Unidad de Investigación

• Four Catalan institutions are also participating in this project to develop molecules with coronavirus-neutralizing properties

The Supera COVID-19 Fund launched by Banco Santander through Santander Universities, in collaboration with Crue Spanish Universities and the Spanish National Research Council (CSIC), has granted €160,000 in funding to a research project on COVID-19 designed by a consortium made up of Navarrabiomed researchers and four Catalan institutions coordinated by the Universidad Pública de Navarra (UPNA). This project seeks to develop molecules with SARS-CoV-2-neutralizing properties for the treatment of patients requiring hospitalization and clinical supervision due to the infection’s severity.

These molecules are based on peptides specific to the ACE2 receptor that can reduce or halt the ability of SARS-CoV-2 to cause infection. “These molecules reproduce the human receptor region the virus attaches to,” explained project leader Jacinto López Sagaseta, from the Protein Crystallography Unit at the Navarrabiomed Biomedical Research Center. “We are trying to create molecules from this region that have a greater capacity to bind to the viral particle, which would hinder the virus’s ability to attach to the natural receptor and thus slow down infection.” According to López, these molecules may “help chemists design drugs that can mitigate the process and speed of infection and thereby facilitate patients’ clinical recovery”.

In order to implement the 12-month project, a consortium was set up of researchers from different disciplines, including chemical synthesis, protein engineering, structural analysis and cell biology, as well as specialists in the conditions of biosafety level three (BSL3, for laboratories, on a scale of one to four), to test the potential of these molecules. Specifically, besides Navarrabiomed and the UPNA, four Barcelona research institutions are also participating in the project: IRB Barcelona (Institute for Research in Biomedicine), IQAC-CSIC (Institute for Advanced Chemistry of Catalonia), CIBER-BBN (Bioengineering, Biomaterials and Nanomedicine Subject Area of the CIBER Biomedical Research Center), and IRTA (Institute of Agrifood Research and Technology). Besides Jacinto López Sagaseta, other Navarrabiomed researchers taking part in this research project include Gilda Dichiara Rodríguez, Elena Erausquin Arrondo and Ane Ochoa Echevarría, who are members of the Protein Crystallography Unit.
The consortium members hope that “the availability of molecules with a strong inhibitory effect will significantly mitigate the socioeconomic impact of the pandemic due to the persistence of current and/or future SARS-CoV-2 outbreaks, as well as outbreaks of other potentially harmful coronaviruses with similar entry routes,” said López.

€8.5 million fund

The €8.5 million Supera COVID-19 Fund has been earmarked for projects of different organizations that are based on the fund’s three-pronged strategic approach against COVID-19: research on the virus and its prevention, research on its social impact, and strengthening universities’ technological capacity and reducing the digital divide. A total of 700 grant applications were submitted, of which 35 were selected and received funding to the tune of €5 million to carry out applied research against the virus. Nearly €1 million was also distributed to twelve projects on the social impact of the virus. Finally, €2.5 million will be allocated to supply young university students in unfavorable socioeconomic situations throughout Spain with nearly 5,000 computers and 15,000 Internet connectivity solutions and webcams.

• The Government of Navarre provided €1.1 million in funding for eight research projects and has now added two more Navarre initiatives to the list of recipients of funding from the Carlos III Health Institute

María Chivite, the President of the Government of Navarre, recognized “the good work” being done at research centers and institutes in the Region of Navarre to find alternatives that help alleviate the effects of COVID-19. She spoke in the context of a meeting she attended this morning with ten researchers in charge of their own publicly funded studies on this disease, which has caused 515 deaths in Navarre and more than 27,000 in all of Spain.

The meeting was also attended by Santos Induráin, the Minister of Health, and Juan Cruz Cigudosa, the Minister of University, Innovation and Digital Transformation, and provided a firsthand opportunity to learn about the research purpose of the projects that have received grants from the Navarre COVI+D Fund. Created by the Government of Navarre to promote research on this topic, the fund paid out €1.1 million in May to eight projects that had received a favorable assessment from the Carlos III Health Institute. The Carlos III Health Institute has also provided direct funding of €232,000 for two other Navarre research projects.

Chivite took advantage of the forum to remind the participants of the Government of Navarre’s commitment to innovation and research “as a model of economic and social development,” not just through these grants, but also by means of the R&D&i Emergency Plan, presented last week, and the Reactivate Navarre Plan / Nafarroa Suspertu 2020-2023. The Government is also committed to improving technological infrastructure and promoting supra-regional cooperation. “We want Navarre to lead the way in biomedicine because we have the talent and skills to do just that. It’s one of the strategic areas we’re working on. We have to be able to transfer knowledge and research to favor industrial and technological development,” she said, before expressing her confidence that Navarre will become “a key stop on the R&D&i map.”

