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

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

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

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

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

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

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.

IBEC Seminar: Matthias Schulze
2023-07-26 15:00 - 17:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Highlights of 20 years DNP with Merck as partner
Matthias Schulze, Merck
Introduction of Merck’s capabilities to supply specifically labeled tracers in different grades.
Describing the milestones of DNP towards establishing that method as a powerful tool in cancer diagnostics. Outlining the challenges and the scope on projects utilizing 13 C labeled reagents.

Matthias Schulze studied chemistry at the TU Berlin and gained his PhD in 1991 for research in natural product synthesis. Subsequent stays at various sites abroad (Norman, Oklahoma and Columbus, Ohio) extended his expertise in analytical and synthetical techniques. Later, he worked as a group leader at the University Bonn on mechanistic questions in metal-organic chemistry and new ways to access cyclic natural products. He has 20 years of experience in stable isotopes and its applications in a corporate environment. His current role is that of a technology manager for stable isotopes in EMEA. Ever since he worked with numerous researchers to support them in a broad range of fields, focusing on biochemical and medicinal topics

IBEC Seminar: Virgil Percec
2023-09-05 10:00 - 12:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Reprogramming the Factory of Life to Target the Delivery of mRNA via Helical Chirality
Virgil Percec, Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia
Homochiral helical self-organizations are known at the macroscopic level in nature, art, architecture and science for thousands of years [1a,b]. However, molecular helicity was discovered in proteins and DNA [2] only in the early 1950th and in molecular, macromolecular and supramolecular complex nanosystems emerged soon after [1c,d,e,f]. Our ability to program functions at the supramolecular level based on helical chirality is less advanced than the same process at the macroscopic level during Archimedes and Leonardo da Vinci times. The principles “discover-elucidate mechanism-predict programmed primary structure” elaborated in our laboratory and aided by synthetic methodologies developed also in our laboratory for accelerated modular-orthogonal synthesis of programmed structures such us Ni-catalyzed cross-coupling, mixed-ligand, thio-bromo click, SET-organic and polymerizarion reactions, self-accelerated and self-interrupted synthesis including selected examples of homochiral helical self-organizations and functions together with the molecular factory of life will be briefly explained. The origins of helical homochirality is equivalent to the origins of life although the origins and the rational of biological membranes homochirality continues to be debated [3]. Inspiration from amphiphilic Janus dendrimers [4a] and Janus glycodendrimers [4b] discovered in our laboratory allowed to transit from the commercial viral and four-component lipid nanoparticle synthetic vectors for delivery of mRNA to the one-component ionizable multifunctional sequence-defined amphiphilic Janus dendrimers (IAJDs) delivery vector [5]. The current status of the molecular design principles providing the least expensive and the simplest access to targeted delivery of mRNA with programmed IAJDs will be discussed in great details. Targeted delivery of mRNA to all organs is expected to change the field of nanomedicine at the most fundamental level by providing unprecedented avenues to new vaccines and therapeutics.
References

(a) Percec, V.; Xiao, Q. Bull. Chem. Soc. Jpn. 2021, 94, 900-928. (b) Percec, V.; Adamson, J.; Gianti, E. Supramolecular Nanotechnology, Wiley-VCH, 2023, Azzaroni, O.; Conda-Sheridan, M. Eds. Vol.1, p. 1-123. (c) Percec, V. Lab. Science 1997, 278, 449-452. (d) Nature 1998, 391,161-164. (e) Nature 2002, 419, 384-387. (f) Nature 2004, 430, 764-768.
(a) Pauling, L.; Corey, J. Am. Chem. Soc. 1950, 72, 5349-5349; (b) Watson, J. D.; Crick, F.H.C. Nature 1953, 171, 737-738; (c) Percec, V.; Xiao, Q. CHEM 2021, 7, 529-536; (d) Percec, V. CHEM 2023, August issue.
Percec, V. Lab. J. Am. Chem. Soc. 2023, 145, 4311-4323.
(a) Percec, V. Lab. Science, 2010, 328, 1009-1014; (b) Percec, V. Lab. J. Am. Chem. Soc. 2013, 135, 9055-9077.
(a) Percec, V. and Weissman D. Labs. J. Am. Chem. Soc. 2021, 143, 12315-12325; (b) J. Am. Chem. Soc. 2021, 143, 18803-12325; (c) J. Am. Chem. Soc. 2022, 144, 4746-4753; (d) Pharmaceutics 2023, 15, 1572; (e) J. Am. Chem. Soc. Submitted.

