Research and Development of the startup company TAG Optics. In 2014 he joined Istituto Italiano di Tecnologia as a researcher (group leader), until returning to Barcelona as a faculty member in 2019. His research focuses on novel optical methods for three-dimensional (3D) light engineering, with applications in materials science, sensing, and biology. He is an ERC Consolidator Grant awardee.
In 2012, he was appointed a Ramon Y Cajal (RyC) researcher, but after two years as a RyC, he decided to move back to Switzerland where in 2015 was awarded an ERC starting grant to study and control self-assembly processes of metal-organic based crystalline materials. In 2019, he was appointed as an ICREA professor and since August 2020 his group is located at the University of Barcelona (UB)

IBEC Seminar: Dr. Neil Lin
2023-12-01 12:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Epithelial Cell Variability is Governed by Physics Principles and Has Mechanobiology Impacts
Dr. Neil Lin, Assistant Professor of Mechanical Engineering and Bioengineering at University of California, Los Angeles (UCLA).
Biological systems inherently exhibit variability, seen in diverse cell shapes, sizes, and mechanical properties. Despite its prevalence, our understanding of the role of phenotypic heterogeneity in cell biology is incomplete. This talk explores how basic physics governs cell-to-cell variability in epithelial monolayers and its impact on biological processes. The first part covers how cell shape heterogeneity influences chromatin organization during crowding. The second part demonstrates that in deformed epithelial layers, nucleo-cytoskeleton coupling regulates intracellular strain distribution, influencing cellular mechanoresponse and gene expression. Overall, cell-cell variability significantly shapes tissue development and remodeling.

Dr. Neil Lin is an Assistant Professor of Mechanical Engineering and Bioengineering at University of California, Los Angeles (UCLA). He obtained his Ph.D. in physics at Cornell University, studying the microscopic mechanisms that underlie the non-Newtonian suspension flow property. From there, he went on to do a postdoctoral fellowship at Harvard University, studying approaches to recreate microenvironment cues for recapitulating kidney functions in vitro. He joined UCLA in 2019, and his research is to utilize mechanobiology principles to engineer epithelial tissues. His honors include an NIH MIRA, Prostate Cancer Foundation Young Investigator Award, and BMES CMBE Rising Star Award.

IBEC Seminar: Pavan Kumar Bosukonda
2023-12-15 14:00 - 15:00 | Sala Olivera, Tower I, Floor 11
Smart artificial microcompartments: motility and communication
Pavan Kumar Bosukonda, Assistant Professor at the Department of Chemistry, Indian Institute of Technology Roorkee

Nature is a continuous source of inspiration for the design of smart and intelligent materials. In particular, cells which are the building blocks of life display a complex symphony of various chemical/physical processes which make “life” possible and give it the characteristics which enable life to flourish and sustain. The topology of control systems in place within living cells offer many lessons in design of smart artificial microcompartments or microbots. In this talk, I will be discussing examples of microcompartments which are capable of smart adaptive motility, self-assembly and chemical-mediated communication with each other. We use simple buoyancy forces to regulate movement of our microcapsules and use antagonistic control to design relatively complex autonomous behavior by employing stratified chemical environments. The motile microcapsules can turn on/off chemical reactions and carry out logistics of molecular cargo. Also, I will discuss how we can use the combination of a stimuli responsive hydrogel and stratified environments to design a chemo-mechanical oscillator. Another focus will be our results on multiphase coacervates and how they formulate a pathway for self-assembly of microdroplets into clusters or tissue-like structures and trigger chemical communication between them.

Brief Bio: Dr. Pavan Kumar Bosukonda is an Assistant Professor at the Department of Chemistry, Indian Institute of Technology Roorkee. He carried out his doctoral studies at Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore, in the field of porous materials wherein his specific interest was to use supramolecular strategies for pore engineering in mesoporous silica. After completing his Ph.D. in 2015, he moved to the University of Bristol, UK, to work with Prof. Stephen Mann as a Marie-Sklodowska-Curie Postdoctoral Fellow in the field of protocells. His current research interests are focused on developing strategies to fabricate motile microcompartments, study of multiphase dynamics in liquid-liquid phase separation and designing strategies for regulating chemical communication between microcompartments.

IBEC Seminar: Prof. Aitor Aguirre
2023-12-19 10:00 - 11:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Reverse engineering human heart development with pluripotent stem cells
Prof. Aitor Aguirre, Institute for Quantitative Health Science and Engineering (IQ) and the Department of Biomedical Engineering at Michigan State University
During development, an exquisitely orchestrated series of biological processes lay down the map for the entirety of our bodies and carry it out to perfection. However, occasional errors occur (due to mutations, environmental factors, and other causes) and lead to congenital defects, the most common birth defect in humans affecting 1% of all newborns. Certain conditions such as obesity, diabetes, infections or drug use can increase this risk much further.
To tackle CHDs, we are reverse engineering human heart development on a dish with the use of pluripotent stem cells, creating heart organoids or synthetic mini-hearts. By recapitulating aspects of heart development in vitro, under fully controlled conditions, we can dissect gene networks and morphological changes that give rise to specific parts of the heart to understand and prevent CHD, such as single ventricle defects. Furthermore, we can also use these mini-hearts as models to study the exposure to environmental conditions and other factors that are very poorly known.

Dr. Aguirre obtained his B.S. in Biology and M.S. in Biochemistry and Molecular Biology at the University of the Basque Country and his Ph.D. in Material Science at the Institute for Bioengineering of Catalonia (IBEC). For his postdoctoral training Dr. Aguirre joined The Salk Institute under the supervision of J.C. Izpisua-Belmonte, where he explored in vivo reprogramming applied to cardiac regeneration, making significant contributions to non-coding RNA biology in human cardiac development (Cell Stem Cell, 2014; Circulation, 2015). Dr. Aguirre became Assistant Professor of Medicine at the University of California, San Diego in 2017 and joined the Institute for Quantitative Health Science and Engineering (IQ) and the Department of Biomedical Engineering at Michigan State University one year later. He became associate professor in 2023 and is currently the Chief of IQ’s Developmental and Stem Cell Biology Division and the Director of MSU’s Stem Cell Core Facility. Dr. Aguirre has extensive experience in cardiac development, cardiovascular disease, tissue engineering and -omic approaches. Dr. Aguirre has received numerous awards and nominations including the Hispanic Center of Excellence award at the University of California, a career development NHLBI K01 award and frequently serves in grant review panels for the NIH and European Commission, among others.

