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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.

BLOC is a European Project that brings together different academic and industrial partners to improve a new technology that integrates tissue engineering and magnetic resonance spectroscopy using dynamic nuclear polarisation (DNP-MR), to monitor diabetes and liver diseases.

Dr. Vicent is a biochemist with a strong background in the study of metabolism. The last years he dedicated his research to understand the impact of metabolic diseases on liver function, using animal and cellular models. His knowhow is crucial for BLOC project, where he validates and interprets the measurements of DNP-NMR with in vivo models of metabolic diseases. You can check here a short video, where he describes his role in BLOC project and shows some of the work he is carrying out at IDIBAPS, and an interview where he explains in more detail some aspects of his professional profile and other topics related to the project.

1) Can you describe yourself in a couple of lines?

I am a biochemist originally from Ibiza in Balearic Islands. During my career I have been interested in metabolism and how it affects our quality of life. First, I did my PhD at the Hospital Sant Pau in Barcelona on atherosclerosis. Then I performed a postdoc at the IRB Barcelona studying diabetes and I moved to the UCLA in California for four years, where I was studying the gender-specific differences in the metabolic syndrome. Afterwards, in the last eight years, I have been investigating on how metabolic diseases impact on liver function and how can drive cancer.  For all these research studies I generated and used different models such as genetically engineered mice, cells or virus, and also with clinical data from human subjects.

2) What is your role/position within BLOC?

Given my experience in animal and cellular models for metabolic disease my role as a postdoctoral scientist is to obtain and describe in vivo models of metabolic diseases to check and validate if the measurements of DNP-NMR can detect these metabolic disturbances and how to interpret these results for the evaluation of the disease and its treatments.

3) Could you tell us a little bit about the concrete work you are involved in inside BLOC project? What are you currently working on/which experiments are you carrying out?

Right now I’m mainly involved in two different lines of research. First, there is a line working on in vivo experiments where I am evaluating type two diabetes, obesity and fatty liver disease mouse models for their use in the DNP-NMR to detect meaningful changes in the metabolism in live animals. Second, along with some of other scientists of the BLOC project, I’m working on setting up in advanced engineered in vitro models of these metabolic diseases in cultured cells to make them to be as similar to the original tissue and design them to fit into the system to use in the DNP-NMR analysis.

4) What are the expected results? What is the expected impact of the work you are doing? Why is this relevant for the project/for the goal of the project?

We need to have reliable and reproducible models to detect the changes in metabolism that are relevant in the metabolic disease and therefore validate the results that we obtain with the DNP-NMR. We expect to have a range of different animal models to check these metabolic fluxes and also different engineered in vitro cultured cells that are able to recapitulate these changes. These models will be very important both to validate this new technology but also to have reliable models for the study by DNP-NMR of human metabolic diseases.

5) How do you feel about being a part of this European Project? How is it to work with other partners around Europe?

I feel very excited to work in this multidisciplinary team because it broadens your point of view of the scientific challenges. I worked in academic, clinic and basic science projects before; however, I find this particular project very interesting because it combines biochemistry, biotechnology and engineering, so I’m learning a whole new vision. Working in this integrative environment brings new opportunities, new perspectives and revolutionary solutions that would be impossible otherwise.

The other members of the BLOC Consortium are: IBEC, Oxford Instruments and Multiwave Technologies.
If you want to know more about the project and the other partners, check the BLOC project webpage.

BLOC co-coordinator Javier Ramón from IBEC led a work recently published in the Journal Biofabrication describing a new technology that increases the performance of pancreatic cells grown in vitro and induces their organization in β-cell clusters, similarly to the spheroid-like structures found in vivo. This new technology will be crucial to develop BLOC’s benchtop NMR to study metabolic diseases as diabetes. 

