News

Improving quality of MR spectra from mouse brain. MRSI-detected pattern in glioblastoma patients

Work performed at Unit 25 of Nanbiosis ICTS of “NMR: Biomedical ApplicationsI” is being shown at the Joint annual meeting ISMRM-ESMRMB (May 7-12th) London, with the participation of CIBER-BBN group members Ana Paula Candiota, Silvia Lope-Piedrafita, Miquel Cabañas (abstract 1), Carles Arús, Gulnur Ungan, Margarida Julià-Sapé, Alfredo Vellido and Carles Majós (abstract 2).

In the first abstract, entitled “High resolution Multi-voxel spectroscopy using CSI-semi-LASER for mouse brain preclinical studies” we focused into improving quality of MR spectra obtained from mouse brain, a key factor when trying to pursue metabolomic-based biomarkers.

The second abstract, entitled “MRSI-detected pattern in glioblastoma patients one month after concomitant chemoradiotherapy” presented a study with a retrospective MRSI set of 31 glioblastoma patients and investigation of spectral patterns predictive of true progression or pseudoprogression.

The International Society for Magnetic Resonance in Medicine (ISMRM) and The European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) are prestigious scientific societies devoted to magnetic resonance-based studies at international and European levels with participation of the most renowned scientifics in the field. This year, the international and european events are joined into a single event (https://www.ismrm.org/22m/)

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Induced pluripotent stem cells in disease modelling and experimental therapies: cardiovascular perspective

On the 20th of May, we will be receiving an international visit at the Unversity of Zaragoza from Pr. Józef Dulak from Jagiellonian University, Kraków, Poland. The title of the talk will be “Induced pluripotent stem cells in disease modelling and experimental therapies: cardiovascular perspective“.

The invited lecture is programed within the framework of the European CISTEM project, in wich the University of Zaragoza participates through CIBER-BBN group TME lab – NANBIOSIS U13 Tissue & Scaffold Characterization Unit.

The event will take place at 12:00 in the I3A SEMINAR (2nd floor) of Campus Rio Ebro, of University of Zaragoza

Induced pluripotent stem cells (iPSC) are generated by genetic reprogramming of somatic cells and thanks to the ability to differentiate into almost all cells types of the organism they offer the enormous possibilities for investigating disease mechanisms, drug sensitivity and safety and for experimental regenerative approaches. iPSC thus became the indispensable tools of current medial biotechnology and received additional input thanks to the development of the CRISPR/Cas9 gene editing.

In this lecture PR. Józef Dulak will review his research in which iPSC and CRISPR/Cas9 gene editing is applyed for investigating the iPSC-differentiation to cardiomyocytes, endothelial cells and other cell types linked with the disease affecting vascular system, heart and the skeletal muscles. The special attention will be on discussing the potential of iPSC for diabetes and Duchenne muscular dystrophy disease modelling.

Application of iPSC-derived cardiomyocytes offer the chance for effective cell therapy of heart failure and this will be addressed in regard to recently published studies.