IBEC Seminar: Al Jord
2024-01-19 10:00 - 11:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Mechanisms of Organelle Remodeling for Cellular Function
Al Jord, Group leader of Mechanisc of organelle remodeling group, Centre for Genomic Regulation, Barcelona
To function, organisms rely on vital organs which, in turn, rely on specialized cells. At the subcellular scale, cell specialization is notably driven by robust mechanisms of organelle remodeling. Thus, discovering these mechanisms is key for the fundamental understanding of organisms in health and disease, as well as for improved organ engineering. In this seminar, I will discuss my research on organelle remodeling in somatic and female germ cells. I will first show how multiciliated cells – critical for nervous, respiratory and reproductive organs – repurpose conserved mechanisms of cell division to remodel organelles for motile ciliogenesis. I will then talk about how oocytes deploy a biophysical mechanism, based on cytoplasmic force tuning, to mechanically remodel nuclear RNA-processing organelles for reproductive success. I will conclude with some future research plans, blending my past and present interests into an interdisciplinary project that will venture into unexplored grounds of nuclear organelle mechano-regulation in somatic cells to deepen our understanding of organ development and homeostasis.

Key relevant publications :

Al Jord, A. et al. Centriole amplification by mother and daughter centrioles differs in multiciliated cells. Nature 516, 104–107 (2014).

Al Jord, A. et al. Calibrated mitotic oscillator drives motile ciliogenesis. Science 358, 803–806 (2017).

Al Jord, A. et al. Cytoplasmic forces functionally reorganize nuclear condensates in oocytes. Nat. Commun. 13:5070, 1–19 (2022).

IBEC Seminar: Marc Suarez Calvet
2024-01-31 12:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Blood biomarkers for Alzheimer’s disease: advancing diagnosis and patient care
Marc Suárez-Calvet, Barcelonabeta Brain Research Center, Fundació Pasqual Maragall, Servei de Neurologia, Hospital del Mar.

In recent years, one of the most significant breakthroughs in Alzheimer’s disease research has been the emergence of blood biomarkers that offer accurate detection of AD. Our research group has successfully demonstrated the utility of these blood biomarkers not only in patients presenting with cognitive impairement but also in individuals at the preclinical stage of Alzheimer’s. Moving forward, our focus lies in establishing the routine application of these biomarkers in clinical settings, with a keen eye on assessing their positive impact on patient outcomes. Furthermore, our ongoing efforts are dedicated to the exploration of novel blood biomarkers that can furnish valuable insights into the prognosis of Alzheimer’s patients.

IBEC Seminar: Ernesto Mejías
2024-02-21 12:00 - 13:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Vaccinia in & as next-gen oncolytic virotherapy: exploiting the synergy between oncolysis and chemotherapy
Dr Ernesto Mejías Pérez Ramón y Cajal researcher Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba. Dpto. de Biología Celular, Fisiología e Inmunología
In the fight against cancer, conventional treatments fall short of healthcare expectations. Oncolytic virotherapy is a versatile and robust alternative. With exceptional immunogenic features, Vaccinia virus (VACV) is a standout oncolytic vector whose anti-tumor ability is usually enhanced by gene deletions for better safety and heterologous genes insertions for improved cytotoxicity. Yet, VACV’s translation to effective anti-tumor treatments suffers from major shortcomings that warrant immediate solutions, among those the limited efficacy as a standalone treatment need to be overcome.
To tackle this challenge head-on, my laboratory is focused on developing next-generation synergistic therapeutic strategies towards strengthening the anti-tumor effects of the oncolytic virotherapy based on Vaccinia virus by boosting the infection efficacy and triggering a strong chemosensitization upon nucleoside analog treatment. This approach builds on the unique multifaceted role that SAMHD1 has at the interface oncolysis:chemotherapy.

IBEC Seminar: Agathe Chaigne
2024-03-08 10:00 - 11:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Molecular and mechanical regulation of abscission in stem cells
Agathe Chaigne, PhD., Group leader. Cell Biology, Neurobiology and Biophysics department, Utrecht University, The Netherlands
Abscission is the last step of cell division leading to the complete separation of the two sister cells and consists in the cutting of a cytoplasmic bridge. Abscission is mediated by the membrane remodelling machinery ESCRT which also triggers the severing of a thick bundle of microtubules that needs to be cleared prior to abscission. Here, we use mouse embryonic stem cells, which transition from slow to fast abscission during exit from naïve pluripotency to investigate the molecular mechanism for abscission dynamics. We identify a feedback loop between the activity of Aurora B, mechanics, and microtubule stability as a main regulator of abscission speed.