Pancreatic islets are responsible for maintaining glucose homeostasis by secreting the hormones insulin and glucagon. When cells from peripheral tissues cannot properly use this insulin, an imbalanced situation occurs that may end with the development of type 2 diabetes, characterized by an excess of glucose. This chronic metabolic disorder is considered a global pandemic affecting more than 400 million people worldwide. Despite its prevalence, research in this field have been classically based on the use of monolayer cell cultures that do not accurately reproduce the in vivo physiology of pancreatic islets, limiting to reveal naturally occurring processes and reducing the consistency of in vitro experiments.

To face these constraints, researchers led by Javier Ramon developed a scaffold based on carboxymethyl cellulose (CMC) cryogels, improving its mechanical and physical properties when compared to gelatin-based scaffolds. This new scaffold allows to engineer pancreatic cells, generating β-cell clusters and creating specific range pseudoislets. In summary, they can reproduce in vitro the round-shaped cell aggregations of around 100 µm in diameter that form the pancreatic islets. Besides these advantages, the new scaffold also increases the cell viability for up to 7 days and the response to glucose over conventional monolayer cultures.

The new scaffold developed in this work is a key point to attain the main objective of BLOC project, as it will allow to satisfactorily engineer the pancreatic islets that will be used in the benchtop nuclear magnetic resonance (NMR) to study metabolic diseases as diabetes. The use of a suitable 3D tissue engineering system makes possible to precisely position the cells to simulate the native structure of the tissue under study.

Reference article: Cellulose-based scaffolds enhance pseudoislets formation and functionality. Ferran Velasco-Mallorquí; Júlia Rodríguez-Comas and Javier Ramón-Azcón. 2021. Biofabrication 13, 035044.

You can read the complete publication here:
Cellulose-based scaffolds enhance pseudoislets formation and functionality – IOPscience

The coordinator of BLoC project, Irene Marco-Rius, has been recently selected to participate in the new “la Caixa” Foundation – BIST Chemical Biology Programme and begin her own research group as principal investigator, the “Molecular Imaging for Precision Medicine group».

The young talent and research excellence of Irene Marco-Rius has recently been recognized by the “la Caixa” Foundation – BIST Chemical Biology Programme, a new programme that aims to launch a powerful research programme in chemical biology, and to attract talent through the creation of a hub in Barcelona focused on this discipline. Irene is a physicist, holds a PhD on magnetic resonance spectroscopy by the University of Cambridge, and has an international profile that counts with several stays in the USA and in different European countries. Through this programme, started last April, she will receive funding to begin her own research group as principal investigator at the Institute for Bioengineering of Catalonia (IBEC). Her laboratory, named “Molecular Imaging for Precision Medicine group”, will focus on developing innovative molecular imaging technologies to diagnose diseases and assess early response to treatments.

My research focuses on developing technology to diagnose disease and evaluate response to treatment without any pain and without the need for a biopsy. In fact, we use a magnetic resonance imaging device that allows us to monitor chemical reactions and informs us on the health status of the cells inside the human or animal body, or in bioengineered tissues.

A new chapter in the scientific trajectory of Irene is beginning now, and this change implies that from now on she will assume the coordination of BLoC project as principal investigator, while Professor Javier Ramón will continue his participation as co-coordinator.

About the “la Caixa” Foundation – BIST Chemical Biology Programme

The idea behind this newly created “la Caixa” Foundation – BIST Chemical Biology Programme is to take advantage of the very developed biopharmaceutical sector present in the region of Barcelona to establish new multidisciplinary chemical-biology research lines that will culminate with the development of novel biomedical approaches and innovative drugs to treat diseases. Chemical biology applies the quantitative techniques of chemistry to the study of biological processes that occur in living organisms, being a research area with high relevance for the field of medicine.

“la Caixa” Foundation supports excellent research in health and biomedicine in Spain and Portugal stimulating innovation and the transfer of knowledge from the laboratories to new treatments and solutions for patients. The foundation acts by promoting generation of new knowledge in key biomedical areas and the improvement of medical and clinical practice. They also support basic research and the dissemination of the results to the society.