Chivite confirmed that the goal of the Government of Navarre is “to keep increasing investment and setting up strong pillars for the model of growth.” Navarre will thus be prepared for future challenges of the likes of COVID-19.

Chivite informed the researchers of the public support of their research work, though “people are aware of the pressure you’re under when you’re studying this coronavirus, because of the high expectations about finding a vaccine, treatments and other aspects that could alleviate the effects of a virus that has had a major impact on our society.” She asked for respect “for the time frames, rigor and meticulousness” of the researcher’s work, and also expressed hope that this work would promote “true and instructive information” that avoids fake news and disinformation in society as a whole.
 

Ten projects

In addition to President Chivite, the meeting was attended by Rosario Martínez, the Director General for Innovation. Also attending were the researchers from the ten projects that received public funding: Luis Martínez de Morentin, Fermín Mallor Giménez, Borja Sáez Ochoa, Natalia Ramírez Huerto, Jacinto López Sagaseta, Pablo Sarobe Ugarriza, Patricia Fanlo Mateo, David Escors Murugarren, Jesús Castilla Catalán and Leyre Ruete Ibarrola, who attended in representation of Beatriz Lacruz Escalada. They were joined by the heads of the different research centers where the projects are being carried out. This group included María Rosario Luquin, the Scientific Director of  the Navarre Health Research Institute (IdiSNA), Claudio Fernández, the Director of the Lurederra Foundation, and Íñigo Lasa Uzcudun, the Director of Navarrabiomed.

The directors of the ten research projects presented their lines of research, which include the study of possible vaccines, the use of specific drugs, resource management, the development of preventive measures and products, and the analysis of incidence bearing in mind sociodemographic characteristics and other conditioning factors.

The Government of Navarre aims to promote Navarre innovation and national prominence through the COVI+D Fund grants. But the goal is also to attract scientific talent, given the fact that these grants include staff payroll expenses.

The Microbial Pathogenesis Unit of Navarrabiomed-Public University of Navarra (UPNA) has found a new genetic organisation in bacteria that helps better understand bacterial biology. The study of this genetic architecture was published in Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Research background

In 1961, François Jacob and Jacques Monod discovered that bacteria group the genes that encode the proteins for a certain metabolic pathway in a single transcription unit (which they called ‘operon’). They won the Nobel Prize in Physiology or Medicine in 1965 for their discovery.

The bacteria they chose for their study was Escherichia coli, which normally lives in the intestines of healthy people; specifically, they studied the set of genes E. coli bacteria need to transport lactose (milk sugar) and break it down. E. coli only produces the three proteins it needs to digest lactose when the sugar is available. To simplify transcription regulation, the three genes involved are adjacent in the genome and under a single regulation system. Similar transcriptional regulation systems are found in other metabolic pathways in all bacteria.

Research at Navarrabiomed

In 2018, the team of researchers at Navarrabiomed coordinated by Iñigo Lasa Uzcudun, Head of the Microbial Pathogenesis Unit and Director of the biomedical research centre, described a new way genes are organised in bacteria. This regulation system has a higher level of regulation in operon structure, which the authors of the study named ‘non-contiguous operon’.

The bacterial model analysed has a group of four genes that are transcribed as a transcription unit despite the existence of a separate gene between the second and third genes that is transcribed in the opposite direction.

This transcriptional architecture results in an antisense transcript that acts as a mutual regulation system for the expression of the genes in the operon and the gene that produces this antisense transcript. Therefore, the concept of non-contiguous operon includes not only the genes transcribed from the same transcription unit but also overlapping genes whose expression is coordinated with that of the genes in the operon.

This finding deepens the understanding of bacterial biology and may trigger novel developments in the fields of synthetic biology and bacterial biotechnology.
The study was carried out as part of the scientific activity done at the Navarra Medical Research Institute (IdiSNA).

• Paper published in PNAS.

• El estudio, financiado por el Ministerio de Economía, ha sido publicado por la prestigiosa revista Nature Communication.

Un equipo científico del centro de investigación biomédica Navarrabiomed -centro mixto del Gobierno de Navarra y la Universidad Pública de Navarra (UPNA)- ha conseguido caracterizar el sistema sensorial que las bacterias utilizan entre otras cosas para multiplicarse en el cuerpo humano y causar infección.

El avance, que ha sido publicado por la revista científica Nature Communications y cuenta con financiación del Ministerio de Economía, Industria y Competitividad, permite comprender mejor cómo las bacterias se adaptan a las diferentes condiciones ambientales y posibilitará el desarrollo de antibióticos más específicos y eficaces.
El estudio ha contado con el liderazgo del doctor Iñigo Lasa, director de Navarrabiomed e investigador responsable del Grupo de Patogénesis Microbiana del centro. Asimismo, han colaborado investigadores del Instituto de Agrobiotecnología (UPNA-CSIC-Gobierno de Navarra), del Instituto de Biomedicina de Valencia (CSIC) y del Institute of Infection, Immunity and Inflammation, University of Glasgow.

