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DEVELOPMENT AND INNOVATION IN ANIMAL HEALTH

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Directorio de grupos de investigación en Sanidad Animal

Líneas de Investigación

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Diseases of the circulatory system

Diseases of the circulatory system are conditions that affect the heart or blood vessels. These diseases are the leading cause of death worldwide, responsible for 17.5 million deaths annually. Among the main circulatory system diseases are atherosclerosis, stroke, cardiac fibrosis, myocardial infarction, and arrhythmias, among others. To investigate these diseases, cellular and animal models are used to study the underlying mechanisms and test new therapies. These models are essential for understanding how these diseases develop and progress, as well as for identifying potential treatments that can improve quality of life and reduce associated mortality. Research using these models has advanced significantly in recent decades, providing valuable insights that have contributed to the development of innovative drugs and medical techniques.

Cancer

Tumors originate from a mass of transformed cells that undergo abnormal growth and multiplication. Today, cancer, which refers to malignant tumors, is the second leading cause of death worldwide, with approximately 10 million deaths annually. Cancer research focuses on the study of animal and cellular models for a variety of tumor types, including adenocarcinomas, pancreatic, breast, colon tumors, lymphomas, leukemias, brain tumors, and metastasis. In addition, research investigates tumor and metastatic biomarkers, hematopoietic neoplasms, thyroid tumors, hereditary cancer, and thyroid cancer. These research models are crucial for understanding the biological mechanisms underlying cancer development and progression. They allow scientists to explore new therapies, identify biomarkers that can predict treatment response, and improve prevention and diagnostic strategies. The use of animal and cellular models has led to significant advances in oncology, providing a platform for drug discovery and the development of personalized treatments that can increase survival and improve the quality of life for cancer patients.

Respiratory system diseases

Chronic lung diseases affect one or more parts of the respiratory system, such as the bronchi, lungs, and chest cavity. Respiratory diseases are among the leading causes of death worldwide. In 2020, due to the COVID-19 pandemic, the death toll surged, and COVID-19 infection became the leading cause of death globally. Studies conducted by the National Statistics Institute reveal that respiratory diseases (such as pulmonary hypertension, COPD, cystic fibrosis, venous thromboembolism, and pulmonary edema) have significantly increased mortality rates in recent years. For example, in 2022, deaths from these diseases rose by 21% compared to 2021.

Nervous system diseases

Nervous system diseases encompass a wide range of conditions that can affect both the central and peripheral nervous systems. These diseases can significantly impact motor, sensory, and cognitive functions, affecting individuals’ ability to carry out daily activities and maintain an adequate quality of life. In the last decade, there has been a notable increase in the prevalence of these diseases, a trend closely linked to the rise in life expectancy and changes in lifestyle. The longer life expectancy of the aging population implies a higher incidence of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, which progressively affect memory, coordination, and other brain functions. Additionally, the modern lifestyle, characterized by an unbalanced diet, lack of physical exercise, and chronic stress, has contributed to an increase in neurological and peripheral disorders (neuropathies, amyotrophic lateral sclerosis, mental illnesses, epilepsy, etc.). These combined factors have led to a greater recognition of nervous system diseases as a critical public health concern, highlighting the need for more research, prevention, and treatment to mitigate their impact on the population. In recent years, the development of artificial intelligence and robotics has achieved significant advancements in the field of rehabilitation. The development of robotic devices, such as neuro-prostheses and robotic exoskeletons, is enabling major progress in therapies and rehabilitation for individuals with physical and neurological disabilities.

Digestive system diseases

Digestive system diseases encompass a variety of disorders that affect the functioning of the organs responsible for digestion and nutrient absorption. This system includes the mouth, esophagus, stomach, small intestine, large intestine, as well as accessory organs like the liver, gallbladder, and pancreas. These conditions can cause significant disruptions in digestion, nutrient absorption, and waste elimination, impacting an individual’s overall health. Common diseases include gastric ulcers, which affect the stomach lining, and inflammatory bowel diseases like Crohn’s disease and ulcerative colitis, which cause chronic inflammation of the intestines. Other relevant conditions include celiac disease, which involves gluten intolerance, type II diabetes, obesity, and liver diseases. In the past decade, there has been an increase in the incidence of some of these diseases, partly due to changes in dietary habits and lifestyles, such as increased consumption of processed foods and diets low in fiber. Additionally, factors such as stress and bacterial infections can contribute to the development of digestive disorders. The growing prevalence of these diseases highlights the importance of proper prevention, diagnosis, and treatment to improve both digestive and overall health in the population.