IBEC Seminar: Emilio Parisini
2024-03-22 12:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Engineering enzymes for biomedical and biotechnological applications
Emilio Parisini, Latvian Institute of Organic Synthesis (Riga, Latvia), University of Bologna (Italy)
Enzyme engineering has the potential to improve the activity, the stability and the substrate recognition of enzymes. As such, it paves the way for the design of novel enzymes with improved performances for a wide range of applications. This rational approach can accelerate the production and the use of biocatalysts in different biotechnological sectors, thus in turn allowing the improvement of chemical processes through the application of green chemistry concepts. In this talk, two examples from our current research will be discussed:
Fructosyl Peptide Oxidases (FPOX) are deglycating enzymes that find application as key enzymatic components in diabetes monitoring devices. Indeed, their use with blood samples can provide a measurement of the concentration of glycated hemoglobin and glycated albumin, two well-known diabetes markers. However, the FPOX currently employed in enzymatic assays cannot directly detect whole glycated proteins, making it necessary to perform a preliminary proteolytic treatment of the target protein to generate small glycated peptides that can act as viable substrates for the enzyme. This is a costly and time consuming step. The rapidly growing demand for cheap, efficient and rapid diabetes monitoring tests could be met by developing enzymatic assays for glycated hemoglobin and albumin that do not require a preliminary digestion of the proteins. In our lab, we used an in silico protein engineering approach to enhance the overall thermal stability of the enzyme and widen it active site to improve its catalytic activity toward large substrates.
The fast and uncontrolled accumulation of plastic waste in the environment has long begun to impact on the natural ecosystems and to pose an existential threat to all forms of life on our planet. Advanced technical solutions to the plastic waste management problem are therefore in urgent demand. To this end, enzymatic approaches to plastic degradation hold great promises as novel and more efficient enzymes are constantly being developed. Leaf-branch Compost Cutinase (LCC), a naturally occurring PETase, has been reported to outperform all other known PET-degrading enzymes and to present a melting temperature (Tm) of 84.7°C. This enzyme has been noticeably engineered in 2020, leading to the so-called ICCG variant (Tm = 94.0°C), the current gold standard. In our lab, we engineered a LCC that features significantly enhanced PETase activity and thermal stability relative to the gold standard ICCG.

IBEC Seminar: Kevin Braeckmans
2024-04-12 10:00 - 11:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Delivering effector molecules in cells in vitro and ex vivo by photoporation.
Kevin Braeckmans, Biophotonics Research Group, Lab. General Biochemistry and Physical Pharmacy, Ghent University, Belgium
Delivery of bioactive compounds, such as proteins and nucleic acids, into cells in vitro or ex vivo is a generic requirement for many applications in the life sciences, such as for the engineering of therapeutic cells. Physical delivery methods are attractive in this context as they are well-controlled, and can accommodate a broad variety of effector molecules and cell types. Photoporation is such a recently developed physical delivery technology which combines laser stimulation with photothermal nanoparticles. Localized thermal effects upon laser irradiation can create pores in the cell membrane, allowing the influx of external molecules in cells. Importantly, photoporation is very gentle to cells, resulting in excellent cell viability and preservation of a cell’s phenotype and functionality. In this presentation I will give an overview of the most notable work that we performed on photoporation as a next-generation transfection technology in the past decade.

Kevin Braeckmans first studied physics before doing his doctoral studies in pharmaceutical sciences at Ghent University in Belgium. From early on he was passionate about developing biophotonics technologies for drug delivery and diagnostics. In 2008 he was appointed professor at Ghent University as the group leader of the Bio-Photonics Research Group. In 2015 he received a prestigious ERC Consolidator Grant and became full professor in 2018. His research presently focuses on studying biological barriers to nanomedicines by advanced microscopy techniques, and combining light with nanoparticles to enable light-triggered drug delivery and related therapeutic applications. He is a co-author of >250 publications, Clarivate Highly Cited Author in 2022 and 2023, and co-inventor of 17 patent applications. Presently he is a co-founder and CSO/CTO of the spin-off company Trince.

IBEC Seminar: Ovijit Chaudhuri
2024-05-03 10:00 - 11:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Cell migration and morphogenesis in viscoelastic matrices
Ovijit Chaudhuri, University of Standford
The extracellular matrix (ECM) is a complex assembly of structural proteins that provides physical support and biochemical signaling to cells in tissues. Over the last two decades, studies have revealed the important role that ECM elasticity plays in regulating a variety of biological processes in cells, including stem cell differentiation and cancer progression. However, tissues and ECM are often viscoelastic, displaying stress relaxation over time in response to a deformation, and viscoplastic, exhibiting irreversible deformations in response to mechanical stress. In this talk, I will discuss our recent findings on how matrix viscoelasticity regulates various biological processes, including collective invasion by cancer cells, morphogenesis of pluripotent stem cells, and monocyte migration.

IBEC Seminar: Aurora Hernandez-Machado
2024-05-07 12:45 - 13:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Biomicrofluidic analysis of hematological diseases by means of mathematical biomechanical models and statistical analysis: Cells and hydrogels in microchannels and microrheometers
Aurora Hernandez-Machado, Departament de Fisica de la Materia Condensada, Universitat de Barcelona
We have developed microfluidic devices for precise characterization of hematological diseases. By means of one drop of blood and mathematical models based on biomechanics, we analyze the properties of cells and microrheological properties such as the viscosity of blood. We will present a microrheometer to determine in a fast, chip and sensitive way the viscosity of a drop of blood. Experimental results of malaria infected red blood cells in microchannels with endothelial slits and hydrogels with organ-on-a-chip will be discussed. Sprouting is a fundamental cellular behavior that plays an essential role in vascular development and angiogenesis. Due to its relevance to many aspects of human health, the ability to accurately reproduce cell sprouting is of broad and multidisciplinary interest. We will present microfluidic experiments and compare with theoretical models in which endothelial cells chemotactically migrate into a fibrin-based porous hydrogel which mimics the extracellular matrix. By means of statistical analysis we improve the diagnosis of the hematological diseases. We predict if a sample of blood corresponds to healthy blood or to blood with a hematological disease. We have obtained different performance for the different methods, some of them with very good results and an accuracy of 94%.

IBEC Seminar: Nicolò Accanto
2024-05-09 12:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
2P-BRAINSCOPY: pushing the boundaries of two-photon microscopy to study large neuronal networks in behaving mice.
Nicolò Accanto, Inserm researcher at the in Insitut de la Vision (IDV), in the group of Valentina Emiliani, Paris
In the past 15 years, the synergy of two-photon (2P) microscopy and optogenetics has transformed neuroscience, enabling high-resolution imaging and precise photostimulation of neuronal activity. Today, understanding how neuronal networks in the brain interact to generate perception, memory and behaviour, or in other words, deciphering the neuronal code, requires to push the limits of 2P microscopy.
This involves studying the brain of freely moving animals engaged in natural tasks and accessing thousands of neurons on a very fast (100 ms) timescale, across large (> 5 mm) brain regions, while keeping individual neuron (5 µm) spatial resolutions.