Bacterias superresistentes

Actualmente, la aparición de bacterias farmacorresistentes, que no responden a tratamientos con antibióticos, constituye uno de los problemas sanitarios a escala mundial priorizados por la Organización Mundial de la Salud (OMS).

Las bacterias detectan, responden y se adaptan a los cambios en su entorno utilizando unos elementos sensoriales denominados sistemas de dos componentes. Este tipo de sistemas sensoriales están presentes en bacterias, hongos y plantas, pero no se encuentran en células animales. En el caso de las bacterias, regulan procesos celulares tan importantes como la virulencia o su propio crecimiento, lo que los convierte en dianas para el diseño de nuevas terapias antimicrobianas.

El objetivo del trabajo ha consistido en eliminar todos los sistemas de dos componentes, es decir el sistema sensorial completo, en Staphylococcus aureus, uno de los principales patógenos humanos según la OMS y, posteriormente, en la generación de una colección de bacterias cada una de las cuales contiene un único sistema de dos-componentes. Esta estrategia ha permitido simplificar una compleja red sensorial en cada uno de sus elementos para comprender cuál es la función individual de cada uno de los sistemas y la relación existente entre ellos. 

Aplicación clínica de la investigación

En relación a la aplicación clínica, Iñigo Lasa apunta al desarrollo de nuevos antibióticos más específicos. “El hecho de que los sistemas de dos componentes estén presentes en todas las bacterias patógenas y no en las células de nuestro organismo nos puede permitir desarrollar fármacos que bloqueen estos sistemas, evitando así el desarrollo de la bacteria durante la infección, sin causar ningún efecto secundario sobre nuestras células”.

En este sentido, las bacterias generadas en este estudio han sido patentadas y actualmente el equipo analiza diversos compuestos marinos que puedan incorporarse en el tratamiento y control de infecciones en la práctica clínica.

La investigación forma parte de la actividad científica del Instituto de Investigación Sanitaria de Navarra (IdiSNA), agrupación público-privada para el fomento de la investigación biomédica en la Comunidad Foral y de la que son miembros Navarrabiomed y la UPNA.

• Información adicional sobre el paper: Behind the paper - Nature Microbiology: "Life without sensing. Can Staphylococcus aureus live without two-component sensorial system?"

High-cholesterol levels, or hypercholesterolemia, affects nearly 1500-2500 people in Navarra, and less than 20 per cent of them are not aware that they suffer from this condition. Hypercholesterolemia is considered to cause 22 per cent of coronary events, most of which could be prevented with early diagnosis and treatment. The biomedical research centre Navarrabiomed has launched NAGENCOL, a project to address this issue using whole-genome sequencing as a diagnostic tool to offer personalised treatment to patients who suffer from hypercholesterolemia. The project is framed within NAGEN, a global strategy aimed at applying genomic medicine in the Navarra Health System-Osasunbidea (SNS-O).

Currently, hypercholesterolemia poses a real challenge to the public health system, because the life expectancy of untreated patients can decrease by 25 years, and 50 per cent of them are more likely to have a heart attack before the age of 55. NAGENCOL addresses this problem, offering a new model that uses genomic information, together with other clinical and demographic data, to bring precision medicine to individual patients.

This ambitious public health project has a budget of 2 million Euro, contributed by the Department of Economic Development at the Directorate-General for Industry, Energy and Innovation of the Government of Navarra, within the framework of the Genomics and Advanced Medicine project (GEMA) and the Intelligent Specialisation Strategy S3.

The NAGENCOL activities are managed by five strategic partners specialising in clinical practice, scientific and technical services, and research. They include the Navarra Hospital Complex (CHN), Nasertic, Tracasa Instrumental SL and Navarrabiomed as the leader of the study. The project is headed by Dr Ander Ernaga and Dr Juan Pablo Martínez from the Endocrinology Service at CHN.

NAGEN Strategy

Since 2016, Navarrabiomed has been leading the Genomic Medicine Strategy (NAGEN) of the Navarra Health System-Osasunbidea. With the support of the Government of Navarra, Navarrabiomed has since coordinated two strategic projects: NAGEN 1000 (best precision medicine project award winner in 2018) and Pharmanagen.

The two initiatives, along with NAGENCOL, are being used to set up, in the SNS-O patient care units, the infrastructure required for using genomic data as a powerful diagnostic tool and to determine the best personalised treatment for each patient.

