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Last week, after the final project meeting, took place the BLOC Symposium and Workshop at the Institute for Bioengineering of Catalonia (IBEC) with very interesting talks and a hands-on workshop to see, first hand, the benchtop NMR spectrometer developed during the project.

BLOC project is getting close to the end… Last 07^th of November BLOC researchers had the final meeting at the Consorci Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS) in Barcelona to debate the results and how to improve the benchtop NMR spectrometer. It was time for great discussions with the advisory board and all the project partners, and to think about future steps to bring this new technology closer to the clinic and the society.

Taking profit of the presence of most of the partners together in Barcelona, a Symposium and Workshop was organized at IBEC, on the 8^th of November, focused on the fields of MRI, NMR and hyperpolarization.  Renowned international researchers in these areas included Dan Vigneron (University of California), Steffan Glöggler (Max Planck Institute), Dragana Savic (INIA Biosciences & visiting scholar at University of Oxford) and Gabriele Stevanato (Università di Padova).

To finalize, the event was wrapped up with a round table about NMR and its applications in the field of biomedicine, with the participation of Michael Tayler (Photonic Sciences Institute, ICFO), Gabriele Stevanato, Dragana Savic, Andrea Capozzi, Dan Vigneron, Javier Sardina and Billy Halle (Oxford Instruments, OI).

It was a very fruitful moment to exchange ideas, reinforce networks and to construct new starting points for future exciting projects.

From 8th to 11st of November, BLOC project was present at the 2022 Barcelona Institute of Science and Technology (BIST) Conference on Precision Medicine. Researchers from the “Molecular Imaging for Precision Medicine” laboratory at IBEC presented scientific advances and participated in an outreach event with high school students.

The Barcelona Institute of Science and Technology (BIST) is a leading institution of multidisciplinary research encompassing seven Catalan research centres of excellence, including IBEC, coordinator of BLOC project. In the frame of the 6th edition of the BIST Conference, during 4 days more than 250 people from the BIST Community and its stakeholders shared their research advancements in precision medicine from multiple perspectives and approaches. Precision medicine involves patient-centred and comprehensive approaches to face healthcare, incorporating individual’s genetics, environment, and lifestyle viewpoints into targeted disease prevention and treatment plans.

In this scenario, Irene Marco-Rius presented the work being done in her laboratory at IBEC, that aim to develop molecular imaging tools to identify abnormalities of cell metabolism in human disease and predict treatment efficacy. She centred her talk on the subject of BLOC project and on use of NMR methods to identify biomarkers to diagnose, stage and evaluate treatment response in several diseases, in real time using so-called Hyperpolarization MR techniques.

On his side, Marc Azagra presented a flash talk entitled “High-throughput analysis in a microfluidic multiwell plate by non-invasive dynamic nuclear polarization-magnetic resonance”. He focused on the use of this high sensitivity technique, that is able to enhance the intrinsically low sensitivity of NMR up to 10,000 times allowing its extrapolation for real-time in-situ metabolomic analysis and its potential use as a preclinical tool.

Finally, Alba Herrero participated in an outreach activity in the framework of the 2022 “Setmana de la Ciència”, tailored to high school students. In total, about 2000 students could get in contact with precision medicine research projects explained in an easy way by PhD students. Alba gave an online talk and explained what “molecular imaging” is and how it can be applied to the field of precision medicine. 

Anna Novials and Vincent Ribes presented their research to members of the Diabetes Association of Catalonia. The visitors had the opportunity to learn a bit more about the disease and to know the cutting-edge research that is being carried out at IDIBAPS.

In the frame of a new communication project from IDIBAPS, researchers from BLOC Project at the Diabetes Pathogenesis and Prevention group received patients and their families from the Diabetes Association of Catalonia (ADC). ADC is a non-profit organization that supports research projects to develop new treatments, and why not to find a cure for diabetes. They give assistance to more than 600,000 people with the disease in Catalonia.