Infectious diseases

Infectious diseases are caused by external pathogenic agents such as viruses, bacteria, and other microbes. These agents enter the body, where they begin to multiply and spread. The disease develops when these microorganisms cause damage to the body’s cells and tissues, triggering an inflammatory response and a range of symptoms that affect the individual’s overall health. The interaction between the pathogen and the host’s immune system determines the severity and progression of the infection. Recent reports from the World Health Organization (WHO) rank infectious diseases among the top 10 causes of mortality in low-income countries. Among the most prevalent infectious diseases are AIDS (caused by the HIV virus), tuberculosis, and hepatitis B and C.

Immune system diseases

Immune system diseases, such as lupus, multiple sclerosis, and atopic dermatitis, are disorders that affect the body’s immune response, which is crucial for protecting against infections and diseases. These conditions may involve dysfunction in the activation and regulation of immune cells, like T lymphocytes. In autoimmune diseases, the immune system mistakenly attacks the body’s own cells, while in immunodeficiencies, the system is unable to mount an adequate response against pathogens. These dysfunctions can lead to increased susceptibility to infections, chronic diseases, and damage to healthy tissues, significantly impacting the individual’s health and well-being.

Rare diseases

Rare diseases are conditions that affect a small number of people compared to more common diseases. These conditions, often genetic, present varied and complex symptoms that can affect multiple systems in the body. Although each rare disease may have distinct characteristics, collectively they represent a significant challenge for diagnosis and treatment. It is estimated that there are more than 7,000 rare diseases, many of which have a severe impact on the quality of life and life expectancy of those affected. Some examples of these diseases include Hereditary Hemorrhagic Telangiectasia (HHT), Von Hippel-Lindau syndrome (VHL), propionic acidemia (PA), hyperphenylalaninemias, and syndromes such as Joubert (JBTS), Bardet-Biedl (BBS), Ellis-van Creveld (EvC), and Meckel-Gruber (MKS). To research these diseases, cellular and animal models are used to uncover the underlying mechanisms and explore potential therapies. These models are crucial for understanding the specific biology of each rare disease and for developing treatments that may alleviate symptoms and improve outcomes. Research in this field has advanced considerably in recent years, providing valuable insights that have led to the development of personalized therapies and innovative approaches to treat these conditions.

Pharmacokinetic and biodistribution

Pharmacokinetic and biodistribution studies are essential for understanding how a drug behaves in the body after administration. Pharmacokinetics focuses on the study of absorption, distribution, metabolism, and excretion of a drug, providing key information about the drug’s concentration in various tissues and bodily fluids over time. In contrast, biodistribution examines how a drug is distributed throughout the body and which organs or tissues it accumulates in, which is crucial for assessing its efficacy and safety. These studies are conducted using cellular and animal models to simulate how the drug disperses and metabolizes in a living organism. Research in pharmacokinetics and biodistribution allows for optimizing drug formulations, adjusting doses, and predicting potential adverse effects. In recent decades, advancements in analytical techniques and the development of experimental models have deepened our understanding of these processes, facilitating the design of more effective and safer therapies.

Design and formulation of new drugs

The design and formulation of new drugs is a crucial process in research aimed at creating innovative medications to treat various diseases. This process begins with designing molecules that can effectively interact with specific biological targets, followed by a formulation that ensures the drug’s stability, bioavailability, and efficacy. Scientists use advanced medicinal chemistry and biotechnology techniques to optimize the drug’s properties and ensure it is safe and effective for human use. Additionally, the formulation must take into account factors such as controlled release of the active ingredient and compatibility with other components of the medication. This comprehensive approach ensures that new drugs are not only innovative but also practical and safe for treating various health conditions.

