RESEARCH
WHAT ARE WE WORKING ON?
Our multidisciplinary research program combines scientific excellence with a unique market-oriented vision to develop innovative products and technologies for the healthcare industry.
INSTITUTIONAL STATEMENT ON THE USE OF RESEARCH ANIMALS
The Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE) has joined the Agreement on Openness on Animal Research, promoted from the Federation of Scientific Societies in Spain (COSCE), with the collaboration of the European Association of Research Animals (EARA), and launched on 20 September 2016.
OUR LINES OF RESEARCH
The IDiBE research program is organized into two major lines of research that cover all activities carried out by different teams. Each research line is structured in sublines with specific objectives. The aim of this configuration is to make the most of each team’s expertise while favoring the fluent communication and synergies that emerge from multidisciplinarity. We want to promote fruitful internal collaborations, sharing of infrastructures, and productive use of all resources.
PUBLICATION HIGHLIGHTS
At IDiBE we value quality over quantity. We always strive to make significant contributions to society and healthcare and share our results in internationally recognized, peer-reviewed, high impact journals.
1. MOLECULAR DESIGN AND CELL SIGNALING
Studying structure-function relations of molecules and the mechanisms of cell signaling.
The main focus of this line is the structure-function relations of small molecules and macromolecules. With this knowledge, we aim to transform their activity for biotechnological purposes and design better ligands that modulate their function, as well as nanotechnology-based systems that enhance their delivery to the site of action.
An additional objective is to understand the cell signaling mechanisms triggered by environmental signals such as endocrine disruptors and other pollutants that may be the underlying cause of diseases with an increase in prevalence. By identifying the molecular components of these pathways, we seek to validate targets for drug intervention.
This research line involves 8 research groups. The variety of scientific backgrounds of the researchers involved allows for a multidisciplinary approach of these societal and technological challenges.
MOLECULAR INTERACTIONS, PROTEIN BIOPHYSICS AND ENGINEERING
Understanding interactions to rationally design or modify molecules with desirable activities.
DESIGN AND VALIDATION OF NANOSTRUCTURES
Developing nanostructures with healthcare and biotechnological applications.
DESIGN OF ACTIVE MOLECULES
Identifying molecular components with potential applications in healthcare.
MOLECULAR INTERACTIONS, PROTEIN BIOPHYSICS AND ENGINEERING
Understanding interactions to rationally design or modify molecules with desirable activities.
Much of the biological activity of biomolecules is based on their ability to recognize one another and form reversible non-covalent complexes. Molecular interaction processes established in physiological conditions have been evolutionarily optimized in both kinetic and thermodynamic (affinity) aspects, reaching a high level of specificity which confers an exquisite regulation on the existing macromolecular interactions in the cell environment. The main objective of this research sub-line is to understand the principles underlying protein-protein, protein-lipid and protein-ligand interactions, as well as the partitioning of molecules into the cell membranes.
Knowledge about determinants that define the kinetics and energy of macromolecular complexes formation is fundamental for achieving a truly rational design of new biomolecules with the desired activities, or the rational modification biomacromolecules activity such as proteins through the selective modification of their primary sequence (so-called protein engineering). The research projects in this subline are:
Mapping the conformational states of the selectivity filter in ion channels: towards understanding permeation, selectivity and inactivation.
Profs. José M. González Ros
and José A. Poveda
Molecular mechanism of action of direct-acting antivirals against the Zika and Dengue viruses.
Prof. Ana M. Fernández Escamilla
Macromolecular interactions and druggability of intrinsically disordered proteins involved in pancreatic cancer.
Profs. José L. Neira, Javier Gómez and Rocio Esquembre
DESIGN AND VALIDATION OF NANOSTRUCTURES
Developing nanostructures with healthcare and biotechnological applications.
Nanotechnology is currently an essential field in biotechnology, particularly in the design of biosensors for point-of-care usage and the design delivery systems that increase drug targeting and decrease tissue toxicity. This sub-line aims to design nanostructures, including nanoparticles and nanofibers that have biotechnological and healthcare applications. The research projects in this subline are:
Synthesis and design of multifunctional nanostructures for biotechnology and biomedicine applications.
Profs. Ricardo Mallavia, Reyes Mateo and Mª José MartínezTomé
Biosensors based on fluorescent nanosystems for drug screening and health monitoring.
Profs. Reyes Mateo, Ricardo Mallavia and Mª José Martínez Tomé
Design of nanoparticles for drug vehiculization, delivery and controlled release.
Profs. Javier Gómez and Rocio Esquembre
DESIGN OF ACTIVE MOLECULES
Identifying molecular components with potential applications in healthcare.