Anna Novials and Vincent Ribes showed IDIBAPS’s last advances in the field of diabetes research. Among the topics, they explained the BLOC Project and its objectives, aiming to develop a benchtop device based on NMR to detect and monitor metabolic diseases as diabetes to advance towards finding solutions and treatments to improve the life quality of patients. 

Visitors also had the opportunity to find out the cellular models with which the scientists work and to see the equipment that is used to analyse how exercise induces metabolic and molecular changes in patients with type 1 and 2 diabetes.

Sources:

https://www.clinicbarcelona.org/en/news/idibaps-receives-representatives-of-the-diabetes-association-of-catalonia

https://www.clinicbarcelona.org/en/news/representatives-of-the-diabetes-association-of-catalonia-visit-idibaps

Last 19^th of October it took place the 15^th edition of the IBEC Symposium, an annual meeting where bioengineering is in the centre of the scene.  Among several renowned national and international invited researchers, BLOC was present with a flash talk and a poster showing part of the work done at the “Molecular Imaging for Precision Medicine” laboratory at IBEC.

The 15^th IBEC Symposium was, in the words of IBEC’s director Josep Samitier, “a great opportunity to share our science, make new connections and also reconnect”. About 250 assistants joined together to present their research and discuss about how bioengineering can contribute to improve the life quality of society.  

In this scenario Marc Azagra presented a flash talk about the use of hight-throughput dynamic nuclear polarization (DNP)-nuclear magnetic resonance (NMR) imaging for real-time and non-invasive metabolic studies using microfluidic multiwell devices. The proposed method represents a new approach for hyperpolarization-enhance NMR experimentation that can be applied in the future as a preclinical tool to study diseases that affect cellular metabolism.

Additionally, Lluis Mangas presented a poster on the use of hyperpolarized nuclear magnetic resonance to study hepatocellular metabolism as part of his work in BLOC Project. Concretely, he focused on the development of a MR-compatible bioreactor platform for hepatocellular carcinoma metabolic analysis in real-time using a 60 MHz benchtop NMR spectrometer.

Researchers led by Javier Ramón-Azcón from the Institute for Bioengineering of Catalonia develop a “gym on a chip” that will help to study diabetes and find new drugs to treat the disease. The dispositive allow to study, in vivo, the crosstalk among different organs. In this paper, researchers combine muscle and pancreatic cells on a single chip and demonstrates that insulin production by the pancreas during exercise is induced by the contraction of muscle cells.

According to the World Health Organisation, 422 million people worldwide suffer from diabetes mellitus, and 1.5 million deaths each year are directly associated with the disease. Diabetes is a complex metabolic disease characterised by a high accumulation of glucose in the blood resulting from a failure in the production or activity of insulin. Insulin, in turn, is a hormone produced, stored and released by the pancreas, which enables glucose to enter the different cells of the body to provide them with the energy they need to function properly. Muscle is one of the main targets of insulin and is crucial in the overall maintenance of glucose levels throughout the body.

The development of new drugs to prevent and treat diabetes must be based on tools that take into account the communication between the pancreas and other organs in order to recreate the details of the disease. In a recent study published in the Advanced Materials Technology journal, IBEC researchers led by Juan M. Fernández-Costa and Javier Ramon-Azcon from the “Biosensors for Bioengineering” group, have developed a “multi-organ-on-chip” that allows, in a single device, to study the communication between the insulin-producing cells of the pancreas and the muscle cells. By using this innovative “gym on a chip”, researchers found that muscle cells contraction caused by electric stimulation directly induces the production of insulin by pancreatic cells.

The “gym on a chip”

The “multi-organ-on-chip” device engineered by the researchers have one compartment with skeletal muscle cells and another one with pancreatic islets composed of beta cells, which produce insulin. As these cells grow and develop, they form 3D structures that simulate a “mini-organ” inside the chip.

