The research group has an extensive experience in the study of molecular mechanisms that regulate the adaptation to changing environmental conditions of lichenic microalgae and vascular plants and their biotechnological application. This type of studies has been developed in different research lines:
a) Transcriptomic and metabolomic analysis of the response of lichenic microalgae to extreme conditions such as salinity, drainage and radiation.
b) Biotechnology of lichenic microalgae: transformation and obtaining natural products.
c) Characterisation of polyamine metabolism in the stress response of Arabidopsis thaliana. By means of transgenic manipulation, the polyamines (PAs) biosynthesis process has been manipulated, resulting in the obtaining of different plant lines with altered levels of putrescine, spermidine and/or spermine, which have been characterised at different levels, including metabolomic and transcriptomic studies. Most of the lines generated, plants with high levels of one or more PAs, show resistance to different environmental and biotic stresses.
d) Regulation of transcriptional programmes by DELLA and prefoldin proteins. These proteins act as transcriptional regulators whose accumulation depends on environmental conditions and which modulate the execution of multiple developmental programmes and stress responses by modifying the activity of transcription factors with which they physically interact.
Women present a specific profile in many areas of ageing, including frailty, chronic diseases (examples are clearly musculoskeletal diseases, cardiovascular diseases, certain forms of cancer, cognitive impairment or depression), social interaction, and quality of life.
Our activity has focused on the female determinants of osteoporosis and cardiovascular diseases, quality of life after menopause, cognitive impairment and, more recently, frailty. More recently, we have also been doing research on endometriosis, a disease that causes morbidity and affects quality of life, and whose impact on healthy ageing is just beginning to be understood.
We have carried out basic and applied research work, and are therefore an example of a multidisciplinary group with interaction between basic and clinical researchers and with a profile of publications and funded projects that meet this criterion.
- Genetic analysis in solid tumours in children. At European level, we participate in the establishment of a uniform nomenclature, a standard operating procedure and quality validation studies, essential to obtain and maintain a high quality of the results of fluorescent in situ hybridisation, single nucleotide polymorphism and sequencing (FISH, SNPs and NGS) used for therapeutic stratification in neuroblastoma.
- Identification of new genetic factors and digital microscopic analysis with prognostic value in low prevalence tumours (rare tumours).
- Obtaining and characterising cell lines derived from fresh tumours of neuroblastic and skeletogenic tumours in children.
- Establishment and characterisation of in vivo models (2D and 3D) of neuroblastic tumours.
- Marker expression studies in paediatric solid tumours and colorectal carcinoma.
- Digital pathology studies of the tumour microenvironment.
Studies of prokaryotic diversity in aquatic environments (especially marine) and bacterial taxonomy.
- Polyphasic characterisation of bacteria and archaea, especially marine, for taxonomic purposes, formal description and conservation of new bacterial taxa and generation of databases useful for their identification.
- Phenotypic and functional characterisation: cultural, structural, physiological, biochemical and nutritional characters, determination of chemotaxonomic characters (fatty acids, polar lipids, quinones, majority proteins by MALDI-TOF, G+C).
- Comparative genomics applied to prokaryotic taxonomy: obtaining data (new sequences, extension and/or closed) of type strains and new isolates, comparative analysis and phylogenetic studies based on conserved genes (16S rRNA gene, various essential genes), phylogenomics based on complete genomes. Determination of in silico DNA-DNA hybridisation values and ANI (Average Nucleotide Identity) and AAI (Average Aminoacid Identity) indices from genomic sequences.
- Formal aspects: Nomenclature in prokaryote taxonomy.
Taxonomic groups: preferably families, genera and species of the phyla Pseudomonadota (especially families Vibrionaceae, Halomonadaceae and Rhodobacteraceae) and Bacteroidota (order Flavobacteriales), among other taxa.