In this presentation I will outline our recent endeavours towards these goals. I will first show how 2P holographic photostimulation based on spatial light modulators is capable to precisely target individual neurons within a large volume [1]. I will then describe how we can use minimally invasive GRIN lenses to access deeper brain regions [2], below the scattering limit. Finally, I will detail our most advanced technique: a novel fiber-based miniaturized microscope to image and photostimulate neuronal activity in freely moving mice [3,4]. In the last part of the talk, I will present future directions for further developments and applications in neuroscience.

References
[1] Accanto, N. et al. Multiplexed temporally focused light shaping for high-resolution multi-cell targeting. Optica 5, 1478 (2018).
[2] Accanto, N. et al. Multiplexed temporally focused light shaping through a gradient index lens for precise in-depth optogenetic photostimulation. Sci. Rep. 9, 7603 (2019).
[3] Accanto, N. et al. A flexible two-photon fiberscope for fast activity imaging and precise optogenetic photostimulation of neurons in freely moving mice. Neuron 111, 176-189.e6 (2023).
[4] Lorca-Cámara, Antonio, Blot, Francois & Accanto, N. Recent advances in light patterned optogenetic photostimulation in freely moving mice. Neurophotonics In press, 11, S11508 (2024).

Seminar “The Canadian health research following COVID-19 pandemic – artificial intelligence (AI), generative systems, quantum computing and beyond"
2024-05-14 15:00 - 17:00 | Aula Manuel Corachan (5th floor) · UB Faculty of Medicine Clinic (Carrer de Casanova, 143, Eixample, 08036 Barcelona)
We are glad to invite you to this seminar organized by IBEC where Marek W. Radomski, Vice-Dean Research College of Medicine, University of Saskatchewan, Saskatoon, Canada will talk about the Canadian health research following COVID-19 pandemic, the next Tuesday 14th of May at 15h at the Faculty of Medicine Clinic (UB).
Marek W. Radomski,
Vice-Dean of Investigation College of Medicine, University of Saskatchwan, Saskatoon, Canada and President of The Association of Faculties of Medicine of Canada, Vice-Deans Research Committee.
He has developed his research career in Poland, the United Kingdom and Ireland (both in a pharmaceutical company and at Trinity College in Dublin), at the University of Houston and in Canada (in two universities)
The Canadian health research following COVID-19 pandemic – artificial intelligence (AI), generative systems, quantum computing and beyond.
The COVID-19 pandemic claimed millions of lives worldwide and greatly disrupted societal fabric across the globe.
Despite amazing achievements of vaccine research and development many areas of health research have been adversely affected by limitations caused by pandemic.
However, AI, generative systems and quantum computing are examples of a postpandemic research acceleration with substantial health research and service potentials.
The presentation will focus on these challenges and opportunities through the lens of the College of Medicine University of Saskatchewan and of the Association of Faculties of Medicine of Canada.

14/05/2024 · 15h

Aula Manuel Corachan (5th floor) · UB Faculty of Medicine Clinic (Carrer de Casanova, 143, Eixample, 08036 Barcelona)

IBEC

No registration needed

IBEC Seminar: Erika Ferrari
2024-05-17 10:00 - 11:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Beating Organs-on-Chip: leveraging on motion to mimic human organ physiological/diseased states in vitro
Erika Ferrari, Commercial Science Leader, BiomimX Srl
Beating Organs-on-Chip are in vitro miniaturized models developed within the uBeat® platform, which integrates microfluidics, 3D human cell culture and controlled mechanical stimulation to recapitulate,
with unprecedented precision and predictability, clinically relevant models reflective of human pathophysiology and complex diseases. Every tissue in the body is subject motion and this motion can be mimicked within the uBeat® platformplatforms, which provides 3D microtissues with controlled mechanical stimulation (e.g., stretching or compression) resulting in more reliable, responsive, and predictive in vitro model models to investigate new therapies. BiomimX lead model is uHeart Visone, Tox Sciences, 2023; +4 additional cardiac publications ), a functional beating heart on a chip for cardiotoxicity and safety testing. uHeart was recently qualified with 12 drugs as a predictor of functional cardiotoxicity, showing 83.3% sensitivity, 100% specificity, a nd 91.6% accuracy. BiomimX pipeline consists of predictive physiological and pathological models, engineered solely through mechanical stimulation, without the need for introducing exogenous compounds (e.g., cytokines) into the cell culture chamber. uKnee the first in vitro model of human osteoarthritis; Occhetta, Nature Biomed Eng, 2019 ) has successfully supported a recent IND application. Other key models include uScar cardiac fibrosis; Visone, Adv Healthcare Mat, 202 2023), uGut a barrier model of the intestinal epithelium & endothelium; Ballerini, Nature Biomed Eng, under review ), uLung and uLiver Heart a multiorgan platform used to study the off-target cardiotoxicity of liver-metabolized drugs; Ferrari, Adv Mat Tech, 2023 ).

IBEC Seminar: Sergi Garcia-Manyes
2024-05-24 10:00 - 11:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Single molecule insights into cellular mechanotransduction
Sergi Garcia-Manyes, Single Molecule Mechanobiology laboratory, The Francis Crick Institute and King’s College London

Cellular mechanostransduction relies on the conversion of mechanical cues into chemical signals, which propagate from the focal adhesion hub through the cytoskeleton to ultimately reach the nucleus through the Nuclear Pore Complex (NPC), and switch on specific force-dependent transcriptional programmes. However, how cellular mechanotransduction is regulated by the nanomechanical properties of the underpinning force-bearing proteins remains largely unknown. Here we first used a newly developed single-molecule magnetic tweezers combined with UV-light to demonstrate that oxidation of a previously cryptic methionine in the talin mechanosensor impairs vinculin binding. When translating the single-molecule findings into the cellular context, we found a loss in talin/vinculin co-localisation at focal adhesions of NIH3T3 mouse fibroblasts when exposed to µM concentrations of H2O2 and a decrease in the nuclear localisation of the YAP transcription factor (TF). In this vein, how the nuclear shuttling of mechanosensitive TFs is regulated by their mechanical properties remains also unclear. By using a combination of single-molecule mechanics and single-cell optogenetics, we discovered that proteins with locally soft regions in the vicinity of the nuclear-localization sequence exhibit higher nuclear-import rates. Inspired by these findings, we designed a short and easy-to-express unstructured peptide tag that accelerates the nuclear-import rate of stiff protein cargos. Altogether, our cross-scale experiments provide a single molecule perspective onto cellular mechanotransduction.