Sci Rep. 2015 Feb 26;5:8597. doi: 10.1038/srep08597.
Stepniewski J, et al., Dulak J. Heme oxygenase-1 affects generation and spontaneous cardiac differentiation of induced pluripotent stem cells. IUBMB Life. 2018 Feb;70(2):129-142. doi: 10.1002/iub.1711. 2018 Jan 9.
Kachamakova-Trojanowska N, Stepniewski J, Dulak J. Human iPSCs-derived endothelial cells with mutation in HNF1A as a model of maturity-onset diabetes of the young. Cells. 2019 Nov 14;8(11). pii: E1440. doi: 10.3390/cells8111440.
Stępniewski J, et al. Dulak J. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes, in Contrast to Adipose Tissue-Derived Stromal Cells, Efficiently Improve Heart Function in Murine Model of Myocardial Infarction. Biomedicines. 2020 Dec 7;8(12):578. doi: 10.3390/biomedicines8120578.
Jeż M, et al. Dulak J. Role of Heme-Oxygenase-1 in Biology of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells. Cells. 2021 Mar 1;10(3):522. doi: 10.3390/cells10030522.
Andrysiak K, Stępniewski J, Dulak J. Human-induced pluripotent stem cell-derived cardiomyocytes, 3D cardiac structures, and heart-on-a-chip as tools for drug research. Pflugers Arch. 2021 Jul;473(7):1061-1085. doi: 10.1007/s00424-021-02536-z. Epub 2021 Feb 24.
Martyniak A, et al, Dulak J. Generation of microRNA-378a-deficient hiPSC as a novel tool to study its role in human cardiomyocytes. J Mol Cell Cardiol. 2021 Jul 28;160:128-141. doi: 10.1016/j.yjmcc.2021.07.007.
Kachamkova-Trojanowska N, Skoczek D, Dulak J, Maturity Onset Diabetes of the Young – new approaches for disease modelling. Int J Mol Sci. 2021 Jul 14;22(14):7553. doi: 10.3390/ijms22147553.
Andrysiak K, et al., Dulak J. Generation of DMBi002-A human induced pluripotent stem cell line from patient with Spinal muscular atrophy type 3. Stem Cell Res. 2021 Oct 13;57:102563. doi: 10.1016/j.scr.2021.102563.
Jelinkova S, Martyniak A, Dulak J, Stępniewski J. Derivation of human pluripotent stem cell line via CRISPR/Cas9 mediated deletion of exon 3 LAMA2 gene (DMBi001-A-1) Stem Cell Res. 2021 Sep 2;56:102529. doi: 10.1016/j.scr.2021.102529

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OPEN SUBMISSION FOR JOURNAL SPECIAL ISSUE ON OLIGONUCLEOTIDE BASED THERAPIES

Dr. Ramon Eritja, Scientific Director of NANBIOSIS unit 29 of Oligonucleotide Synthesis Platform (OSP) and Dr. Santiago Grijalvo researcher at NANBIOSIS unit 12 of Nanostructured liquid characterization, from CIBER-BBN and IQAC-CSIC, together with Dr. Andreia F. Jorge, from Coimbra Chemistry Centre (CQC), acting as guest editors of journal Pharmaceutics, of MDPI Publisher, welcome authors to submit their articles on special issues on Recent Trends in Oligonucleotide Based Therapies.

In the past few decades, significant efforts have been made towards the clinical application of oligonucleotides. However, the potential of the therapeutic applications of RNA-based strategies have recently been spotlighted after the first approval of mRNA vaccines in response to COVID-19 pandemic. These molecules have the power to tackle targets that are usually considered to be “undruggable” by blocking the translation or transcription of a specific gene by stimulating the degradation of a particular messenger RNA.

This Special Issue aims to collect reviews, original research articles, and short communications covering innovative strategies in the design, synthesis, and characterization of therapeutic oligonucleotides as well as advances in their delivery based on nanotechnologies. Research concerning the study of sequence-specific protein–DNA/RNA interactions will be also considered.

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form.

For all the informations and instructions about the Special Issue, please visit this MDPI page

Deadline for submissions: 31 December 2022

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Wide representation of NANBIOSIS research in NALS 2022 and best Oral Presentation to Eloi Parladé

During the last 27-29 April, the 3rd International Conference on Nanomaterials Applied to Life Sciences 2022 (NALS 2022) has taken place in the Excellence Campus of Universidad de Cantabria in Santander (Spain), organized by the University of Cantabria and Institute Valdecilla-IDIVAL.

NALS 2022 has been a multidisciplinary conference series sharing new results and ideas in the fields of biosensors, lab on a chip, drug delivery nanopharmacy. nanobiotechnology, intelligent nanomaterials, magnetic materials, nanotoxicity, antimicrobials, novel applications of 3d bioprinting and nanoimaging.