Our group started originally over forty years ago. A major founding milestone was the postgraduate study of Dr Jose Viña with the late Sir Hans Krebs at the University of Oxford. This has led the whole Group to a "metabolic-oriented approach to problems" as it could not be otherwise stemming from Sir Hans Krebs. Upon his return to Spain, Dr Viña started a small group in the University of Valencia that has been working, on and off, for the last thirty-five years. Sometimes Dr Viña was away from the University of Valencia, but the seed of the Group had been sown. Very seriously established scientists like Dr Federico Pallardo, Dean of the Faculty of Medicine - University of Valencia, Dr Juan Sastre, Dr Jose Estrella, Dr Guillermo Saez, all of them professors of biochemistry or physiology at the University of Valencia, the late Dr Navarro, University of Cadiz and Dr Juan Llopis, University of Albacete started their scientific work in this group and latar established their own successful independent groups.Some twenty years ago the major hard-core members of the Group in its present form came to the laboratory and these include Dr Ana Lloret, Dr Carmen Gomez-Cabrera and Dr Consuelo Borras. All the three are now very well established scientists and form the backbone of the Group. Other permanent members include Dr Juan Gambini, Dr Marta Ingles, and Dr Gloria Olaso. For over twenty years we have been blessed by the help of Marilyn Noyes; she has been integrated in the Group for all these years and we hope for many more to come.
Our collaborations with many colleagues, indeed friends, in Spain are so frequent that we would not like to highlight any of them. We are delighted to have all these friends around the country.
We have established close connections with other labs around the world. Some examples include the labs of Dr Giovanni E Mann and of Dr Malcolm Jackson in the UK, Dr Giuseppe Poli in Italy, Dr Helmut Sies and Dr Tilman Grune in Germany, Drs Delamarche in France, Drs Boveris and Dr Fraga in Argentina and Dr Bruce Ames, Dr Packer, Dr Orr and Dr Li Li Ji in the US.
There is a continuous renewal of our Group and we are happy to have had temporary members in the team from Spain, not only from Valencia, but also from France, Italy, Portugal, Morocco, Argentina, Sahara, or Japan. The names of Dr Frédéric Derbré, Dr Gaetano Serviddio, Dr Diana Rus, Dr Jelena Marcovic, Dr Nancy Mora and Dr Mika Jikamaru are just a few examples of this international collaboration. These have been indeed very interesting people who have come to us and have contributed to the pleasant spirit of this team. We consider ourselves as a "scientific family" and hope we will continue contributing to biomedical research and enjoying life at our laboratory.
Laboratory authorised to work with quarantine plant pathogenic bacteria (biosafety level 2 conditions).
Lines of research:
- Characterisation and diagnosis of plant pathogenic bacteria.
- Description: Conventional and molecular diagnosis, characterisation and identification of plant pathogenic bacteria (phytopathogens). Molecular typing and epidemiology.
- Activities: Use of rapid and specific molecular methods for the detection and diagnosis of plant pathogenic bacteria (quarantine bacteria such as Erwinia amylovora and Ralstonia solanacearum and other plant pathogens in general such as Lonsdalea quercina, Brenneria spp. etc.).Molecular epidemiology studies to determine intraspecific variability and pathways of introduction/dissemination of bacterial pathogens. Virulence and/or pathogenicity tests with different phytopathogenic bacteria.
- Survival strategies of plant pathogenic bacteria.
- Description: Bacterial survival strategies in different environments [survival in oligotrophic conditions, viable non-culturable state (VNC) and inducing factors], reservoirs and transmission pathways. Recovery of bacteria in VNC state. Gene expression and obtaining mutants in bacterial genes of interest.
Activities: Studies of survival of phytopathogenic bacteria in natural water microcosms and/or other environmental reservoirs.Studies of reservoirs of phytopathogenic bacteria and transmission pathways. Studies of factors inducing entry into the VNC state. Studies of recovery and/or resuscitation of VNC cells. Studies on the effect of biotic and abiotic factors on the survival and pathogenicity of phytopathogenic bacteria. Studies of the effect of different stress factors on the expression of genes related to the survival and/or virulence of phytopathogenic bacteria. Obtaining mutants in genes related to the survival and/or virulence of phytopathogenic bacteria. Studies of the survival and virulence of bacterial mutants of plant pathogens Characterisation of bacterial mutants of plant pathogens by microbiological, microscopic, molecular and/or omic techniques.
- Biotechnological applications of environmental micro-organisms.
- Description: Isolation and characterisation of environmental micro-organisms of biotechnological interest: bacteriophages, micro-organisms producing antimicrobial compounds, siderophores, degrading micro-organisms. Biological control of bacteriosis in plants.