IBEC Seminar: Wenting Zhao
2024-05-31 10:00 - 12:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Engineering the Nanoscale Membrane Topography in Cells
Wenting Zhao, School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore and Institute for Digital Molecular Analytics and Science (IDMxS), Singapore
Abstract.
Cell membranes serve as a central platform to host a variety of proteins essential for cellular activities such as cell signaling, morphogenesis, and membrane trafficking. At the same time, the membranes also undergo drastic morphological changes in a number of essential processes, such as endocytosis, intracellular trafficking, and cytokinesis, etc. An intriguing yet challenging question to answer is whether and how the shapes of the membrane impact the dynamics of membrane proteins or the periphery proteins interacting with the membrane. However, membrane shape changes often happen at sub-micro to the nanoscale, which is approaching the limit of conventional microscopy imaging resolution and difficult to examine quantitatively. In this work, we will introduce our efforts in employing vertically aligned nanostructures to generate defined membrane topography in live cells and in vitro. We will discuss our findings on the membrane curvature-guided accumulation of membrane proteins, including oncogenic Ras proteins and viral proteins, as well as the membrane-associated protein condensation. In addition to plasma membrane, we also explore the nanoscale topography guidance on nuclear membrane and its implication in differentiating malignant cancer cells. We envision more new insights would be revealed by bridging advanced nanotechnology to nanoscale dynamics at cell surfaces.

Short Bio
Dr. Wenting Zhao is currently an assistant professor in the School of Chemistry, Chemical Engineering, and Biotechnology at Nanyang Technological University, Singapore. She received her Ph.D. degree in Bioengineering at the Hong Kong University of Science and Technology, and completed her postdoc training at Stanford University. Her research group aims to reveal the nanoscale interplay between membrane morphology and protein assembly using advance nanofabrication and nanomaterials. Specific focuses of her studies are on the nanoscale topography-guided protein clustering and complex assembly, and their impacts on disease progression, such as cancer progression, viral replication, and immune activation.
Group website: www.wtzhaolab.com.

IBEC Seminar: Irene Lázaro
2024-06-05 16:00 - 17:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Enhanced regeneration through in vivo cell reprogramming: lessons from the first decade of research and a success story in the mouse heart
Irene de Lázaro, PhD1,2,3
1 Department of Biomedical Engineering, NYU Tandon School of Engineering, New York University
2 Cardiovascular Research Center, NYU School of Medicine and NYU Langone Health
3 Harvard John A Paulson School of Engineering and Applied Sciences, Harvard University

Our lab designs and deploys bioengineering strategies – including gene therapies and nanomedicines – to reprogram cell identity, differentiation and/or cellular responses in living organisms with the ultimate goal of helping tissues regenerate better. In this seminar, I will share the lessons learned after the first decade of in vivo cellular reprogramming research. Moreover, I will present our most recent data that demonstrates that on and off expression of stemness-related transcription factors induces partial reprogramming of cardiac myocytes to a rejuvenated state. In an age-dependent mouse model of heart failure, reprogramming the biological age of cardiac myocytes to a youthful state resulted in significant improvement of cardiac function.

IBEC Seminar: Jan Lammerding
2024-06-12 10:00 - 11:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Nuclear mechanobiology – from striated muscle disease to ultrarapid cellular mechanosensing
Jan Lammerding, PhD, Weill Institute for Cell and Molecular Biology & Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA
Abstract. The nucleus is the characteristic feature of eukaryotic cells and houses the genomic information of the cell. The Lammerding laboratory is investigating how physical forces acting on the nucleus can challenge the integrity of the nucleus, alter its structure, and cause genomic, transcriptomic, and other functional changes. In this seminar, I will discuss our findings that highlight the importance of the nuclear envelope proteins lamins A/C in mediating nuclear stability and mechanotransduction in mechanically stressed cells and tissues, and how lamin mutations result in reduced nuclear stability and increased nuclear damage in striated muscle cells, which may explain the muscle-specific defects in many diseases caused by lamin mutations (laminopathies). Our data demonstrate that reducing cytoskeletal forces on the fragile lamin A/C mutant nuclei by disrupting the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex is sufficient to reduce nuclear damage in striated muscle tissue and to improve cardiac function and survival in multiple mouse models of lamin A/C related striated muscle disease. Furthermore, by combining cyclic strain application with precision nuclear run-on sequencing (PRO-seq), a novel transcriptome sequencing technique that, unlike traditional RNA sequencing, enriches for nascent RNA transcripts and simultaneously provides a base-pair resolution map of active RNA polymerases, and Omni-ATAC, an improved chromatin accessibility assay, we recently established an experimental pipeline to detect rapid, genome-wide changes in chromatin organization and transcription in response to cyclic mechanical strain. Our studies indicate that cyclic strain application results in the transcription of numerous mechanoresponsive genes within less than 2 minutes, which is faster than the expected time for typical mechanoresponsive cytoplasmic signaling pathways to reach the nucleus, and that the mechanoresponsive genes are already poised for gene transcription. These findings point to an exciting, previously unrecognized role of the nucleus in regulating the activation of mechanoresponsive genes.