Virgil Percec was born and educated in Romania (BS in Organic and Macromolecular Chemistry at the Polytechnic University in Iasi, PhD in 1976 with C. I. Simionescu. In 1981 he defected his native country and after short postdoctoral stays at the University of Freiburg in Germany (July 1981 with H. -J. Cantow) and University of Akron, US (August 1981 to March 1982 with J. P. Kennedy) he joined the Department of Macromolecular Science of Case Western Reserve University in Cleveland, US in March 1982 as an Assistant Professor. He was promoted to Associate Professor in 1984 and to Professor in 1986. In 1993 he was awarded the Leonard Case Jr. Chair at Case Western Reserve University and in 1999 he was invited and moved to the University of Pennsylvania in Philadelphia as P. Roy Vagelos Chair and Professor of Chemistry. He has been repeatedly a Visiting Professor at the Universities of Freiburg, Ulm and at the Max Planck Institute for Polymer Research in Mainz (all in Germany) and at the Royal Institute of Technology in Stockholm. His research interest is at the interface between organic, supramolecular, macromolecular chemistries, liquid crystals, nanoscience and biology where he contributed over 820 refereed publications, 80 patents, edited 20 books and presented over 1300 endowed, invited and plenary lectures. He educated over 3509 students and postdocs over 70 of them being in university professors all over the world.

IBEC Seminar: Dr. Andy Tay
2023-09-15 10:00 - 11:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Biomaterials for cancer study and accelerate wound healing
Dr. Andy Tay , Assistant Professor, Presidential Young Professor, Department of Biomedical Engineering
Magnetic hydrogels are materials containing magnetic microparticles which help transduce magnetic fields into mechanical forces. In the presence of a static magnet, the stiffness of magnetic hydrogels can be altered to investigate the reversible effects of matrix softening and stiffening on cellular behaviours. Here, I will describe how we exploit this unique feature of our material for cancer study.
The World Health Organization estimates that 10% of the world’s population suffers from diabetes, and diabetic patients has a 15-25% lifetime risk of getting diabetic foot ulcers. Every 20s, there is a lower extremity amputation worldwide. In the second half of my talk, I will describe the use of magnetic hydrogel for mechanical stimulation of cells to synergistically accelerate diabetic wound healing.

Andy Tay graduated in 2014 from NUS with a First-Class Honours in Biomedical Engineering. He later headed to the University of California, Los Angeles for his PhD studies and graduated in 2017 as the recipient of the Harry M Showman Commencement Award. Andy next received his postdoctoral training at Stanford University before heading to Imperial College London as an 1851 Royal Commission Brunel Research Fellow. He is currently a Presidential Young Professor in NUS.
Andy is a recipient of international awards including the Interstellar Initiative Early-Career Faculty Award, Christopher Hewitt Outstanding Young Investigator Award, Terasaki Young Innovator Award. He is listed as a 2019 Forbes 30 Under 30 (US/Canada, Science), 2020 World Economic Forum Young Scientist, 2020 The Straits Times ‘30 and Under’ Young Singaporeans to Watch and 2022 Top 2% Scientist in the World by Stanford University.

IBEC Seminar: Mariano Vázquez
2023-09-27 12:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Supercomputer-based virtual humans: the future of medicine NOW
Mariano Vázquez, ELEM Biotech & Barcelona Supercomputing Center
In this talk we are going to address the potential of supercomputer-based virtual humans for the biomedical realm. Virtual Humans are computational “avatars” of a patient, which combines data with a mathematical model which are used to predict (as opposed to measure with experiments) some quantities of interest, under a context of use and used to support medical decisions. We will show examples of Populations of Virtual Humans used as cohorts for in-silico clinical trials to optimize drug or devise-based therapies.
Our examples are mostly of the cardiovascular and respiratory domains.

IBEC Seminar: New technologies for accelerating drug discovery and preclinical testing
2023-09-29 10:00 - 11:30 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
New technologies for accelerating drug discovery and preclinical testing
Maria Majellaro, Chief Scientific Officer of Celtarys.
Abi J Vazquez. Co-founder and COO of DIVERSA Technologies SL.
Bruno K Rodiño-Janeiro, Chief Scientific Officer of BFlow.