The muscle cells of the “multi-organ-on-chip” are connected to an electrical stimulator that simulates physical exercise and induces their contraction. In addition, the device is also integrated with a complex biosensor platform capable of monitoring insulin levels produced by pancreatic cells, and interleukin-6 (IL-6) levels without the need of external labelling. IL-6 is a regulatory protein that is produced by the muscle and signals the pancreas to increase insulin production. In other words, during exercise, IL-6 moves from the muscle to the pancreas to stimulate insulin production.

“With our “gym on a chip” we demonstrate that insulin secretion by pancreatic islets during exercise is dynamically mediated by the contractile activity of muscle cells and not by other intermediates”. Juan M. Fernández-Costa, first author of the study.

The new chip is a powerful tool for diabetes drug development and testing, and it allows personalised modelling of the disease by using patient’s own cells. With this model, researchers and clinicians will have the possibility to study diabetes following a new approach, by combining different cell types, and study in detail why insulin production by the pancreas sometimes fails.

In the future, the “muti-organ-on-chip” could also be used to study communication between other organs in the context of various metabolic diseases, providing a promising platform for new drug screening and personalised medicine.

Reference article: Training-on-a-Chip: A Multi-Organ Device to Study the Effect of Muscle Exercise on Insulin Secretion in Vitro. Juan M. Fernández-Costa, María A. Ortega, Júlia Rodríguez-Comas, Gerardo Lopez-Muñoz, Jose Yeste, Lluís Mangas-Florencio, Miriam Fernández-González, Eduard Martin-Lasierra, Ainoa Tejedera-Villafranca, and Javier Ramon-Azcon. Adv. Mater. Technol. 2022, 2200873.

Alba Herrero, Marc Azagra and Irene Marco-Rius from the Molecular Imaging for Precision Medicine Laboratory at IBEC, have developed a viable cryopreservation method to preserve bioengineered, three-dimensional (3D) cell models, including patients’ samples. The results of their work have been recently published on the Biomedical Materials Journal.

Cryopreservation of biological material as living tissue, cell lines and primary cells is a technique widely used in most molecular biology laboratories around the world. However, this technology was not adapted for its use on three-dimensional (3D) cell models. What Bloc researchers, led by Irene Marco-Rius, coordinator of BLOC project, have done now is to go a step further in this field and develop a viable protocol for spheroid cryopreservation and survival based on a 3D carboxymethyl cellulose scaffold and precise conditions for freezing and thawing.

By applying the new cryopreservation protocol, researchers were able to efficiently cryopreserve bioengineered hepatocytes, for which the scaffold provides both the 3D structure for cells to self-arrange into spheroids and to support cells during freezing for optimal post-thaw viability.

“The use of the 1% Carboxymethyl cellulose cryogel scaffold is crucial to procure support for the cells through the process as well as to aid in the removal of the cryoprotective agent after thawing for improved cell viability”.

This new protocol could be adapted for other bioengineered tissues and may be used to applications that demand high-integrity preservation and transport of pre-assembled 3D models, as cell lines and samples from patients. Moreover, the methodology described in this work pave the way for the development of protocols that simplify and reduce the cost and infrastructures required for the research with 3D cell cultures.

Reference article: Alba Herrero-Gómez, Marc Azagra, Irene Marco-Rius. A cryopreservation method for bioengineered 3D cell culture models. 2022 Biomed. Mater. 17 045023. DOI 10.1088/1748-605X/ac76fb

A Dynamic Nuclear Polarisation (DNP) Polariser for Nuclear Magnetic Resonance (NMR) has been recently installed at IBEC, coordinator of BLOC project, being the only one in operation in Spain, and among the few ones existing in Europe. This equipment can improve up to 10000 folds the signal compared to a conventional NMR procedure and allows for the study of cellular metabolism in real time.