- Activities: Isolation and characterisation of specific bacteriophages of phytopathogenic bacteria. Survival studies of specific bacteriophages of phytopathogenic bacteria. Isolation and characterisation of microorganisms producing antimicrobials and other metabolites of interest. Biological control of bacterial plant diseases. Isolation and characterisation of hydrocarbon-degrading environmental microorganisms. Study of possible applications in bioremediation.
- Bacteriology of lichens. Biotechnological applications.
- Description: Isolation and characterisation of lichen-associated bacteria: diversity, contribution to lichen symbiosis, and biotechnological applications.
- Activities: Isolation of bacteria associated with lichens. Obtaining lichen extracts. Optimisation of the recovery of lichen bacteria. Diversity of lichen bacteria. Role of lichen-associated bacteria in lichen symbiosis. Biotechnological characterisation of lichen bacteria and their applications: plant growth promoting microorganisms, waste degraders, producers of new polymers, pigments, etc.
The researcher is focused on studies of biodiversity, ecology and evolution of hidroids (Hydrozoa Class, Phylum Cnidaria). The main focus is on Antarctic benthic hydroids fauna. It is one of the most diversified and characteristic zoological groups of the Antarctic ecosystem and has a number of important peculiarities crucial to understanding its origin and evolution, such as relatively low diversity at the generic level, a high degree of endemism at the specific level (almost 80%), centred on a few genera, and a specific diversity also concentrated in a few groups.
The work carried out so far has significantly increased the knowledge about the biodiversity of the Antarctic group, also providing important information on the biology, ecology and biogeography of the discovered species species. As a result of these studies, and only considering the biodiversity of the group, the description of more than 50 species new to science has contributed to increase the inventory of known species by almost 37%. The results obtained are used in phylogenetic studies to increase knowledge about the origin and evolution of this interesting zoological group.
Besides research on Antarctic hydroids, studies on this group are also carried out in other geographical areas, such as the Mediterranean or the Pacific. In addition, species revisions of several genera are carried out with the aim of increasing scientific knowledge of this class of cnidarians.
The research of the Biotechnological Pest Control group of the Universitat of València aims to optimise Integrated Management strategies designed for the control of pests of agronomic interest. The group's funding is supported by research projects and contracts financed by public and private entities. We are working specifically on three research lines, the objectives of which are summarised below:
- Study of the genetic and biochemical bases of pesticide resistance in order to delay pest emergence and avoid the phenomenon of cross-resistance.
- Development of new bioinsecticides: Extending the known spectrum of action of B. thuringiensis and the search for new entomopathogenic viruses.
- Insect-pathogen interaction: Identifying the mechanisms involved in the response to pathogens.
Research activity focused on the conservation and improvement of forest and aromatic species. It comprises two lines subsidised by MINECO, EU and Valencian Government (PrometeoII):
- Biotechnology of forest species. Apply somatic embryogenesis (SE) as a tool to increase the resilience of forest species for sustainable forestry. In recent years, we have optimised HE protocols in Pinus pinaster (maritime pine) and Quercus ilex (holm oak), highlighting the selection of Pinus pinaster families with high embryogenic capacity; the creation of a germplasm bank with these lines; the development of genetic transformation protocols in maritime pine and stone pine; and the development, for the first time, of a protocol to establish embryogenic lines of adult holm oak genotypes. The current project (AGL2013-47400-C4-4-R) addresses two strategies for breeding stress-tolerant genotypes. One takes advantage of natural variability and uses the protocols developed to clone and test holm oak genotypes with and without "la seca" symptoms; the second aims to induce epigenetic memory "priming" by applying biotic and abiotic stress treatments during the proliferation-maturation phase. The project also addresses various physiological and molecular aspects of the embryogenic process as a strategy to improve the induction and maturation phases. We collaborate with national forestry HE expert groups from IMIDRA, CSIC and Neiker. The group participates in national and European initiatives using maritime pine as a conifer model for functional genomics studies. In the SustainPine project (Plant-KBBE, PLE2009-0016) we generated transgenic plants with variable levels of expression (overexpression, or silencing with RNAi) of genes involved in growth associated with nitrogen metabolism and which are in the process of evaluation. We also participate in the European project ProCoGen (FP7-KBBE-2011-15) generating a haploid maritime pine cell line that is being used as a source of DNA for the sequencing of its genome.