Drug release

Drug release is the process by which an active ingredient is released from its formulation for absorption and therapeutic action. This process is critical for the drug’s efficacy and can be designed to release the drug in an immediate, controlled, sustained, or targeted manner. Drug delivery systems, such as polymeric matrices, liposomes, or microspheres, enable prolonged or localized release, optimizing bioavailability and minimizing side effects. The choice of the appropriate release system is based on the drug’s properties and the need to maintain effective therapeutic levels while reducing systemic toxicity.

Toxicological studies

Toxicological studies are essential for assessing the safety of a drug before it is approved for clinical use. These studies investigate the potential adverse effects of the active ingredient at various levels, from the whole organism to individual cells. They are conducted through various phases, including acute, subacute, and chronic toxicity studies, as well as evaluations of genotoxicity, carcinogenicity, and reproductive effects. Toxicological studies help identify and quantify potential risks, allowing for adjustments in dosage and formulations to minimize adverse effects. The information obtained is crucial for ensuring that the drug is safe for human administration and for meeting regulatory requirements.

Studies of physical, chemical, and biological composition of new drugs

Studies of the physical, chemical, and biological composition of new drugs are fundamental for ensuring the quality and efficacy of the medication. These studies analyze the drug’s physical properties, such as solubility, stability, and release profile, as well as its chemical composition to ensure purity and the absence of contaminants. Additionally, the biological properties of the drug are examined, including its interaction with biological targets and its behavior in biological systems. These analyses are essential for validating the consistency of the product, ensuring it meets specifications, and confirming that the drug acts effectively and safely in the body.

Microbiological evaluation studies

Microbiological evaluation studies are crucial for ensuring the safety and efficacy of pharmaceuticals by identifying and controlling potentially harmful microorganisms. These studies involve the detection, quantification, and characterization of microbial contaminants in drug products, as well as the assessment of the effectiveness of preservatives and sterilization methods. Rigorous testing is performed to verify the absence of pathogens and ensure that products meet established microbiological standards. Microbiological evaluation helps prevent infections and guarantees that the drug is safe for administration, minimizing the risk of contamination and preserving the integrity of the product.

Chemical stability studies of drugs or compounds

Chemical stability studies of drugs or compounds are crucial for ensuring that a medication maintains its efficacy and safety throughout its shelf life. These studies evaluate how the drug degrades under various environmental conditions, such as temperature, humidity, and light. Changes in the chemical composition of the drug are examined to identify potential degradation products that could affect its potency, safety, or quality. The data obtained help determine the drug’s expiration date, appropriate storage conditions, and the duration for which the drug remains within specifications. These studies are essential for ensuring that medications are safe and effective until the end of their shelf life.

Cytotoxic studies

Cytotoxic studies are essential for assessing the toxicity of new drugs or compounds at the cellular level. These studies analyze the effect of substances on cell viability and function, helping to identify potential damage or adverse effects that could compromise the safety of the medication. Tests are conducted to measure the drug’s ability to induce cell death, alter cell growth, or modify the behavior of cells in culture. These studies are crucial for ensuring that the drug does not cause significant toxicity in human or animal cells, thereby guaranteeing its safety before proceeding to more advanced clinical trials.

Confocal and Transmission Electron Microscopy Service at the Estacion Experimental del Zaidin. CSIC (CTEM)

The Confocal and Transmission Electron Microscopy is a newly-created Core Facility, conceived to fulfill the increasing demand of the researchers in this field. The service is initially aimed to organize, handle, optimize and promote the use of the large equipment of microscopy already available at the institute. The service is designed to ease the access of the EEZ researchers to these equipments, particularly for the observation of samples. Furthermore, standard preparation of samples prior to the observation will be also facilitated in some extent. The service will be available for both Internal and External users. Web link to CTEM: https://www.eez.csic.es/servicio-de-microscopia-confocal-y-electronica-de-transmision-de-la-estacion-experimental-del

Collaboration in Research Projects

- Support in biomarker studies: Participation as a partner in national or international research projects related to molecular biomarkers in prion, neurological, or infectious diseases. - Support in genetic studies: Participation as a partner or execution of proyects related with the identification of the genetic basis of diseases. Collaboration in microbiota studies: Design and execution of projects to analyze gut microbiota in relation to animal and human diseases.