The HyperSense™ equipment, from Oxford Instruments Molecular Biotools, has been recently installed in the Institute for Bioengineering of Catalonia (IBEC), at the Molecular Imaging for Precision Medicine laboratory (MIPMED) led by the coordinator of BLOC project, Irene Marco, following a cession agreement made with the University of Barcelona (UB).  This in vitro polarizer can provide a signal-to-noise ratio not reachable by conventional NMR equipment, increasing sensitivity by more than 10,000 fold. As a result, this technique can be used to study rapid metabolic processes either in vivo or in vitro, in a non-invasive way and in real time, providing information on the mechanistic and biochemical changes that occur in a diseased organ, for example. This powerful technique can open new areas of research and will probably change the field of NMR.

The European Project BLOC will strongly benefit from this recently installed equipment, as this forefront technology is crucial to fulfill its main objective: to develop a benchtop spectrometer based on magnetic resonance spectroscopy and imaging using dynamic nuclear polarisation (DNP-MR) to monitor metabolic diseases such as diabetes and non-alcoholic fatty liver disease (NAFLD) and evaluate responses to different stimulus.

The equipment installed at IBEC performs dynamic nuclear polarisation of samples in the fluid-form, for example sugars, that are afterwards used to monitor cellular metabolism on a conventional NMR equipment. The sample is transferred to the center of the HyperSense™, where it is submerged in liquid helium at the core of the magnetic field. Everything is done under an extremely low temperature, -271,75 ºC, which allows the sample carbon atoms to be nearly fully polarised.

BLOC researchers use hyperpolarised pyruvic acid, a sugar that is then used to study the metabolism of different cellular types. Inside the NMR, the cells are supplied with this sample and, for about 75 seconds, researchers can follow up its absorption by the cells and all the metabolic steps that use this sugar as energy source. This short time is sufficient to see several enzymatic reactions and transient metabolic reaction intermediates. In other words, this remarkable boost allows researchers to see molecular processes of different biological systems in real time, in situ, and in a non-invasive way, in just few minutes. Moreover, as it is a very fast procedure, problems such as temperature and oxygen changes, cell death and cellular alterations during the experiment are avoided, allowing researchers to reliably compare results among different experiments.

The hyperpolarised magnetic resonance technique allows us to observe in a couple of minutes what we could only see in hours with a conventional NMR, and moreover with a sensitivity that can be up to 10000 times higher.

Irene Marco, coordinator of BLOC project

The time-lapse video below shows the entire installation process of the HyperSense™ equipment, which took three days and counted with the participation of various skilled technicians.

 

 

Each 11 February we celebrate worldwide the International Day of Women and Girls in Science with the aim to eliminate gender stereotypes and long-standing biases that keep girls and women away from science. This year, BLOC participated with two talks to 11-12 years-old students to help normalizing the presence of women in scientific fields.

Since 2015, when the United Nations General Assembly declared 11 February as the International Day of Women and Girls in Science, this day is devoted worldwide to achieve full and equal access to and participation in science for women and girls. Through different actions and events, the idea is to further achieve gender equality promoting the empowerment of women and girls and promoting their participation in science.

In this scenario, BLOC contributed to this cause in the frame of the event “100tifiques”, organized by the Catalan Foundation for Research and Innovation (FCRI) and the Barcelona Institute of Science and Technology (BIST), an initiative that aims to bring science closer to schools and claim the female scientific talent around Catalonia.

Alba Herrero, researcher at the “Molecular Imaging for Precision Medicine” laboratory, and Bia Moreno, Communication Officer of the BLOC project, both from IBEC, gave talks to 11-12 years old students from two different schools. They explained her scientific trajectory and the ways that brought them to scientific fields: Alba is graduated in Biochemistry and is now doing her PhD, and Bia has a PhD in Molecular Biology.  Both focused her talks not only on scientific aspects, but also on personal and general aspects of their lives, with the objective to show to girls and boys that, despite being scientists, they also have a “normal” live!   