IBEC Seminar: Shahid Uddin
2024-07-05 10:00 - 12:00 | IBEC, floor 11, Tower I, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Developability assessment of biologics and formulation of novel molecules
Shahid Uddin, PhD, MBA, Senior Director of Drug Product, Formulation & Stability within the CMC department at Immunocore, UK
It’s vital to ensure appropriate assessment of molecules at the early research phase is carried out to risk mitigate movement into the development phase. This ensures the best risk of success with minimal usage of resources and finances. This presentation will highlight the procedures for assessing developability and also showcases the challenges associated with administering low-concentration biologics.

IBEC Seminar: Sabina Quader
2024-07-17 15:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Nanomedicine to Tackle Unmet Medical Needs in CNS Disorders
Sabina Quader, Innovation Center of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion, Kawasaki, Kanagawa 210-0821 Japan
The brain is undoubtedly the body’s most essential and intricate organ, and brain disorders are closely tied to this intricacy. Categorized as “CNS diseases,” a wide range of brain-related conditions – including Alzheimer’s, dementia, Amyotrophic Lateral Sclerosis, stroke, brain tumors, and more – present daunting challenges. Regrettably, many of these diseases currently lack adequate treatment, underscoring the urgent need for innovative and multidimensional efforts to combat these persistent problems. In this regard, nanomedicine shows tremendous potential for diagnosing and treating many life-threatening diseases, including cardiovascular and genetic disorders, CNS diseases, and cancers1. The field of nanomedicine is constantly revolutionizing healthcare with innovative approaches to tackling severe health issues. However, it is also crucial to actively translate these novel approaches more effectively. In our laboratory at the Innovation Center of NanoMedicine (iCONM), we aim to effectively bridge innovation and translation. Our nanomedicine platform is based on polymeric micelles that are constructed from poly(ethylene glycol)-b-poly(amino acids) (PEG-PAA) copolymers and have already demonstrated significant promise through their clinical translation potential2. The PEG-PAA copolymers are highly biocompatible and have the unique ability to engineer versatile, dynamic covalent chemistry-based approaches to link the cargo with the carriers; this feature ultimately improves spatiotemporal control over drug release kinetics, which is one of the critical properties of drug-loaded nanocarriers, along with size and surface properties. In this presentation, optimal design features of nanomedicine will be discussed, focusing on treating CNS diseases, mainly brain cancers3,4. An overview of our Japan-Spain international collaborative research focused on drug delivery to hypothalamic neurons for tackling obesity will also be presented5.
References–

Quader and K. Kataoka*, Mol Ther, 25 (2017) 1501.
Cabral, K. Miyata, K. Osada, K. Kataoka*, Chem. Rev., 118 (2018) 6844.
Kinoh, S. Quader, H. Shibasaki, X. Liu, A. Maity, T. Yamasoba, H. Cabral*, K. Kataoka*,ACS Nano, 14 (2020) 10127.
Quader*, X. Liu, K. Toh, Y.-L. Su, A. R. Maity, A. Tao, W. K. D. Paraiso, Y. Mochida, H. Kinoh, H. Cabral, K. Kataoka*, Biomaterials, 267 (2021)120463.
J Garcia-Chica, WK D Paraiso, S Zagmutt, A Fosch, A Reguera, X Ariza, S Alzina, L Sanchez-Garcia, S Fukushima, K Toh, N Casals, D Serra, L Herrero, J Garcia, K Kataoka, X Ariza, S Quader*, R Rodriguez-Rodriguez*, Nanomedicine targeting brain lipid metabolism as a feasible approach for controlling the energy balance, Sci. 11 (2023) 2336-2346

Dr. Quader did her Ph.D. in Synthetic Organic Chemistry from Griffith University, Brisbane, Australia 2007. Following her Ph.D., she started working as a Research Chemist at Research Directions Pty Ltd, Brisbane, Australia. In 2010, she joined Professor Kazunori Kataoka’s world-renowned biomaterial research laboratory at the Materials Engineering Department of Tokyo University with a Japanese government -funded prestigious JSPS postdoctoral fellowship. After completing two years of JSPS fellowship, she continued her work at the same laboratory for another two years as Project Researcher. Since 2015, she has been an integral part of the Innovation Center of NanoMedicine (iCONM), Kawasaki, Japan, as a Senior Research Scientist and, as of 2023, as a Deputy Principal Research Scientist. Dr. Quader’s area of expertise lies in developing stimuli-sensitive nanomaterials tailored for targeted drug delivery to address challenging diseases. Dr. Quader is currently a principal investigator in multiple projects and overseeing international research activities at iCONM as Chief Coordinator of Global Partnership. One of her international collaborative research endeavors, “COnCorD,” was one of the three bilateral projects awarded by the Spanish State Agency for Research (AEI) and the Japanese Medical Research Agency (AMED) as a result of an invitation for joint project proposals from early-stage researchers in Japan and Spain in the “Nanomedicine” research area.

IBEC Seminar: Carlos Moreno Yruela
2024-07-19 10:00 - 11:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Semi-synthetic nucleosomes to stabilize and image enzyme-chromatin interactions
Carlos Moreno Yruela, Researcher in Chemical Biology, EPFL, Switzerland
Chromatin structure regulates gene expression and is tightly controlled by histone post-translational modifications. SIRT7 is a histone lysine deacylase found to maintain oncogenic gene expression profiles supporting tumor growth and
metastasis. Interestingly, the activity of SIRT7 is fully dependent on binding to nucleosomes within chromatin. This feature has limited the development of inhibitors and chemical probes to further dissect its role in cancer progression. Here, we develop nucleosome-based tools for structural characterization and high-throughput screening. Thanks to 2- and 3-fragment native chemical ligation methods, we introduced synthetic peptides into the structure of histone H3, to install either mechanism-based thiourea crosslinkers or fluorescence quenchers at the positions of known SIRT7 substrates. First, mechanism-based crosslinking nucleosomes allowed us to stabilize the interaction of SIRT7 with its nucleosome substrates and obtain structures by cryoEM. The different complexes revealed a multivalent and non-canonical nucleosome binding mechanism, and specific residues responsible for targeting different substrates within the nucleosome. Second, nucleosomes with acyllysine fluorescence quenchers and a neighboring fluorophore proved to be SIRT7-activated fluorogenic substrates and will be used for high-throughput screening and single-molecule biophysical characterization. All in all, we developed a strategy to stabilize enzyme-chromatin interactions for detailed structural studies, as well as a platform for the development of translatable SIRT7-targeting cancer therapeutics.