NANBIOSIS has been represented at this edition by members of several of its units, among them we must highlight the set of four oral communication presented by members of the Nanobiotechnology group-Unit 1 of NANBIOSIS “Protein Production Platform (PPP)”, from CIBER-BBN and IIB-UAB the talks were delivered by:

Eloi Parladé: “Development of ion-dependent microscale secretory granules for nanomedical applications”

Carlos Martínez-Torró: “Design of a human GFP-like protein scaffold for targeted nanomedicines”

Eric Voltá Durán: “Antitumoral nanoparticles with multiple activities, a close reality”

Jan Atienza-Garriga: “Characterization of protein-only NPs containing amps and analysis of their protection with liposomes and micelles”

They summarized a wide area of the team activities on the design of protein-based protein materials for clinical uses, produced by means of diverse types of cell factories. In particular, antimicrobial peptides, cytotoxic proteins with antitumoral targeting and drug-carrying scaffold proteins are engineered to confer self-assembling properties as either microparticles or nanoparticles, that can be further functionalized with chemical drugs through covalent binding. Microparticles are of special interest as they can be used as slow drug delivery systems for nanostructured drugs upon subcutaneous administration. Alternatively, nanoparticles can be also presented as embedded in liposomes or other micellar structures that stabilize them for enhanced performance.

Three NANBIOSIS units supported the presented research, which has been executed in a highly cooperative way: namely U1 (Protein Production Platform), led by Tony Villaverde U18 (Nanotoxicology), led by Ramón Mangues and U29 (Oligonucleotide Synthesis Platform), led by Ramón Eritja.

Among all the excellent contributions by the team, it is worthy to stress that the prize for the best Oral Presentation was granted to Dr Eloi Parladé.

Other talk by researchers from NANBIOSIS were “Antioxidant-loaded polymeric NPs prepared by nano-emulsion templating for the management of neurological diseases” by Santiago Grijalvo, from NANBIOSIS U12 and “Exploiting GSH oxidation with nanocatalysts to promote cancer cell death” by Javier Bonet-Aletá from NANBIOSIS U9

On the other hand, Jesús Santamaría, Scientific Director of NANBIOSIS U9 was a Keynote Speaker in the Conference with the talk: “A change of paradigm in cancer therapy? Using catalysts to make drugs inside the tumor, rather than trying systemic chemotherapy”

NALS 2022 has been an excellent conference, with presentations covering a wide range of topics in nanomaterials for health, and a great opportunity for our researchers, especially for young’s, to let know their collaborative work, as well as make new connections on common research interests, thanks to the good socializing opportunities afforded by the scheduling of the organization conference.

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CRISPR technologies for Cystic Fibrosis treatment

Cystic fibrosis is an inherited genetic disease that mainly affects the lungs and the digestive system

On April 6, the first meeting was held, on the one hand, with people with Cystic Fibrosis and the Euskadi Cystic Fibrosis Association (Arnasa) and, on the other, with the NanoBioCel research group of the CIBER-BBN and the University of Basque Country, which is also part of the ICTS Nanbiosis through the Drug Formulation Unit U10.

The cooperative relationship between the NanoBioCel research group and Arnasa began approximately 5 years ago with the contributions made by the association to the NanBioCel group for research in cystic fibrosis.

The goup has focused on the development of non-viral vectors to address the treatment of cystic fibrosis through gene therapy. Progress is currently being made in the development of CRISPR technologies for its treatment.

This meeting was organized with the main objective of making those affected aware of the research carried out by NanoBioCel in cystic fibrosis and promoting associationism and collaboration between affected people and researchers to better understand the disease and find promising solutions.

The event was attended by almost 28 associates and many of the rest requested that the presentation of the researchers be recorded

Arnasa is the Cystic Fibrosis Association of the Basque Country and contributes with its work and activities to the promotion of general interest and the visibility of the disease, as well as to the improvement of the quality of life of people affected by the disease and their families.

In the picture: Increased activity of the chloride channel in CUFI cells transfected with non-viral vectors.