Diabetes is a metabolic disease occurring when glucose levels in the blood are too high, as a result of the malfunctioning on the production and/or action of insulin, a hormone produced by the pancreas. Last 25^th of January, Joan-Marc Servitja, a BLOC project researcher, gave a talk oriented to a non-scientific public to explain the causes of diabetes and the advances on this research field.

In the frame of a series of seminars organized by the Golferichs House Civic Center in Barcelona, in collaboration with the Institut de Recerca Biomèdica (IDIBAPS), last 25^th of January, Joan-Marc Servitja researcher from BLOC project at IDIBAPS, presented the talk titled: Why does the glucose level increase during diabetes? About 25 people learnt some general facts about diabetes, the factors that promote its development and what scientists are doing to fight against it from this top researcher.

Diabetes affects more than 420 million people worldwide, and it’s estimated that in only 25 years, by 2045, this number will reach 629 million. Joan-Marc drew the public’s attention to this alarming fact and talked about a “silent pandemic” that unfortunately is clearly growing. Another important fact is that diabetes is closely related with another pandemic:  obesity, result of a sedentary lifestyle and an unbalanced diet.

There are different types of diabetes, however type 2 is the most prevalent, affecting more than 80% of people suffering this disease. Type 2 diabetes is associated with obesity and aging, but despite being the most common form, is also the more reversible and the one we can prevent with healthy habits.

Joan-Marc explained that several organs participate in the control of glycemia, and focused his presentation on the pancreas, the organ responsible for the production of insulin. Insulin is a hormone that allows the glucose entering the cells, and thus is the responsible for the control of glucose levels in the blood. This hormone is produced by very specific cells from the pancreas, known as beta cells, which are present in the pancreatic islets that in fact account for only 2% of the entire organ.

 

 

The second half of his presentation was devoted to talk about the efforts being done by researchers worldwide to understand diabetes in detail and to find new ways to detect the disease and discover efficient drugs to treat it. In this scenario, Joan-Marc presented BLOC project as a new technology to study metabolic diseases as diabetes in a non-invasive way by using nuclear magnetic resonance. This technology allows the analysis of hundreds of metabolites in real time to find out what is changing during the disease and see the effect of a certain drug. Moreover, he highlighted the need to reduce animal experimentation by developing new tools that simulate organs and metabolic diseases in the laboratory.

 

You can watch the entire talk (in Catalan) here:
https://youtu.be/utd1e74h1A0

Dr. Joan-Marc Servitja is researcher at the Pathogenesis and Prevention of Diabetes Group from the Institut de Recerca Biomèdica (IDIBAPS) and the Networking Biomedical Research Centre (CIBERDEM).

Last 24^th of September took place another “European Researchers’ Night”, a Europe-wide public event that aims to bring the diverse science fields closer to the society in a funny and easy way. This year, more than 300 cities in 29 different countries participated proposing activities and experiences.

Researchers from BLOC project and the Molecular Imaging for Precision Medicine group at IBEC, Irene Marco-Rius, Alba Herrero, Marc Azagra and Gergo Matajsz, took this opportunity to explain why imaging plays such an important role in science. They participated in a Research Fair promoted by “La Caixa Foundation” that took place at the  Cosmo Caixa Museum in Barcelona. More than 100 people had the opportunity to learn about imaging techniques and their influence on their daily lives, experiencing science in first-hand thanks to family-friendly activities and experiments, and live demonstrations.

Additionally, Irene Marco-Rius participated in another initiative called “The research morning”, also in the frame of “Researchers’ Night” but oriented to schools. She gave a talk at the Bernat Metge high school for twenty 16 year-old students. The topic was “what’s like to investigate in molecular imaging” and among others, she explained techniques such as nuclear magnetic resonance and bioengineering to the students, who showed lot of interest by asking many questions. These kind of events are also important to clarify stereotype concerns about the figure and life of scientists and helps to create scientific vocation among young people.

 

 

The European Research Night is a European scientific dissemination project promoted by the European Commission within the framework of the Marie Skłodowska-Curie actions of the Horizon 2020 program.