Carlos studied Chemistry at the University of Zaragoza and obtained his M.Sc. in Drug Discovery from the University of Surrey (UK). He obtained his Ph.D. in Chemical Biology from the University of Copenhagen in 2019, on the development of assays and chemical probes for histone deacetylases in the laboratory of Prof. Christian Adam Olsen. He stayed 3 more years in Copenhagen as postdoctoral fellow, working on the newly found lactyl-lysine modification of histones. In 2022, Carlos moved to EPFL Lausanne (Switzerland) thanks to a postdoctoral grant from the Independent Danish Research Council, where he uses protein semi-synthesis to generate complex in vitro systems for translatable biophysical studies and anticancer drug development. Carlos is now an independent postdoctoral fellow of the Swiss National Science Foundation.

IBEC Seminar: Prof Marcelle Machluf
2024-09-13 14:00 - 16:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Harnessing the power of stem cell therapy in an off-the-shelf nano-delivery platform for treating brain disorders
Prof Marcelle Machluf, Faculty of Biotechnology and Food Engineering, Technion, Haifa, Israel
Mesenchymal stem cells (MSCs) have gained the most attention in cell therapy, owing to their ability to traverse physiological barriers, and target different sites of inflammation including neurological deseases and primary and metastatic tumors, while exhibiting relative allogeneic safety. However, once transplanted, MSCs undergo changes that alter their targeting capabilities and increase their immunogenicity, only permitting them to exert a short hit-and-run effect. We hypothesised that overcoming these challenges can be realised by combining the safety and inflamatory targeting capabilities of MSCs in an inanimate platform that can withstand limiting host influences. The foundations for this combination are laid by a novel class of nano-vesicles (200 nm), termed nano-ghosts (NGs), equipped with the membrane proteins of MSCs and can be engineered to express additional exogenous ones. The developed -cGMP compliant- technology for the production of NGs from the whole MSC membranes, allow us to load them with a diverse payloads and/or engineer them to express ligands that can combat brain tumors and neuroinflamatory deseas such as MS. Their abundance of natural targeting mechanisms allows the NGs, injected i.v., to bypass the BBB and penetrate the entire tumor bulk or inflamatory site, and rapidly deploy their payload directly into the targeted cells leading to unprecedented tumor growth inhibition and increased animals’ survival in intracranial glioma model. Surprising data also demonstrate that the NGs by themselves can modulate inflammation via cell-cell interaction and significaly reduce MS symtomes in EAE mice without any payload, paving the way for their use in other neuroinflamatory deseas such as Alzhimer and Parkinson. Thus, our results, so far, clearly demonstrate the translational potential of NGs, both as targeted delivery platform as well as a novel immunomodulatory biologic for brain diseass.

IBEC Seminar: Maria João Amorim
2024-09-18 12:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Advances in understanding and manipulating influenza A virus liquid inclusions
Maria João Amorim, PhD, Group Leader, Cell Biology of Viral Infection Lab, Católica Biomedical Research Centre, Universidade Católica Portuguesa, and Instituto Gulbenkian de Ciência, Portugal
Many viruses form biomolecular condensates de novo as part of their replication programmes. Influenza A virus is an important human pathogen that has the genome divided into eight different RNA segments. Interestingly, each infectious particle contains no more than eight RNA segments and one of each type. Here, we show that during infection influenza forms liquid condensates named viral inclusions where the eight RNA segments accumulate. Viral inclusions are formed with a single RNA type, suggesting that these structures are formed before the genomic complex assembles and raises the hypothesis that these are specialized sites for the formation of influenza epidemic and pandemic genomic complexes. We will exchange views on why being liquid could constitute an interesting framework for understanding how influenza genomic complex forms. After, we will expose advances on how viral inclusions are formed and provide proof of the concept that condensate hardening blocks viral infection in cellula and in vivo. Since native or engineered transitions affect condensate behavior, phase transitions may offer novel antiviral opportunities for influenza, as well as for many other viruses that utilize biomolecular condensates during their lifecycle. Finally, we will show that our efforts to reconstitute in vitro influenza A virus inclusions give rise to a network of interactions built specifically during infection but, despite being dynamic, are not liquid but rather a gel-like state. We debate several hypothesis on why we have been unable for far to attain a liquid like character.

IBEC Seminar: Slav Bagriantsev
2024-11-15 10:00 - 11:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
3D architecture and mechanism of touch detection in the Pacinian corpuscle
Slav Bagriantsev, Associate Professor of Cellular & Molecular Physiology, Yale School of Medicine, USA
Pacinian corpuscles are specialized mechanoreceptor end-organs that detect transient touch and high-frequency vibration in the skin and viscera of many vertebrates. Corpuscles have a complex cellular organization, which includes a mechanoreceptor afferent surrounded by lamellar Schwann cells (LSCs) and several layers of outer core cells. How these components contribute to the sensory tuning of Pacinian corpuscles is unclear. We used Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) to determine the detailed 3D architecture of an entire Pacinian corpuscle, including all corpuscular components, and utilized electrophysiology to reveal the contribution of each component to touch detection. In the prevailing model, the multilayered outer core serves as a mechanical filter that limits static and low-frequency stimuli from reaching the afferent terminal—the presumed sole site of touch detection in corpuscles. We show that the outer core is dispensable for the sensory tuning of Pacinian corpuscles to transient touch and high-frequency vibration; instead, these properties arise from the inner core. We show that LSCs express mechanically gated ion channels and form a gap junction-coupled syncytium around the afferent terminal. By acting as additional touch sensors, LSCs potentiate mechanosensitivity of the terminal, which detects touch via fast inactivating ion channels. We present a new model, in which the functional tuning of Pacinian corpuscles is enabled by an interplay between mechanosensitive LSCs and the afferent terminal in the inner core.