Consultancy and Training

- Consultancy for animal health and One Health projects: Guidance on integrating interdisciplinary approaches in projects related to infectious diseases, microbiota, or neurodegenerative conditions. - Technical training: Courses and workshops on advanced genomic, transcriptomic, microbiota analysis, or molecular diagnostic techniques for students, researchers, or veterinary and biomedical professionals.

Microbiology and Molecular Epidemiology Services

- Molecular characterization of pathogens: Identification and analysis of microorganisms using techniques such as MLST, whole-genome sequencing, or antibiotic resistance gene profiling. - Molecular diagnosis of pathogens: Use of conserved sequences (16S-rRNA, ITS) to identify cryptic microorganisms responsible for animal pathologies.

Development of Biological Models

- Development of cellular models: Creation of in vitro models based on MSCs or iPSCs to study prion or neurological diseases. - Exosome characterization: Identification of biomarkers in exosomes for the early diagnosis of different diseases in domestic animals.

Diagnostic and Genetic Analysis Services

- Genotyping of genes associated with prion diseases: Identification of genetic variants in animals to assess susceptibility or resistance to prion diseases. - Genotyping of known mutations related to animal diseases with a genetic origin. - Genomic and transcriptomic sequencing: Identification of molecular biomarkers in various animal species using advanced technologies such as SNP arrays, RNA-seq, or exosome analysis. - Gut microbiota studies: Metagenomic analysis to evaluate the impact of microbiota on neurological and neurodegenerative diseases, such as canine idiopathic epilepsy or ovine scrapie.

Molecular diagnostic service for wildlife

Our group has numerous protocols to detect infectious agents of interest in wildlife using molecular biology techniques, such as Plasmodium spp., Haemoproteus spp., Toxoplasma gondii, fungal and bacterial agents, and viral agents (e.g., herpesvirus, adenovirus, poxvirus).

Health and Biotechnology

Specialized diagnosis: pathology - serology - microbiology - new genetic tools. New techniques for comprehensive hunting management. Integrated control of shared diseases. Biotechnology applied to livestock and hunting. Development and application of the latest technologies in integrated wildlife monitoring: censuses, health surveillance, etc. Identification of new antigens and vaccine development. Applications of proteomics, metabolomics and systems biology in the health field and in animal production. Development of new tools for diagnosing infections in wildlife. Population genetics and its application to the solution of health and management needs.

Veterinary pathological diagnosis service

Provision of services to the public administration, animal production companies, veterinary professionals, zoos and aquariums for the pathological diagnosis of diseases in different animal species. • Provision of services and scientific collaboration with companies and research centers / groups for the evaluation of the effects of diets / treatments / vaccines in animal species, as well as for the optimization of production protocols. • Advice to companies and research centers / groups in the evaluation of the health status and well-being of production and experimental animals (team members have training certificates in the protection of experimental animals).

Biological Alert Laboratory Network (RE-LAB)

INIA-CISA takes part of the Biological Alert Laboratory Network (RE-LAB), under the Presidency of the Government and dedicated to dealing with threats caused by biological agents. Coordinators INIA-CISA for RELAB: Miguel Angel Jiménez (majimenez@inia.es) y Alejandro Brun (brun@inia,es)

Network of High Biosafety Laboratories (RLASB)

The INIA-CISA, with IRTA-CReSA, belongs to the Network of High Biosafety Laboratories (RLASB) and offers the possibility to work in its Biosafety facility. Coordinators INIA-CISA for RELASB: Dirección ( Maria Luisa Arias Neira arias@inia.es) y Dirección técnica, Lara del Rio delrio.lara@inia.es; INIA-CISA is Reference Centre in Biosafety for FAO (INIA-CISA) Technical Director: Gonzalo Pascual Álvarez gpascual@inia.es;

OIE Reference Laboratory for African swine fever

World Organisation for Animal Health (OIE) Reference Laboratory for African swine fever