The identification and design of bioactive molecules for different applications is first based on a computational strategy using molecular modeling, docking and dynamics. In addition, in silico screening is also applied to virtual libraries composed of thousands to millions of molecules from natural and synthetic sources. The research projects in this subline are:
Design of new direct-acting antivirals to Zika and Dengue viruses.
Prof. José Villalaín
Identification of natural and synthetic compounds targeting proteins involved in: energy-sensing; inflammatory/oxidative stress, and aging related cellular pathways.
Prof. José A. Encinar
Design of anti-inflammatory, analgesic and anti-pruritus compounds.
Prof. Gregorio Fernández Ballester
Identification of antimicrobial natural and synthetic compounds by virtual screening on selected protein targets related to antibiotic resistance.
Profs. José A. Encinar, Gregorio Fernández Ballester
ENVIRONMENTAL SIGNALING AND DISEASE
Understanding environmental factors and their role in our health and disease.
ENVIRONMENTAL SIGNALING AND DISEASE
Understanding the impact of environmental factors in our health and developing ways to prevent and treat disease.
It is becoming clear the environment affects human physiology, development, and disease risk. Environmental cues, including radiation, contaminants, and endocrine disruptors, may reach cells and orchestrate changes in signaling pathways that may include alterations in genes and their expression. As these environmental cues are on the rise, their impact in molecular and cellular processes needs to be understood for effective preventive measurements and the design of countermeasures that attenuate or correct their pathophysiological impact. Additionally, generated knowledge may be useful to implement new testing methods and assist national and international agencies to update and/or implement policies that minimize the impact of the environment in health. The research projects in this subline are:
Generation of optimised and integrated approaches for testing metabolic disrupting compounds.
Profs. Angel Nadal, Esther Fuentes, Ivan Quesada
An integrative strategy of testing systems for identification of EDs related to metabolic disorders.
Profs. Paloma Alonso-Magdalena, Cristina Ripoll, Laura Marroquí
Actions of simoultaneous exposure to endocrine disruptors and high fat diet on pancreatic β-cell and risk of type 2 diabetes mellitus.
Profs. Angel Nadal, Esther Fuentes, Ivan Quesada
Effect of sex hormones and endocrine disruptors in nociceptive signaling: implications in chronic migraine.
Profs. Antonio Ferrer and Asia Fernández-Carvajal
2. MOLECULAR DIAGNOSIS, PROGNOSIS AND THERAPY
Identifying molecular pathological markers and developing diagnostic and prognostic methods.
This line pursues the identification and validation of molecular markers in human and animal pathologies of high prevalence. It is also involved in the development of diagnostic and prognostic methods and therapeutic or preventive strategies.
Composed of a multidisciplinary research team, it covers from molecular aspects to semi-industrial biological actives. This multidisciplinarity is sustained by the contribution of 8 consolidated groups, which provide a balanced composition that favors high competitiveness in scientific contributions, raising resources, training research staff and generating exploitable and transferable technologies. A high level of national and international collaborations with public and private research organizations contribute to an increase in the impact of the activities and their internationalization.
The milestones achieved in this line of research have a high scientific impact, as shown by scientific publications in internationally recognized journals, as well as the generation of unique technologies protected by worldwide patents and licensed out to interested companies.
Our high potential for clinical translation has materialized in close collaboration with the University Hospitals of Elche and Alicante. Industrial exploitation of our results has also led to continuous and consolidated collaborations with biotech and pharmaceutical companies.
MOLECULAR ONCOLOGY
Targeting multi-drug resistance to improve treatment and prognosis of cancer patients.
DIABETES AND METABOLIC DISORDERS
Understanding the molecular mechanisms of disease to identify new forms of therapy.
CHRONIC INFLAMMATION AND PAIN
Developing new compounds for the treatment of pain.
MOLECULAR ONCOLOGY
Targeting multi-drug resistance to improve treatment and prognosis of cancer patients.
IDiBE researchers have focused on the appearance of chemoresistance to antineoplastic drugs (also known as multidrug resistance, MDR) and the serious problem that this represents for the treatment of oncological patients.
This has been approached from three experimental and complementary directions. The first looks into the characterization of the molecular alterations associated with the acquisition and development of chemoresistance, by studying the interrelations between MDR, apoptosis, and differentiation in tumor cells, or the mechanisms that regulate the expression of proteins associated to the MDR phenotype at transcriptional and post-transcriptional levels. The final goal of these investigations is to be able to overcome or neutralize the MDR developed by some tumors. The second line of interest is pancreatic cancer, one of the cancers with the worst therapeutic prognostic.
Screening and development of new anticancer compounds targeting energy-sensing metabolism and cell proliferation.