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New Summer School “The medicine of the future: Nanomedicine”

From 11 to 15 of July 2022 will take place the Nanomed-CSIC Summer School, organized by the Menéndez Pelayo International University (UIMP), with the sponsorship and collaboration of the CSIC.

The Nanomed-CSIC Summer School brings together scientific experts from all over Spain in different fields of nanomedicine and is aimed at all research staff and students, at any stage of basic or advanced scientific training.

There are scholarships from the Menéndez Pelayo International University (UIMP) which application period ends on May 3, 2022. For further informations and appalications follow this link

The course reviews the latest international advances in areas such as personalized nanomedicine, nanopharmaceuticals for the heart, nanomaterials for clinical diagnosis, the use of nanoparticles in molecular imaging and discovers how metallic nanoparticles are obtained, as well as the identity biology of nanomaterials or antimicrobial nanomedicine.

The program includes 2 plenary talks, 2 daily thematic talks and round tables. The aim this summer school is to promote public participation and provide a global vision of the opportunities and challenges that nanomedicine represents in the four areas of study that will be developed at the school: nanoTherapy, nanoDelivery, nanoSensors and nanoDiagnosis, summarizing the main advances in the application of nanomedicine.

This summer school will be held face-to-face in Santander and remote connection will be available to follow the event

For futher information, program and registration for the Summer School visit UIMP

Nanomed CSIC Connection

Nanomed Connection is a scientific collaboration network created by CSIC in October 2021 to promote research in nanomedicine. The new network promotes a multidisciplinary approach to nanomedicine research to share knowledge and encompasses chemists, physicists and biologists.

NanomedCSIC is a platform open to all CSIC groups with active research in nanomedicine, which will promote this discipline through the application of technology at the atomic and molecular level to improve the detection and treatment of cancer, cardiovascular diseases and infectious pathologies, among others.

NANBIOSIS ICTS and Nanomed CSIC Connection

Sharing focus, lines and objectives, both networks collorate in the promotion and dissemination of nanomedicine research. The researchers leading the NANBIOSIS units created by CIBER-BBN at CSIC centers are active members of Nanomed CSIC Connection.

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OPEN SUBMISSION FOR FRONTIERS IN CHEMISTRY SPECIAL ISSUE ON NUCLEIC ACID-BASED APTAMERS IN THERAPEUTICS AND DIAGNOSTICS

Dr. Anna Aviñó, Scientific Coordianator of NANBIOSIS unit 29 of Oligonucleotide Synthesis Platform (OSP) and Dr. Carme Fàbrega from the Nucleic Acid Chemistry group from CIBER-BBN and IQAC_CSIC, together with Dr. Claudia Riccardi from the University of Naples Federico II, Dr. Stefania Mazzini from University of Milan, and Dr. Raimundo Gargallo from the University of Barcelona, acting as guest editors of the journal Frontiers in Chemistry, welcome authors to submit their articles on special issues on Nucleic Acid-Based Aptamers in Therapeutics and Diagnostics.

Nucleic acid‐based aptamers are short DNA or RNA sequences able to adopt specific three‐dimensional architectures. The high affinity and selectivity shown for a selected target, as well as the wide range of molecular targets, make aptamers a valuable alternative to antibodies in several biological applications.

Oligonucleotide-based aptamers have become an attractive tool not only in molecular biology research but also in modern medicine as precision instruments for molecular diagnostics, as sensing device and in therapy (as drugs or drug-delivery systems). Numerous improved methodologies for their selections and various applications, such as bioimaging, diagnoses, molecular therapies, and nanotechnology, have been reported to date.

This Research Topic will concentrate on the latest development’s nucleic acid-based aptamer chemistry. We encourage authors to submit original research and review articles dealing with all the aspects of aptamer research, including aptamer selection technology, engineering/modification strategies, characterization, development, and/or application of aptamers in therapeutics and diagnostics.

Manuscripts should be submitted on line on the following link.