OIE Reference Laboratory for African horse sickness

World Organisation for Animal Health (OIE) Reference Laboratory for African horse sickness

European Union Reference Laboratory for Bovine Tuberculosis

The VISAVET Health Surveillance Centre (Universidad Complutense de Madrid, Spain) was appointed as the European Union Reference Laboratory for Bovine Tuberculosis in 2008 (Commission Regulation (EC) No 737/2008)

Facilities

Design, production and characterization of bio- and nanomaterials, body tissues, medical devices and systems, from a physico-chemical, functional, toxicological and biological perspective as part of NANBIOSIS, one of the Spain’s 29 Unique Scientific and Technological Infrastructures (ICTS) recognised by the Consejo de Política Científica, Tecnológica e Innovación (CPCTI of the MINECO) in collaboration with the Centre for Biomedical Research Network in Biomaterials, Bioengineering and Nanomedicine (CIBER-BBN). - U14. Cell Therapy. http://www.nanbiosis.es/portfolio/u14-cell-therapy/ - U19. Clinical Tests Lab. http://www.nanbiosis.es/portfolio/u19-clinical-tests-lab/ - U21. Experimental Operating Rooms. http://www.nanbiosis.es/portfolio/u21-experimental-operating-rooms/ - U22. Animal Housing. http://www.nanbiosis.es/portfolio/u22-animal-housing/ - U23. Assisted Reproduction. https://www.nanbiosis.es/portfolio/u23-assisted-reproduction/ - U24. Medical Imaging. https://www.nanbiosis.es/portfolio/u24-medical-imaging/

Network of High Biosafety Level Laboratories (RLASB) - ICTS (Spanish Scientific and Technical Singular Infraestructures)

The High Biological Safety Laboratories Network (RLASB) is a Unique Scientific and Technical Infrastructure (ICTS) of High Biological Safety laboratories that offers the possibility of using integrated laboratory and animal services, exclusively dedicated to work with infectious agents that demand conditions of high biological security for its manipulation. Due to its size, size and capacity, both High Security Biological Installations are unique at a national and international level, given that there are very few laboratories of these characteristics and this capacity. The RLASB is a distributed ICTS infrastructure formed by two nodes.: (1) BCL-3 of the Animal Health Research Center INIA-CISA, and (2) BCL-3 of the Animal Health Research Center IRTA-CReSA.

Biosafety level 3 Area (BSL3)

Facility that has BSL-3 biosafety laboratories and BSL-3 necropsy room working with biological agents listed in Risk Group 3 (former OIE List A). This area has also a ABSL-3 animal facilities with three individual boxes with air conditioning and independent access to allow the simultaneous performance of different assays and controls.

SEVISEQ Equine Health Surveillance Unit

SEVISEQ (Equine Health Surveillance Unit) is created due to the need of support for the official institutions and is focused on several aspects: the high presence of equine infectious diseases in Spain, the existence of clinical outbreaks, the lack of awareness regarding the importance of equine infectious diseases by horse owners and professionals of the equine industry, and the importance of a correct application of prevention and control measures in every equine premises. The work at SEVISEQ is divided into six lines: - Diagnosis of acute infection. - Analysis of samples prior to exportation and sales. - Analysis of samples for the annual health surveillance in breeding stud farms. - Technical assistance to veterinary surgeons. - Production of health surveillance reports. - Research in equine infectious diseases.

Mycobacteria Unit

Mycobacteria Unit routinely performs bacteriological and molecular diagnose of infections produced mainly by members of the Mycobacterium tuberculosis and avium complexes. Moreover, it realizes studies of molecular and epidemiological characterization. The main lines of research are to set up new technologies for the diagnosis (in vivo e in vitro) of the main principal diseases caused by mycobacteria, as well as the development of new technology for molecular characterization studies. The laboratory also designs field studies of control and eradication programs in problem situations for subsequent implementation at a national level. The laboratory also advises Animal Health Services of the Autonomous Communities, farmers and veterinarians, as well as Ministries. In addition as European Union Reference Laboratory for Bovine Tuberculosis, they provide technical and scientific support to all National Reference Laboratories (NRL) and the official veterinary services of the European Union.