Navarrabiomed has led the NAGEN: Navarra Genome 1000 project since 2016. The project focuses on whole genome sequencing for a new approach to rare genetic disorders in the Navarra Health System-Osasunbidea (SNS-O). So far, thanks to collaboration with doctors from 18 medical specialties at the Navarra Hospital Complex (CHN), the study includes data about 400 patients and their relatives, precise diagnoses for 25 per cent patients and identification of possible causes for another 25 per cent.

The patients that are part of the study had not been accurately diagnosed, despite having been treated by several specialists and having taken a large number of traditional tests. Angel Alonso, the coordinator of the project, highlighted the project’s relevance to healthcare services: ‘Making genomic analysis available to the public health system is revolutionary. It means a significant change in the clinical approach to patients with rare genetic disorders.’

Impact on the patient and their family

On the occasion of Rare Disease Day on the last day of February, it is worth mentioning that about 6 per cent of the global population are individuals with rare diseases. In Navarra, their number amounts to 38,000. At present, there are 7000 types of rare diseases, most of them of genetic origin.

In many cases, genetic testing enables the patient and their family to get a deeper knowledge of their condition and its progression, to understand how a genetic disease is inherited and to learn about the risks for other family members. The emotional significance of finding answers to the questions posed by the symptoms – which sometimes have remained unanswered for too long – means putting an end to uncertainty and isolation for most patients with rare diseases.

NAGEN 1000: a pioneering project in Spain

NAGEN 1000 is a ground-breaking project at the national level, placing Navarra at the forefront of genomic analysis and technology. The project was introduced last year at the Senate Presentation of Genomic Studies, whose conclusions were approved in 2019, thus green-lighting the development of a national strategy for personalised medicine.

Currently, the project’s methods, procedures and infrastructure are being transferred to daily clinical practice in SNS-O, to the benefit of the people of Navarra.

NAGEN 1000 is financed by the Economic Development Department at the Directorate-General for Industry, Energy and Innovation within the framework of the Intelligent Specialisation Strategy S3. It is being developed by a consortium made of CHN, Nasertic (a company run by the Government of Navarra), Avantia and Navarrabiomed, leader and coordinator of the project, with the support of the Directorate-General for Information Technology, Telecommunications and Public Information (DIGITIP), and the cooperation of the Centro Nacional de Análisis Genómico (CNAG-CRG) and the Clinical Bioinformatics Research Area into Rare Diseases (CIBERER) of Instituto de Salud Carlos III (ISCIII).

• The programme will offer support to the development of studies in digestive medicine, geriatrics, neuroscience and oncology that will bring advancement and excellence in these fields of research.
• ‘la Caixa’ Foundation and Caja Navarra Foundation are channelling 1.2 million Euro into this programme, to be run by the biomedical research centre Navarrabiomed, where four doctors from the Navarra Health System-Osasunbidea (SNS-O) will carry out quality biomedical research studies.
• Through this programme, ‘la Caixa’ Foundation and Caja Navarra Foundation will give support to the leading research centres in Navarra during the 2017-2021 period. Universities and research centres will thus get a total 6.4 million Euro.

Ana Díez Fontana, Regional Director of CaixaBank in Navarra; Javier Miranda, Chairman of Caja Navarra Foundation; and Iñigo Lasa, Director of Navarrabiomed, announced the research lines to be developed by doctors Eduardo Albéniz Arbizu, Nicolás Martínez Velilla, Maite Mendióroz Iriarte and Antonio Viudez Berral, who were selected by an external evaluation committee from 12 candidates.

The specialists in the programme will be relieved from part of their medical activity so that they can do research. They need time to develop their scientific projects and produce new knowledge in their medical specialties. The initiative enables the establishment of a critical mass of professionals that combine medical activity with research jobs, thus promoting translational medicine to the benefit of patients and society as a whole.

The four doctors selected to join the programme will soon start working at the labs of Navarrabiomed – the joint biomedical research centre of the Government of Navarra and the Public University of Navarra (UPNA). They will establish separate research units for the development of their projects, based on clinical practice at the Navarra Hospital Complex (CHN), with support from other Navarrabiomed units and platforms.

In addition to streamlining research activities in the respective units, they will encourage the participation of resident medical interns (MIRs) by getting them involved in biomedical research projects, trials and programmes.

Four excellent research projects in digestive medicine, geriatrics, neuroscience and oncology

Eduardo Albéniz Arbizu has worked in a number of hospitals across Spain. He received training in advanced endoscopy in France, Japan and China. Currently, he is working at the Gastrointestinal Endoscopy Unit of the CHN Digestive Medicine Service.