Deadline for submission: 26 May 2022

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NANBIOSIS renews its accreditation as Singular Scientific and Technical Infrastructure (ICTS)

The Minister of Science and Innovation, Diana Morant, chaired the XI meeting of the Council for Scientific, Technological and Innovation Policy, in which the update of the Map of Singular Scientific and Technical Infrastructures, the ICTS Map for 2021-2024, was approved.

The ICTS are facilities dedicated to cutting-edge research of the highest quality, as well as to the transmission, exchange and preservation of knowledge, technology transfer and the promotion of innovation.

The map has 29 ICTS distributed among all the territories, includes NANBIOSIS, the Infraestructure for Production and Characterization of Nanomaterials, Biomaterials and Systems in Nanomedicine with its 26 units.

As a novelty, the update incorporates four new nodes or infrastructures associated with the ICTS. Specifically, the NASERTIC computing node in Navarra, the CIEMAT computing node in Extremadura and Madrid, and the Port d’Informació Científica data node in Catalonia are incorporated into the ICTS Red Española de Supercomputación, while the Center for Microanalysis of Materials is associated as a node to the new distributed Infrastructure of Applications Based on Accelerators. Likewise, Navarra incorporates an infrastructure to this map for the first time, an instrument that improves the management of ICTS and helps these organizations to access funding from the Ministry as well as regional and European funds, particularly the ERDF funds and the Recovery Funds and Resilience (MRR).

In this sense, the minister announced that the next call to strengthen the ICTS, scheduled for the first half of 2022, will allocate 38 million euros until 2025 to finance lines of investment associated with the construction, development, instrumentation, equipment and improvement of its scientific- techniques. The previous call, published in 2021, dedicated nearly 37 million euros to these infrastructures.

NANBIOSIS is one of the five ICTS in the area of health sciences and biotechnology. This thematic area has significantly increased its representation in the current ICTS Map. Under the concept of distributed ICTS, infrastructure networks have been established in the field of imaging, nanotechnology and omics sciences. In addition, the high biological safety laboratories are also reinforced, expanding the infrastructures of this type that offer their services.

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The coming revolution: synthetic DNA and RNA for therapeutic and diagnostic applications

The discovery of the mRNA vaccines for the treatment of coronavirus, as well as new medicines for the treatment of genetic diseases, has been important in the quest of solutions for undrugable diseases in an unexpected short-time.

Thus, the chemical modifications of nucleic acids with diagnostic and therapeutic purposes is now a reality, a revolution that promises to give hopes on unsolved medical problems or optimize previous approaches, largely due to the research push for the development of mRNA vaccines against SARS-CoV-2 infection.

Now, the prestigious “The Chemical Record” journal has invited the Nucleic Acids Chemistry group, of IQAC-CSIC and CIBER-BBN and belonging to the Global Health Platform of CSIC, to describe the advances and modificacions of the nucleic acids in the last decade. The article, authored by Dr. Carme Fàbrega, Dr. Anna Aviñó and Dr. Ramon Eritja (coordinator and director, respectively, of Unit 29 of ICTS NANBIOSIS), reports the development of synthetic DNA and RNA for therapeutic and diagnostic applications.

The article describes the most important results from the Nucleic Acid Chemistry group in this area covering the international context that surrounded these studies. These include the development of modifications in potentially therapeutic oligonucleotides to enhance nuclease resistance as well as improving cellular uptake and avoiding side effects, and the advances in the use of DNA nanostructures in the controlled deposition of matter in surfaces and their potential application as drug delivery systems is reported.

Moreover, the article has been selected to illustrate the front cover of The Chemical Record, a journal of the Chemical Society in Japan, with a suggestive image that shows the research activity in this area. The back image is the three dimensional reconstruction of a DNA array described by the group of Dr. Seeman obtained by A. Garibotti in Barcelona. On the top the crystal structure of the Argonaute protein from the Protein Data Bank is shown. This protein is a natural player that helps the therapeutic action of RNA molecules.

Read the full article in this link.