Viral Immunology and Preventive Medicine Unit

Viral Immunology and Preventive Medicine Unit has been developed several lines of research related to the diagnosis of animal viruses (African swine fever, classical swine fever, African horse sickness, bluetongue…) And risk analysis of possible entry and spread of infectious diseases in our country (in addition to those mentioned above, also foot & mouth disease, West Nile, avian flu) The group also develops the tasks of the reference laboratory for the OIE to African swine fever and African horse sickness, and has extensive experience in the management of these and other diseases such as classical swine fever. He also actively collaborates with OIE, FAO, OIRSA, DG SANCO and EFSA. The scientific interest of the service focuses on the study of infectious diseases in animals and in particular the development of new diagnostic techniques, new generation vaccines and new strategies for their control through risk analysis and modeling, as well as establishment of networks for health monitoring.

Foodborne Zoonoses and Antimicrobial Resistance Unit

Foodborne Zoonoses and Antimicrobial Resistance Unit became operational in 1996 based on the Veterinary Antimicrobial Resistance Surveillance Network (VAV). Nowadays, it includes the study of different food-borne zoonoses (Salmonella, Campylobacter, E. coli, Yersinia, Staphylococcus aureus ...). It is also responsible for analyzing antimicrobial resistance in zoonotic organisms, commensal bacteria of the intestinal tract or clinical isolates. The group has several lines of research on the characterization of important foodborne pathogens for Public Health and the mechanisms involved in the emergence and spread of antimicrobial resistance by using molecular tecniques as well as sequencing. It is outstanding the leadership of this group in international research projects and its collaboration with Public Administrations and companies. ZTA gives support to the Ministry of Agriculture, Fisheries, Food and Environment (MAPAMA) and the Community of Madrid developing surveillance programs for zoonotic agents.

Pathology and Forensic Veterinary Medicine Unit

Pathology and forensic veterinary medicine unit currently works on routine diagnosis of infectious and nutritional outbreaks that originate in animal production, mainly pigs, small ruminants and aquaculture. We actively participate in the description of the pathological mechanisms that occur in the development of new vaccines and drug treatments , both experimentally and farms, identifying potential adverse effects. Our group has wide experience in the field of experimental cancer models both the histopathological and immunohistochemical studies, as well as the application of new diagnostic tools such as PROFILING AND IMAGING (MALDI TOF). Actually, our major effort is focused on the development and application of these new technologies to the field of pathology image.

Neglected and Emerging Diseases Unit

Servicio de Zoonosis Emergentes, de Baja Prevalencia y Agresivos Biológicos realiza tareas de vigilancia epidemiológica y monitorización de patógenos emergentes y/o ignorados en distintas especies hospedadores (y en los posibles vectores en su caso). Algunos de estos agentes infecciosos presentan una aparente baja prevalencia, lo que hace que no sean tenidos en cuenta como prioridades en la mayoría de programas de Sanidad Animal a pesar de las graves consecuencias que puede implicar su presencia. La realidad es que la situación real de muchas de estas enfermedades se desconoce, y debido a los cambios en el clima y al incremento en los movimientos migratorios se han creado situaciones favorables para su propagación en entornos inicialmente libres de las mismas. La vigilancia epidemiológica constituye una herramienta útil y eficaz en la prevención y control de posibles brotes. El servicio colabora con administraciones locales y de comunidades autónomas en la monitorización de varias enfermedades.

Microbial Identification and Characterisation Unit

This unit is focused on the study at the phenotypic, genomic and protein leves of pathogenic bacteria of veterinary interest. The main activities of the Unit are divided into three research lines that are closely related: clinical diagnosis (using phenotypic, molecular and chemotaxonomic methods, the molecular characterization of pathogenic bacteria of relevant clinical significance for epidemiological purposes and description of new bacterial species (bacterial taxonomy). The molecular characterization allows tracing epidemiological links between strains associated with outbreaks of disease, global epidemiological studies, monitoring programs, etc. Studies of bacterial taxonomy not only allow the description of new species but also allow, for example, the association of different pathogens with atypical clinical processes.

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