Dr Albéniz specialises in endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for the removal of early-stage gastrointestinal tumours. These advanced procedures reduce the number of surgical and other more invasive interventions in the treatment of superficial neoplastic lesions. Resection of colorectal polyps, for example, is the procedure with the highest survival rates observed in screening studies for colorectal cancer carried out in Navarra.
The goal of the project led by Dr Albéniz is to provide evidence for the identification of predicting factors for the effectiveness of resection procedures and other factors associated with potential complications that might be minimised.

Nicolás Martínez Velilla has been the Head of the Geriatrics Unit at CHN since 2015. In 2013, he was appointed head of a team partnered with Navarrabiomed for the promotion of research into different aspects of geriatric medicine.

Dr Martínez Velilla’s proposal includes a thorough study for the prevention of old-age frailty and disability or dependency in hospitals and in the community at large. Furthermore, it includes the creation of a European cross-border network to deal with various aspects of ageing. The project is aimed at rethinking hospitalisation of older adults, prescribing exercise to older patients in hospitals so as to improve their quality of life and increasing the sustainability of the health system.

Maite Mendióroz Iriarte has built her professional career as a doctor and researcher in Pamplona, Barcelona, San Sebastián and New York. Since 2010, she has been a member of the Neurology Department at CHN. Over the past few years, she has received grants from ‘la Caixa’ Foundation, Caja Navarra Foundation and the Government of Navarra to boost activity in the Neuroepigenetics Unit at Navarrabiomed.

Between 2018 and 2021, Mendióroz Iriarte will develop a project whose goal is to identify a potential blood-based epigenetic biomarker for early detection and treatment of Alzheimer’s disease. Her study might become the first step towards the implementation of precision medicine in neurodegenerative diseases.

Antonio Viudez Berral has developed his professional career in Navarra, Catalonia and Baltimore, USA. In 2010, he joined the Medical Oncology Service at CHN. Since then, he has been a researcher at Navarrabiomed as well.

Dr Viudez’s project will study pancreatic neuroendocrine tumours to find accurate markers that predict the effectiveness of certain therapies.

In addition, the Medical Oncology Service will be able to strengthen its scientific activity, establishing new lines of research for the improvement of diagnosis, prognosis and prediction of treatment response and toxicity.

From left to right: Luis Gabilondo, Ana Díez, Maite Mendióroz, Eduardo Albéniz, Antonio Viudez, Nicolás Martínez, Javier Miranda and Iñigo Lasa.

•    A consortium made of more than 600 professionals from 50 countries highlights the importance of confirming the diagnosis of people presenting with alterations in their capacity to smell and taste
 

Navarrabiomed is participating in an international research project that has confirmed that most people suffering from COVID-19 experience a loss of their sense of smell and/or taste. This initiative is part of an international consortium made up of more than 600 professionals from 50 countries.

Enrique Santamaría Martínez PhD, Head of the Navarrabiomed Clinical Neuroproteomics Unit, is responsible for leading the center’s participation in an international consortium that has confirmed the direct relationship between COVID-19 and anosmia (loss of the sense of smell) and the reduction in taste capacity in early stages of the disease. More than 600 professionals from 50 countries are collaborating on this study, whose findings may determine who is given diagnostic tests in new outbreaks.

On 7 April 2020, the Global Consortium for Chemosensory Research (GCCR) launched a massive survey with the aim of gathering sensory information on the ability to smell and taste of participants, people diagnosed with an objective test such as PCR or after clinical assessment no more than 15 days prior to responding to the survey. Among other variables, participants were asked to quantify their smell, taste and chemesthesis function (their capacity to smell, taste and perceive cooling, tingling and burning sensations in the mouth) before and while suffering from COVID-19 disease. They were also asked to mention any kind of nasal obstruction that had occurred.

The consortium obtained preliminary results 11 days later, on 18 April, and published the findings on 8 May in the free-access repository medrxiv.org. A total of 4,039 people from more than 40 countries filled out the survey and an analysis of the results indicates that smell, taste and chemesthesis were significantly reduced in patients diagnosed with COVID-19 disease. It is important to point out that nasal obstruction does not seem to be associated with these losses, which suggests that it may be an indicator for differentiating infection from SARS-CoV-2 from other viral infections such as cold and flu (which do produce nasal obstruction).

The reduction in the capacity to smell and taste may be taken as a distinctive characteristic of possible cases of COVID-19 arriving at hospitals and health centers and that require confirmation by means of a diagnostic test.

The project is different from previous studies on chemosensory abilities and COVID-19 because it proposes a massive international approach within a collaborative open-science framework. The study is led by Valentina Parma (Temple University, Philadephia, USA), John Hayes (Penn State, USA), Thomas Hummel (Technische Universität Dresden, Alemania), Steve Munger (Universidad de Florida, USA) and Danielle Reed (Monell Chemical Senses Center, USA). 