Profs. María Herranz, José A. Encinar, Enrique Barrajón and Vicente Micol
Modulation of multidrug resistance.
Profs. Miguel Saceda and Pilar García
Macromolecular interactions and druggability of intrinsically disordered proteins involved in pancreatic cancer.
Profs. José L. Neira, Javier Gómez and Rocio Esquembre
DIABETES AND METABOLIC DISORDERS
Understanding the molecular mechanisms of disease to identify new forms of therapy.
The main objectives of this subline are to understand the molecular mechanisms underlying diabetes and metabolic disorders and to analyze the effect of fatty acids and aging. It also aims at the identification of new proteins and signaling pathways in pancreatic cells that give protection against stressors of diabetes. These studies aim to identify new therapeutic strategies to combat diabetes, including new selective estrogen receptors.
Complementarily, these studies will focus on:
- A mechanism-of-action profiling-based strategy of pathways related to metabolic stress. This is carried out in cellular models aimed at identifying active compounds and metabolites able to rescue a phenotype consistent in the alleviation of cellular metabolic stress.
- Testing of bioactive molecules designed to alleviate metabolic stress
- Searching for dietary polyphenols able to modulate adipose tissue plasticity from white adipose tissue (WAT) to beige adipose tissue (BAT)
- Assaying the capacity of plant polyphenols to ameliorate metabolic disturbances in hyperlipidemic mice or diet-induced obese mice. Metabolomic analysis to identify changes in metabolites related to energy metabolism.
- Searching for plant polyphenols that modulate satiety-related hormones and peptides in animal models.
- Assaying the effects of plant polyphenols on visceral adipose tissue, cardiac adiposity, regional myocardial function, arterial pressure as well as inflammation and oxidative stress in diet-induced obese mice. Polyphenolic extracts from edible plants for the design of advanced nutraceuticals that modulate energy metabolism: applications in the prevention of obesity.
Actions of simultaneous exposure to endocrine disruptors and high fat diet on pancreatic β-cell and risk of type 2 diabetes mellitus
Profs. Angel Nadal, Esther Fuentes
Study of the mechanisms driving type 2 diabetes mellitus disease.
Profs. Angel Nadal, Paloma Alonso-Magdalena
Function of pancreatic α and β-cell during aging: implications for glucose homeostasis.
Profs. Iván Quesada, Cristina Ripoll
Discovery of new targets for the treatment of type 1 and type 2 diabetes based on pancreatic alpha-cell strategies to survive.
Dr. Laura Marroquí
The role of TGFb signaling in maternal metabolic adaptations during pregnancy: implications for the development of gestational diabetes mellitus.
Prof. Paloma Alonso-Magdalena
Mechanism-of-action profiling pathways related to metabolic stress in cell models aimed to identify active compounds and metabolites able to alleviate cellular metabolic stress.
Profs. Vicente Micol, Enrique Barrajón, and María Herranz
Targeting brown adipose tissue plasticity with dietary plant polyphenols: a new strategy to alleviate metabolic disorders.
Profs. María Herranz, Enrique Barrajón and Vicente Micol
Assaying the capacity of plant polyphenols to ameliorate obesity-related metabolic disturbances and modulate satiety-related hormones and peptides.
Profs. María Herranz, Enrique Barrajón and Vicente Micol
Metabolomic and metabonomic analysis to identify biomarkers and metabolites derived from bioactive molecules and related to energy metabolism.
Profs. María Herranz,
Enrique Barrajón and Vicente Micol
CHRONIC INFLAMMATION AND PAIN
Developing new compounds for the treatment of pain.
This subline is centered in discovering and developing new lead compounds for the treatment of chronic inflammatory pain and chronic pruritus, two nociceptive modalities of the dysfunctional peripheral nervous system. Modulators of the thermoTRP channel TRPV1 have been identified and are currently in clinical development for the treatment of chronic postsurgical pain. This success will be extended to other chronic pain syndromes, as well as to chronic pruritus. The main focus will be towards thermoTRP channels, which are central in the generation of peripheral nociceptive signaling, and pain transduction.
Complementarily, type C phospholipases will be used to develop new analgesic and anti-inflammatory candidates for drug development. These enzymes have been traditionally considered undruggable, but we have developed a strategy that has produced hit compounds with a promising potential for clinical development.
Modulators of chronic migraine and arthritic pain.
Profs. Asia Fernández-Carvajal and Antonio Ferrer
Validations of modulators for undruggable phospholipases as new treatments of chronic pruritus.
Profs. Asia Fernández-Carvajal and Antonio Ferrer
ANTIVIRAL AND ANTIMICROBIAL STRATEGIES
Identification of compounds for the prevention and treatment of microbial and viral diseases.