On the other hand, the Barcelona Institute of Science and Technology (BIST) is a leading institution of multidisciplinary research formed by seven Catalan research centres of excellence, including IBEC. BIST aims to promote excellent research in a multidisciplinary environment, fostering collaboration among the members of this diverse scientific community to become a global reference for training outstanding research talent and to maximize science impact in society.

The Chemical Biology Programme initiative aims to attract talent from the field of chemical biology and to create an ecosystem that fosters research excellence in improving health.

An article about BLOC project was recently published on Cordis EU Research Results. It gives an overview of the project, including the technology and proof-of-concept, and talks about its innovative aspects and how the results can impact on biomedicine and reach the society.

BLOC project is creating an innovative technology to monitor diseases and cellular responses to various stimuli, using dynamic nuclear polarisation (DNP-MR) techniques and a benchtop nuclear magnetic resonance (NMR) spectrometer. Researchers are working on a piece of equipment to observe the metabolism of tissues engineered with cells in an easy and non-invasive way, filling the actual gap in metabolic studies that use simple 2D in vitro cell cultures.

Imagine that your doctor could observe the response of your own cells to a specific drug during a routine consultation. The doctor could test if the treatment you apparently need will have the expected effect and know your body’s reaction in advance. By doing so, lots of time (and money) would be saved, but more importantly, it could mean a considerable reduction of secondary effects for you and choosing the right drug for you. It seems science fiction, but it is closer than you might think.

BLOC is a European project that is working towards enabling precisely that. A consortium composed of different European academic and industrial partners is developing new technology to study the metabolism of tissues in real time.

New technology to see the metabolism in real time

To fully utilize biological systems, it is crucial to understand the systems’ complexity from molecular to multi-organ level. Pharmaceutical industry relies heavily on in vivo animal models and in vitro two-dimensional (2D) cell cultures to develop therapeutic strategies. There are many ethical issues surrounding experimentation in animals, and also serious concerns regarding their biological relevance, because the capacity to extrapolate animal model data to human conditions is limited.

Although current in vitro tissues are useful to study molecular and cellular processes, there are some limitations as they do not cover the complexity of the physiological microenvironment in which cells grow. Current 2D tissue models often do not simulate complex cell-cell and cell-matrix interactions, crucial for regulating cell behaviours in vivo. Due to these shortcomings, there is now substantial interest and need in developing fully functional 3D tissues that closely mimic the in vivo system for disease modelling and chemical testing, such as bioengineered organs.

BLOC will develop new technology based on a benchtop nuclear magnetic resonance (NMR) spectrometer and dynamic nuclear polarisation (DNP-MR) for metabolic readout of 3D in vitro models to monitor disease and evaluate responses to different stimulus. The use of a 3D tissue engineering approach renders precise positioning of cells and defines cells’ interactions with their surrounding environment, mimicking the 3D structure of native tissue constructs. The novelty of this technology is the use of a small NMR spectrometer that can fit in any bioengineering laboratory and dissolution DNP, which increases the MR signal of endogenous 13C-labelled metabolites by a factor of more than 10,000 relative to the physiological background. Metabolites hyperpolarised by DNP and injected into cells and tissues enable real-time quantitative assessment of metabolite flux and spatial distribution non-invasively.

Diabetes and liver diseases as proof-of-concept

Diabetes and non-alcoholic fatty liver disease (NAFLD) are significantly increasing worldwide. NAFLD is strongly associated with obesity, insulin resistance and dyslipidaemia. On the other side, type 2 diabetes, the most common form of this disease (90–95% of cases), is preceded by a prediabetic stage characterised by insulin resistance. Despite the high prevalence of both diseases, there are currently no methods to predict their metabolic onset, disease progression and treatment efficacy. A key step to face this problem is to develop a technology able to provide precise diagnostic and metabolic analysis at an economically affordable cost.