Research in progress

The consortium has now received more than 37,000 responses and the survey is still active. Navarrabiomed encourages anyone who has recently suffered from a respiratory disease, including COVID-19, to go online to https://gcchemosensr.org/ and fill out the survey in one of the 29 languages available. “Patient participation is key for determining the symptomatology of SARS-CoV-2. Consortium committees are currently organizing specific research projects that will make use of all the information compiled in the GCCR initiative,” said Dr. Santamaría.

The Navarrabiomed Clinical Neuroproteomics Unit is interested in determining why COVID-19 patients lose their sense of smell. To answer this question, the Unit is collaborating with the group of Dr. David Escors (Head of the Oncoimmunology Unit, Navarrabiomed) in order to untangle the molecular mechanisms that are altered at the olfactory level by the SARS-CoV-2 virus.

“One of the coronavirus’s access routes is through the nasal cavity, which is why analysis of the “nose-brain” route could provide information on why strokes, seizures and encephalitis have been observed in some COVID-19 patients”.

Furthermore, according to preliminary results from the seroprevalence study carried out by the Spanish Ministry of Health and the Carlos III Health Institute, the loss of smell should not merely be considered an early symptom of COVID-19 disease, but also a predictor of immune response,” Dr. Santamaría said.

The Navarrabiomed Neuroproteomics Unit, in collaboration with public and private health institutions in Navarre, is currently working on the development and deployment of precision olfactory medicine, which, together with immunological analysis, will lead to more effective diagnosing and monitoring of the many diseases involving loss of smell, one of which is COVID-19.
 

LEnrique Santamaría and Joaquín Fernández-Irigoyen, researchers at the Proteomics Unit of the biomedical research centre Navarrabiomed, were the coordinators of Current Proteomic Approaches Applied to Brain Function, released by the academic publishing company Springer Nature as part of its Neuromethods collection.

The book introduces 20 standard protocols to deepen the knowledge of proteins and their role in neurodegenerative and psychiatric disorders.

In this book, Santamaría and Fernández-Irigoyen, who are also professionally related to the Navarra Medical Research Institute (IdiSNA) and the ProteoRed-ISCIII national platform, offer a compendium of methods for brain proteome quantification, post-translational modification monitoring, neuronal organelle identification and characterisation, and bioinformatics tool implementation for omics data integration. It is meant to be an essential guidebook for students a valuable resource for graduate students and postdoctoral fellows interested in neuroproteomics, as well as for researchers looking for further insight into the growing field of mass spectrometry in neuroscience.

Book contributors included as many as 75 researchers from labs in Spain, Switzerland, France, Denmark, Portugal, Germany, India, the USA and Brazil. Many of them are regular participants in The Human Brain Proteome Project (HBPP).

HBPP is an international initiative sponsored by the Human Proteome Organisation (HUPO) promoting proteomic studies on the human brain and follow-up projects to decipher the role of proteins in brain development, health and disease.

 

Saioa Mendaza Lainez, investigadora predoctoral en la Unidad de Patología Molecular del Cáncer de Navarrabiomed, realizará la lectura de su tesis doctoral por la Universidad Pública de Navarra el martes 30 de junio, a las 11:30, a través de videoconferencia en Navarrabiomed (solamente podrán acudir aquellas personas autorizadas previamente). 

La tesis, titulada Approaching the epigenome of triple-negative breast cancer to identify new biomarkers, ha sido desarrollada en Navarrabiomed bajo la dirección del Dr. David Guerrero Setas y la Dra. Esperanza Martín Sánchez.

El cáncer de mama es la neoplasia más frecuente en mujeres a nivel mundial y la primera causa de muerte por cáncer en este mismo sexo. La investigación aborda el cáncer de mama triple negativo (CMTN), un subtipo que a diferencia del resto carece de tratamiento dirigido, lo que conlleva consecuencias más agresivas en las personas que lo padecen. Esto hace que a día de hoy, la búsqueda de nuevos biomarcadores y dianas terapéuticas para esta enfermedad sea imprescindible.

Dado que las alteraciones epigenéticas están involucradas en la tumorigénesis, el objetivo de esta tesis ha sido caracterizar la metilación del DNA y la acetilación de histonas de este tipo de cáncer. Con ello se ha buscado identificar nuevas firmas potencialmente diagnósticas y pronósticas, así como alteraciones destinatarias de fármacos dirigidos.

Los resultados de esta caracterización han permitido concluir que el patrón epigenético está alterado en CMTN respecto a tejido mamario no neoplásico. Más importante aún, la investigación ha desvelado dos alteraciones epigenéticas específicas como potenciales biomarcadores de peor pronóstico: la acetilación de la histona H4K5 y la hipometilación del gen ADAM12, el cual se presenta también como posible diana terapéutica frente a este cáncer.