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Experimental & molecular medicine: a new article with NANBIOSIS U17

ICTS-NANBIOSIS. UNIT 17 CONFOCAL MICROSCOPY SERVICE. (CIBER-BNN. UNIVERSITY OF ALCALÁ)

The UAH research groupTranslational research of chronic diseases associated with aging and kidney disease has recently published an article in which unit NANBIOSIS unit 17 and Leica SP5 confocal microscope has had a great contribution

Located in the Support Center for Research in Medicine and Biology, Faculty of Medicine and Healthe Sciences, University of Alcalá (UAH). The Unit is equipped with a Leica TCS-SP5 confocal microscope. The confocal module is equipped with three spectral detection channels, AOBS (Acousto-optical beam splitter) and a resonant scanner system that allows analysis at high speed and resolution and makes possible the analysis of dynamic in vivo physiological processes in short periods, significantly improving the survival of living biological samples by shortening the exposure times to lasers. Includes an argon laser, a He/Ne laser, a DPSS laser diode and a violet excitation laser. The microscope is coupled to a cell incubation kit that allows multi-position time-lapse experiments. The equipment includes a workstation and four software for acquisition and analysis, which allow 3D visualizations, co-location studies, FRAP (Fluorescent Recovery after Photo-bleaching), FLIP (Fluorescent Loss in Photobleaching) and FRET (Fluorescence Resonant Energy Transfer). The equipment allows 3D characterization in detail of living cells and tissues through the use of different fluorochromes, expression and localization of molecules in 2/3D, colocalization and interaction of proteins or other types of molecules; endocytosis and intracellular transport, in situ hybridization with fluorescent probes, interaction studies between cells and materials, etc.

The unit provides researchers with a wide array of routine and specialized services as well as the latest advances in microscopy, including technical and scientific support to scientists for the study of cell/tissue biology, physiology and pathogenesis of diseases.

Article of reference

Campillo, S., Bohorquez, L., Gutiérrez-Calabrés, E., García-Ayuso, D., Miguel, V., Griera, M., Calle, Y., de Frutos, S., Rodríguez-Puyol, M., Rodríguez-Puyol, D., & Calleros, L. Indoxyl sulfate- and P-cresol-induced monocyte adhesion and migration is mediated by integrin-linked kinase-dependent podosome formation Experimental & molecular medicine, 2022, 54(3): 226–238. https://doi.org/10.1038/s12276-022-00738-8

Abstract

Cardiovascular disease is an important cause of death in patients with chronic kidney disease (CKD). Protein-bound uremic toxins, such as p-cresyl and indoxyl sulfate (IS), are poorly removed during hemodialysis, leading to vascular endothelial dysfunction and leukocyte extravasation. These processes can be related to dynamic adhesion structures called podosomes. Several studies have indicated the role of integrin-linked kinase (ILK) in the accumulation of integrin-associated proteins in podosomes. Here, we investigated the involvement of ILK and podosome formation in the adhesion and extravasation of monocytes under p-cresol (pc) and IS exposure. Incubation of THP-1 human monocyte cells with these toxins upregulated ILK kinase activity. Together, both toxins increased cell adhesion, podosome formation, extracellular matrix degradation, and migration of THP-1 cells, whereas ILK depletion with speciﬁc small interfering RNAs suppressed these processes. Interestingly, F-actin colocalized with cortactin in podosome cores, while ILK was colocalized in podosome rings under toxin stimulation. Podosome Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP) and AKT protein depletion demonstrated that monocyte adhesion depends on podosome formation and that the ILK/AKT signaling pathway is involved in these processes. Ex vivo experiments showed that both toxins induced adhesion and podosome formation in leukocytes from wild-type mice, whereas these effects were not observed in leukocytes of conditional ILK-knockdown animals. In summary, under pc and IS stimulation, monocytes increase podosome formation and transmigratory capacity through an ILK/AKT signaling pathway-dependent mechanism, which could lead to vascular injury. Therefore, ILK could be a potential therapeutic target for the treatment of vascular damage associated with CKD.

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