As a proof-of-concept, BLOC project will fabricate a biomimetic model composed of liver cells and pancreatic islets and develop the necessary benchtop NMR hardware and software to study such metabolic diseases. The study of the crosstalk between different cell populations in the liver and pancreas would broaden our understanding of complex systems contributing to metabolic diseases. BLOC technology is expected to be available for society in the next few years.

Keywords
health, tissues, NMR, research, technology, cells

BLOC is a European Project that brings together different academic and industrial partners to improve a new technology that integrates tissue engineering and magnetic resonance spectroscopy using dynamic nuclear polarisation (DNP-MR), to monitor diabetes and liver diseases.

Alba Herrero is a research assistant working at IBEC in the frame of BLOC. Her background and previous research experience in multidisciplinary fields add high value to the project! You can check here a short video where she briefly describes a typical work day in the lab., and also an interview where she explains in more detail some aspects of her professional profile and her role in BLOC project. Enjoy it!

1) Can you describe yourself in a couple of lines?

My name is Alba Herrero Gómez, and I am originally from Terrassa, Barcelona. I moved to New Jersey in 2015 to study a BS in Biochemistry and play basketball in the university’s team. During my time at Georgian Court University, I joined a research laboratory on analytical chemistry and developed a project focused on NMR and Raman spectroscopy. When I graduated, I moved to New York to study a Master’s in Biotechnology, and I became a professor at the university for the Biology department. During my time at the College of Staten Island I joined a Cancer research lab and developed a multidisciplinary project on Photodynamic Therapy in cancer cells. When I graduated, I moved back home and started a Research Assistant position at IBEC to work on the tissue engineering aspect of the BLOC project.

2) What is your role/position within BLOC?

I work on the tissue engineering part of the BLOC project. I am working on developing the liver model to study diabetes and NAFLD metabolism. While working on the liver model I collaborate with the engineering team to develop ways to reduce the strain on the cells involved in the experiment. We aim to troubleshoot shortcomings from our system to make our platform as efficient as possible for DNP-NMR analysis.

3) Could you tell us a little bit about the concrete work you are involved in inside BLOC project? What are you currently working on/which experiments are you carrying out?

One of the main challenges is to develop a physiologically accurate liver model for disease study that is compatible with the DNP-NMR technique and allows for cell growth and survival. So far, we are testing the viability of the cells, structural distribution, and metabolic activity inside the model. The challenge I am tackling right now is to induce NAFLD and diabetes on the healthy cells while keeping as many physiological functions as possible, focusing the accuracy and reproducibility of the model. Since the model presents such a challenge itself, it is important to simplify the modeling technique as much as possible to make the procedure accessible without losing physiological fidelity.

4) What are the expected results?

We expect to have a physiologically accurate model that is compatible with DNP-NMR and other spectroscopic and imaging techniques for diagnosis. We also expect to develop a system that reduces the strain on cells during the experiment while allowing for an efficient data acquisition and analysis.

5) What is the expected impact of the work you are doing? Why is this relevant for the project/for the goal of the project?

With an efficient tissue engineering model, we will be able to further develop our data acquisition technique and obtain biologically relevant results, reducing the need to use laboratory animals for the validation of our results in vivo. Creating a benchtop NMR platform and making it accessible will allow for the easy use of NMR in the laboratories that choose to use this technology for their studies, helping spread knowledge about NMR and its multiple functionalities.

6) How do you feel about being a part of this European Project? How is it to work with other partners around Europe?

Being part of such a multidisciplinary project is both challenging and exciting. All the researchers involved in the project bring something to the table and even though we come from different scientific fields and backgrounds is empowering to be able to find solutions together and share our knowledge to develop the project.

The other members of the BLOC Consortium are: Oxford Instruments, Multiwave Technologies and IDIBAPS.
If you want to know more about the project check the BLOC webpage.