Asimismo, se ha identificado una nueva firma basada en metilación de DNA con utilidad diagnóstica. Por último, se han descrito los procesos biológicos de los distintos genes regulados por la acetilación de H4K6 en líneas celulares no neoplásicas y CMTN.

El trabajo realizado ha dado lugar a tres publicaciones científicas y ha sido difundido en dos congresos consecutivos de European Association for Cancer Research; uno celebrado en Manchester en el año 2017 y en Amsterdam en el 2018.

Para el desarrollo de la tesis Saioa Mendaza ha sido beneficiaria de dos becas: Ayudas para la formación de Personal Investigador de la Univesidad Pública de Navarra  para la realización de tesis doctorales y Beca a la excelencia de la Funcación Caja Navarra para la realización de una estancia en University of Massachussets Medical School (EEUU).

• Since 2015 the associations annual investment in research has been increased by 65%

On October 27th, 2019 Breast Cancer Association of Navarre SARAY collected 75,000 euros in the solidarity race celebrated in Pamplona. 49,970 euros will fund two studies developed by Navarrabiomed on metastatic breast cancer.

One of the projects is focused on liquid biopsy in this type of cancer, and it is led by Natalia Ramírez Huerto, the head of the Hematological Oncology Unit of Navarrabiomed. SARAY´s contribution for the second year of the project development raises to 24,970 euros. Other study lead by Cancer Signaling Unit head Imanol Arozarena Martinicorena will receive 22,000 euros. His project aims to develop new adjuvant therapies to treat brain and bone metastases from these tumors. The additional funds will be donated to the Chronos Hope Project from Solti Foundation.

On the 25th of June SARAY decided to allocate the incomes in a face-to-face and online assembly among 725 associates (event delayed three months later due to the COVID-19 crisis). During the last years, the organization shows a strong commitment with biomedical research performed in Navarre. Therefore, it is relevant to highlight that since 2015 SARAY has increased by 65% its annual investment in oncology research.

Imanol Arozarena, senior researcher from the Cancer Signalling Unit at the Navarrabiomed biomedical research centre and a member of Instituto de Investigación Sanitaria de Navarra (IdiSNA), has recently published a melanoma review with University of Manchester Professor Claudia Wellbrock.

The two scientists were asked by the renowned scientific journal Nature Reviews: Cancer to write an article on the latest findings in melanoma cell distinct phenotypes and their relevance for melanoma development and response to therapy.

As many as 4000 new melanoma cases are diagnosed in Spain every year. Malignant melanoma is a serious type of skin cancer that is usually metastatic. It is notorious for its intra- and inter-tumour heterogeneity.

Such variability results from the ability of melanoma cells (melanocytes) to adjust to changing environmental conditions by reprogramming their genetic expression. Thus, melanocytes develop resistance to both targeted therapy and immunotherapy, and their plasticity plays a role in metastasis development.

In their article, the authors reveal the importance of combining recent developments in genomic technologies and the availability of large gene expression datasets for a precise definition of the gene signatures that characterise changes in each patient’s tumours and the prognostic relevance for tumour development and response to therapy.

According to Arozarena, ‘By understanding the molecular mechanisms that adapt melanoma cells to anti-tumour drugs, we will be able to prevent both therapy resistance and the progression of metastatic melanoma.

• www.navarra.es
• Review Article - Phenotype plasticity as enabler of melanoma progression and therapy resistance

• The Carlos III Health Institute finances two projects in Navarre through Spain's COVID-19 Fund and grants the full amount applied for in both cases. 

The Spanish Ministry of Science and Innovation, through the Carlos III Health Institute (ISCIII), has awarded €232,000 to develop two public research projects within the context of the Navarre Health Research Institute (IdiSNA). David Escors Murugarren, a researcher at Navarrabiomed, and Jesús Castilla Catalán, a researcher at the Institute of Public and Occupational Health of Navarre (ISPLN), have received 100% of the amounts they applied for from the COVID-19 Fund, a mechanism approved by Royal Decree-Law 8 of 17 March 2020 on urgent extraordinary measures for dealing with the economic and social impact of COVID-19.

David Escors, the principal investigator at the Navarrabiomed Oncoimmunology Research Unit, began his scientific career working on coronaviruses at the Spanish National Biotechnology Center (CNB-CSIC), along with researcher Luis Enjuanes. He then continued his work at University College London (UCL) by applying lentiviral vectors and gene therapy in immunotherapy. He is a coronavirus specialist and the positive evaluation received from the ISCIII will enable him to obtain the €115,000 he applied for to develop the project “Platforms for developing biosafe SARS-CoV-2 vaccines.”