IBEC Seminar: Benoît Ladoux
2024-11-19 14:30 - 16:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Mechanical imprints of cell fate and cell competition
Benoît Ladoux, Institut Jacques Monot (IJM) Paris
Epithelia are communities of cells with close intercellular communications and of highly ordered coordination in their motion.
Mechanical properties of epithelial tissues are important for our understanding of many vital biological processes, including homeostasis, morphogenesis, and metastasis and are tightly regulated by cell-cell interactions. I will present examples highlighting the importance of mechanical forces during cell extrusion and cell competition. In the first part, I will focus on how cell extrusion and the fate of extruding cells from epithelial tissues can be determined by mechanical stresses. In the second part, I will show how cell competition, a mechanism by which the expansion of one cell population leads to the elimination of another, can be governed by the transmission of intercellular forces. Throughout the talk, I’ll discuss the close links between mechanics and cell biology, as well as possible analogies between physical and biological systems.

IBEC Seminar: Raül Andero Galí
2024-11-28 12:00 - 13:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Translating fear mechanisms between humans and mice
Raül Andero Galí, PhD, ICREA Research Professor at the Institute of Neurosciences of the Autonomous University of Barcelona
Sex-specific mechanisms in fear memory and extinction may explain certain neuropsychiatric disorders like Post-Traumatic Stress Disorder (PTSD). In male mice, chemogenetic silencing of centromedial amygdala (CeM)-Tac2 fibers in the lateral posterior part of the Bed Nucleus of the Stria Terminalis (BNSTpl) impaired fear memory, while optogenetic excitation enhanced inhibitory postsynaptic currents. In vivo calcium imaging in freely moving mice revealed a sex-dimorphic fear memory engram in the BNSTpl. In humans, the TAC3R single nucleotide polymorphism (SNP) (rs2765) reduced CeM-BNST connectivity and impaired fear memory in men but not women. In a different study, female mice subjected to acute stress exhibited fear extinction impairments linked to hypothalamic Pacap and Pac1R upregulation. Similar fear extinction deficits were observed in women with PTSD carriers of the PAC1R SNP (rs2267735). Together, these studies highlight sex-differences in neural circuits regulating fear memory, which may influence vulnerability to PTSD.
Please contact Silvia Pittolo if you would like to meet the speaker: spittolo@ibecbarcelona.eu

IBEC Seminar: Prof. Yuval Ebenstein
2024-12-17 15:00 - 16:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Beyond NGS: A toolbox for single-molecule epigenetic analysis of DNA
Prof. Yuval Ebenstein, Department of Physical Chemistry, Department of Biomedical Engineering, Founder, Innovation and Entrepreneurship Center Tel Aviv University, Israel.
DNA sequencing (NGS) is revolutionizing all fields of biological research. Still, it fails to extract the full range of information associated with genetic material and cannot resolve important variations between genomes. The information content of the genome extends beyond the base sequence in the form of chemical modifications such as DNA methylation or chromosomal association with DNA-binding proteins (chromatin). For the last decade, my lab has been developing tools for genomic analysis at the single-cell and single-molecule levels. I will show how the physical extension of long DNA molecules in nanofluidic channels reveals this information in the form of a linear, optical, or electrical “barcode,” like beads threaded on a string, where each bead represents a distinct type of observable. I’ll present a biochemical and physical toolbox for mapping epigenetic modifications in the genome and demonstrate its application in clinical cancer research. Finally, I will talk about a DNA chip developed in the lab and the adventure of building a startup based on this technology.

Short Bio:
Prof. Yuval Ebenstein is a scientist and entrepreneur with years of experience in translational research. Yuval is head of the NanoBioPhotonix Lab and the founder of the Tel Aviv University Entrepreneurship Center. In his lab, Yuval combines Chemistry, Physics, Biology, and bioinformatics in order to study the human genome. His lab explores genomes utilizing tools and reagents from the realm of nano-technology, zooming in on single cells, single chromosomes, and single molecules. Yuval is the winner of two ERC awards for developing genomic technologies and is the founder of JaxBio, a liquid biopsy methylation-based diagnostics startup.

IBEC Seminar: Sylvain Gabriele
2025-01-14 14:30 - 16:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Mechanobiology of epithelial cells: curvature, confinement and memory
Sylvain Gabriele, University of Mons
The directed migration of epithelial cell collectives through coordinated movements is fundamental to numerous physiological and pathological processes. While these dynamics are often studied in large, confluent monolayers, many migration phenomena involve the movement of small, polarized epithelial clusters and their interactions with external geometries. Additionally, epithelial monolayers must adapt to variations in local curvature during processes like tissue folding and morphogenesis, which are critical for development and homeostasis. Despite their significance, spatial confinement and curvature-induced adaptations remain poorly understood due to challenges in reproducing these conditions in vitro. We will first introduce a photopolymerization technique using optical photomasks to fabricate wavy hydrogels, allowing precise exploration of how concave and convex curvatures influence the mechanical properties of epithelial monolayers and induce nuclear deformations. Our findings highlight the pivotal roles of active cellular mechanics and nuclear mechano adaptation in regulating epithelial responses to substrate curvature. In the second part, we will employ well-defined in vitro systems based on micropatterned adhesive stripes to examine the migration of individual cells and small epithelial clusters with controlled geometries. We will demonstrate the critical role of geometry in defining the migration behaviors of cells and clusters, offering a framework to uncover the rules governing their interactions with physical boundaries. Notably, we will present evidence that migrating cells retain a “mechanical memory” of past morphological states, enabling enhanced navigation through confined environments. This long-term memory of confinement, mediated by actin cortex remodeling, provides new insights into how cells adapt to dynamic microenvironments and navigate complex spaces.
Please contact Manuel Salmeron Sanchez if you would like to meet the speaker: msalmeron@ibecbarcelona.eu