Celtarys, DIVERSA and BFlow belong to the Galician biotechnology ecosystem and are dedicated to provide cutting-edge technologies applied in different and complementary phases of preclinical drug screening, accelerating the drug development process and reducing the time to market of new therapies.
The three companies emerge from technologies developed at public research centers and transferred to the market after participation in validation programs. The speakers will explain their experiences in the process of going from an idea in the laboratory to the final technology transfer as spin-off companies.
Celtarys is a spin-off of the University of Santiago de Compostela, focused on the development of innovative fluorescent tools to improve the efficiency of the drug discovery process. In addition to its fluorescent ligand portfolio, Celtarys specializes in customized fluorescent ligands for target-based drug discovery, utilizing its proprietary conjugation technology. This unique approach allows to quickly design and develop libraries of different tailor-made fluorescent ligands with their own linkers covering wide chemical architectures for any target of interest.
DIVERSA is a spin-off from the Santiago de Compostela Health Research Institute (IDIS) and the Galician Health Service (SERGAS), devoted to drive the translation of new therapeutic molecules to the clinic through the application of patented safe-by-design lipid nanoemulsions that can efficiently improve the delivery of drugs and biomolecules (RNAs, proteins and peptides ) to their target, and thus efficacy. DIVERSA commercialize ready-to-use reagents, and also provides customized services for the development of tailored and unique formulations that can accomplish all requirements for a specific molecule, indication, and route of administration. We also conduct comprehensive R&D activities to advance our own nanomedicines towards the clinic, answering to current unmet clinical needs.

BFlow is a spin-off from the University of Santiago de Compostela (USC) and the Health Research Institute of Santiago de Compostela (IDIS), which offers advanced Organ-on-a-chip models to improve the physiological relevance of cell cultures. BFlow products are designed to cover the urgent need to improve the data in both research laboratories and the pharmaceutical industry. Regarding the latter, Organ-on-a-chip models will have a relevant role reducing the cost, time and use of experimental animal models in the preclinical drug screening process, accelerating the discovery of new drugs.

The seminar will consist of 15 minute talks from each company with 15 minutes of questions and answers.

IBEC Seminar: Simone Reber
2023-10-02 12:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Conserved nucleocytoplasmic density homeostasis drives cellular organization across eukaryotes
Simone Reber, Max Planck Institut for Infection Biology, Berlin (invited by Pere Roca-Cusachs)
The packing and confinement of macromolecules in the cytoplasm and nucleoplasm has profound implications for cellular biochemistry. How intracellular density distributions vary and affect cellular physiology remains largely unknown. We show that the nucleus is less dense than the cytoplasm and that living systems establish and maintain a constant density ratio between these compartments. Using label-free biophotonics and theory, we show that nuclear density is set by a pressure balance across the nuclear envelope in vitro, in vivo and during early development. Nuclear transport establishes a specific nuclear proteome that exerts a colloid osmotic pressure, which, assisted by entropic chromatin pressure, draws water into the nucleus. Using C. elegans, we show that while nuclear-to-cytoplasmic (N/C) volume ratios change during early development, the N/C density ratio is robustly maintained. We propose that the maintenance of a constant N/C density ratio is the biophysical driver of one of the oldest tenets of cell biology: the N/C volume ratio. In summary, this study reveals a previously unidentified homeostatic coupling of macromolecular densities that drives cellular organization.

IBEC Seminar: Jaap den Toonder
2023-10-11 11:00 - 13:00 | Sala Dolors Aleu, Cluster II, IBEC, Baldiri i Reixac, Barcelona
Microfluidic technology enabling biomedical applications
Jaap den Toonder, Microsystems Research Section, Department of Mechanical Engineering, and Institute for Complex Molecular Systems, Eindhoven University of Technology.
Currently, visiting professor at IBEC, Barcelona
Microfluidics is the science and technology of manipulating and analyzing fluid flow at small scales, typically from millimeters down to micrometers. At these scales, fluid flow is almost always laminar which enables excellent control over the flow. Microfluidic devices can be made using a range of microfabrication approaches and materials, and these enable to integrate tailored electronic or mechanical functions. These unique properties of microfluidic technologies, and the ongoing further development of the technology, enable a range of new biomedical applications, including diagnostic and monitoring devices, medical implants, and organ-on-chip.
In this lecture, I will present recent developments within three research lines of our lab. (1) Bio-inspired microfluidics: A novel microfluidic flow generation concept inspired by nature, which is based on magnetic nano- and micro-actuators we call “artificial cilia”; integrated in microfluidic devices, these can be used to induce flow, to manipulate particles, and as actuators in cellular mechano-transduction research. (2) Microfluidic devices for health: Examples of microfluidic devices for health applications, specifically a sweat sensing device for non-invasive semi-continuous monitoring of hospitalized patients, and a smart eye implant to control eye pressure in glaucoma patients after surgery. (3) Organ-on-chip: A game-changing technology in which human cells are cultured in microfluidic chips simulating and predicting the response of healthy and diseased human tissues. I will focus on cancer-on-chip approaches to understand initial stages of cancer metastasis, and on our lumen-based organ-on-chip models that are enabled by a 3D sugar printing technique we developed.

IBEC Seminar: Josep Puigmartí-Luis
2023-11-10 10:00 - 12:00 | 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.