The aim of the initiative is to develop a platform for engineering biosafe vaccines for the virus that causes COVID-19 disease. The focus will be on the expression of viral proteins that may activate immunity. This line of research was started up specifically for COVID-19, given the current health emergency, but is based on the European ISOLDA Project - Horizon 2020 for generating more effective and safer virus vaccines (yellow fever, influenza and coronavirus) for adults over 65. Navarrabiomed has worked on this project since 2019 in coordination with professionals from the Spanish National Research Council (CSIC) and with Dutch, German and Italian collaborators.

Institute of Public and Occupational Health of Navarre

At the Institute of Public and Occupational Health of Navarre’s Group of Infectious Diseases and Vaccines, Jesús Castilla will lead the study “Infection, Hospitalization, ICU Admissions and Deaths Caused by SARS-CoV-2 in a Population Cohort.” To carry out the study, he will also receive the total amount applied for from the ISCIII: €117,000.

His proposal focuses on estimating the effect of sociodemographic characteristics, chronic diseases and other conditioning health factors on the risk of infection, hospitalization and severe forms of COVID-19. This will involve calculating the incidence of suspected cases, infections confirmed using PCR, hospitalizations, ICU admissions, assisted ventilation and mortality. The mortality rate will also be calculated in confirmed cases and hospitalizations. Antibody seroprevalence will also be evaluated in a sample of patients from the sentinel physician network and/or donors.

This is the second SARS-CoV-2 initiative for Jesús Castilla, given the ISPLN’s participation in the European project I-MOVE-COVID-19, with the involvement of 11 countries and 20 organizations. It is one of the European projects funded through the fast-track call of Horizon 2020, the European Union’s research and innovation program to promote research of different aspects of the SARS-CoV-2 virus.

Both research projects financed by the ISCIII will form part of the scientific activity of the IdiSNA, a public-private partnership for promoting biomedical research in Navarre. Both the ISPLN and Navarrabiomed are partnership members.

El Dr. Hugo Arasanz, oncólogo del Complejo Hospitalario de Navarra e investigador de la Unidad de Inmunomodulación de Navarrabiomed - IdiSNA, recibió ayer en Madrid la Ayuda Clínico Junior de la Asociación Española Contra el Cáncer (AECC). La financiación recibida (120.000 €) se destinará al proyecto "Subpoblaciones linfocitarias como biomarcador predictivo de respuesta a inmunoterapia anti-PD1/PDL1 en carcinoma no-microcítico de pulmón avanzado en 1º línea de tratamiento". Este estudio se desarrollará durante los próximos cuatro años y contará con la dirección del Dr. David Escors. 

El Museo Reina Sofía acogió ayer la entrega de las ayudas anuales de la AECC, dentro de los actos programados en el Día Mundial de la Investigación en Cáncer (WCRD en sus siglas en inglés), que se comemora cada año el 24 de septiembre. En total, la AECC ha entregado casi 21 millones de euros para financiar 171 proyectos que se suman a los 56M€ con los que hoy se están financiando 380 proyectos de investigación en desarrollo.

Asimismo, la asociación ha puesto de manifiesto la necesidad de elaborar un Plan Nacional de Investigación en Cáncer para alcanzar el 70% de supervivencia media a cinco años en el año 2030, en la actualidad se sitúa en un 53%.

Más información sobre el proyecto

La inmunoterapia antiPD1/PDL1 ha supuesto una revolución en el tratamiento del cáncer no-microcítico de pulmón, ya que ha mejorado los resultados de la quimioterapia, asociando además menor toxicidad. Por desgracia la proporción de pacientes que responden al tratamiento es reducida, son menos todavía los que mantienen la enfermedad controlada durante un periodo de tiempo prolongado, y no se dispone de biomarcadores predictivos que permitan identificar a estos pacientes con precisión.

El equipo del Dr. David Escors ha desarrollado un sistema de monitorización de poblaciones linfocitarias por citometría de flujo a partir de sangre periférica en pacientes en progresión a quimioterapia que permite predecir aquellos que van a responder a la inmunoterapia. Dada la reciente aprobación de la inmunoterapia en pacientes en primera línea, este proyecto pretende correlacionar los perfiles linfocitarios de los pacientes y su dinámica con la eficacia del tratamiento en este contexto, incorporando además el estudio de las citosinas proinmunogénicas en plasma y la posible influencia del daño genotóxico en las células inmunitarias producido por las diferentes terapias como causa de menor eficacia en segunda línea.

El proyecto del Dr. Hugo Arasanz se completará con estudios mecanísticos in vitro que permitan conocer los elementos que condicionan la respuesta al tratamiento y plantear combinaciones que puedan revertir la resistencia primaria a estas terapias.