CLINICAL PHARMACOLOGY
Virtual screening of structural databases for rational molecular design.
ANTIVIRAL AND ANTIMICROBIAL STRATEGIES
Identification of compounds for the prevention and treatment of microbial and viral diseases.
Even though great advances have been made in the field of biomedicine in the past 25 years, infectious diseases of a viral and microbial nature are still a serious problem because of its important health, social and economic impact. For example, the threats from recent viral epidemics, along with the emergence of neglected viral infections are a sufficient illustration of this societal challenge.
Viral pandemics are not only centered on human health but also affect animals. For instance, rhabdovirus infections of salmonids is a notable problem in aquiculture that requires a scientific solution. Similarly, the growing antibiotic resistance represents a noteworthy health problem. In this context, it is evident that the prevention of these diseases is of special relevance in both human and animal health.
Identification of antimicrobial plant extracts and compounds against resistant bacteria. Synergic pharmacological behavior between plant polyphenols and antibiotics.
Profs.José A. Encinar, Enrique Barrajón and Vicente Micol
Detection of resistance determinants and genes associated to antibiotics susceptibility in MRSA treated with antimicrobial plant compounds.
Profs. José A. Encinar, Enrique Barrajón and Vicente Micol
Validation of new direct-acting antivirals to Zika and Dengue viruses.
Profs. Ana María Fernández Escamilla and José Villalaín
Identification of targets in fish nucleated red blood cells to enhance antiviral immunity.
Profs. María del Mar Ortega-Villaizan
Production and evaluation of immune-enhancing and protective effects of antigenic nanostructures against viral diseases of fish.
Profs. María del Mar Ortega-Villaizan and Luís Pérez
Characterization and evaluation of plant extracts with high antiviral and antimicrobial activity against pathogens with significant impact in aquaculture.
Profs. Luis Pérez and María del Mar Ortega-Villaizan
CLINICAL PHARMACOLOGY
Working closely with the healthcare sector to develop compounds for cancer and chronic pain treatment.
The area of clinical pharmacology is focused on two main lines:
- The study of beta blocker drugs in carcinogenesis.
- The pharmacology of chronic pain.
These lines are intimately associated with the University Hospital of Alicante, where part of the research activities is being performed as it involves working with patients.
Design and development of nanostructures for biotechnology and biomedicine applications.
Design and development of nanocarriers as vehicles of biologically active compounds.
Bench-to-factory developments of functional ingredients and nutraceuticals
The design and production of nutraceuticals and functional ingredients requires from preclinical and bench design to semi-industrial scale production, formulation and quality check using high-resolution analytical techniques, as well as validation through human trials.
Various biotechnological processes such as chemical or enzymatic semi-synthesis, fermentation, or biocatalysis may be involved in such developments regardless of their context: human or animal health, nutrition or food purposes. Characterization and safety of these ingredients are crucial requirements to properly commercialize a product in this sector. The main sublines in this area are:
Production of bioactive ingredients and nutraceuticals to be tested in human intervention trials focused on obesity/overweight, diabetes and hypertension.
Profs. María Herranz, Enrique Barrajón and Vicente Micol
Production of polyphenols-based nutraceuticals focused on sports performance, muscular damage prevention and recovery.
Profs. María Herranz, Enrique Barrajón
and Vicente Micol
Bioassay-guided screening of plant extracts and compounds through efficacy cell assays with applications in nutricosmetics, hygiene or medical devices.
Profs. María Herranz, Enrique Barrajón and Vicente Micol
Design, efficacy and safety testing, and formulation of skin health products
Profs. María Herranz, José A. Encinar, Enrique Barrajón and Vicente Micol
Optimization of industrial processes for functional beverage production, and waste management for nutraceutical ingredients, all with a bio-economy perspective.
Profs. Domingo Saura López and Nuria Martí Bruñá
Semi-industrial scale production of nutraceuticals from plants, herbs or by-products.
Prof. Domingo Saura López and Nuria Martí Bruñá
Identification & Purification of bioactive molecules from waste management, and small-scale production herein for biological pest control.
Profs. Domingo Saura López & Manuel Valero Roche
Identification, isolation, culture development and pilot plant scale production of microorganism for feedstock.
Prof. Manuel Valero Roche
Development of new nutritional products from fermentation processes.
Profs. Manuel Valero Roche and Nuria Martí Bruñá
Identification, purification and production of bioactive molecules in functional drinks, fermented drinks, beer and wine.
Prof. Nuria Martí Bruñá
Formulation, development and pilot plant scale production of cosmetic and food functional products.
Profs. Domingo Saura López, Manuel Valero Roche and Nuria Martí Bruñá
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