- Metabolic engineering of terpenes. It studies the mechanisms that regulate the synthesis and accumulation of terpenes in glandular trichomes of lavender (Lavandula latifolia). All terpenes are derived from the C5 precursor IPP (isopentenyl bisphosphate) and its isomer DMAPP (dimethyl allyl bisphosphate), which in plants can be synthesised via two routes, the cytoplasmic (MVA route) and the chloroplastic (MEP route). To study the contribution of both pathways to final essential oil production, we overexpressed in lavender Arabidopsis genes involved in the first steps of both pathways. We show that the enzyme 1-Deoxy-d-xylulose-5-phosphate (DXP) synthase (DXS), which catalyses the first step of the MEP pathway, plays a crucial role in IPP biosynthesis as its overexpression increases essential oil production in leaves. In contrast, overexpression of the enzyme DXP reductoisomerase (DXR), which catalyses the conversion of DXP to MEP, is not a limiting enzyme in the process. Overexpression of HMG1 (cytoplasmic) also significantly increased essential oil production suggesting an interconnection between the two pathways. To study the contribution of the MVA route to the biosynthesis of lavender oil, studies have been carried out with labelled precursors showing that although the chloroplastic route is the most important, under certain conditions there may be a flow of cytoplasmic IPP into the chloroplast. The essential oil profile has also been modified by overexpressing the linalool and limonene synthase genes without altering the total oil content. The glandular trichome isolation technique is being optimised to complete metabolic studies.
Since 2009 we have been working with the company SAT Even 46 CV to produce healthy mother plants of oleander varieties.
Our group develops its research activity in the following areas:
- Dental pathology: epidemiological and clinical studies.
- Public health and primary care dentistry.
- Tooth whitening.
- Endodontics: biomaterials and techniques.
- Restorative dentistry: materials and techniques.
The Environmental and Biomedical Viruses Lab is located at the Insitute for Integrative Systems Biology (I2SysBio, UV-CSIC). Research at the EnBiVir lab is focused in the isolation and detection of viruses in nature with biomedical applications. Environmental virology, viral emergence, virus evolution, and phage discovery in the biomedical context, are the main research lines. Phages are ubiquitous in the environment and immensely diverse, making phage discovery a powerful source of new therapies against pathogenic bacteria, due to the emergence of multidrug-resistant strains. In addition, the lab is interested in environmental epidemiology, mainly in SARS-CoV-2 detection in wastewater and other natural environments, as a tool for monitoring populations and as early detection tool in surveillance. In addition, the group is interested in translational research, and has transfer contracts with national companies with biomedical and biotech purposes.
Our group studies how cells attach to the extracellular matrix (ECM) and its implications. Cell-ECM adhesions modulate mechanical signals and control growth factor signalling, determining cell survival, differentiation, migration and extravasation. ECMs are organised into fibrillar lattices of varying complexity to which cells attach via specialised membrane receptors, such as integrins, that act as a link to the cytoskeleton. Among the proteins and proteoglycans that make up ECMs, the fibronectin (FN) protein is particularly interesting as it offers multiple cell adhesion motifs and its polymerisation is the initial step for the organisation of the rest of the components of many ECMs, mainly those that promote embryonic development and those transient matrices that allow tissue regeneration and tumour development.
FN is secreted as a soluble dimer and its polymerisation depends on the cell, as only if it binds to integrins and these are activated and stimulate the contractility of the cytoskeleton does it exert traction on the FN allowing it to unfold and self-polymerise. Fibronectin fibres are undergoing continuous remodelling and disruption of this process can lead to fibrosis, arthritis and defects in development and angiogenesis.
In our group, we have generated and analysed different strains of fibronectin-expressing knock-in and conditional knock-in mice with mutations in residues potentially critical for cell adhesion. We are interested in which adhesions are really limiting and how each adhesion influences cell behaviour and ECM secretion, structure, maintenance or stiffness; factors that ultimately determine tissue formation and regeneration. We are using these mice to find out how essential proteins or sequences involved in adhesion are in vivo and to define pathologies caused by their deficiency. Regions of the FN that we consider crucial to its function:
- the RGD motif of the FNIII10 module is the main integrin-binding sequence. FN-RGD adhesion is very complex: it has been said to be the only one that allows the formation of FN polymers; it links two distinct families of integrins:
- the first consisting of Alpha5Beta1 and AlphaIIbBeta3 (exclusive to platelets);
- Alphav-containing dimers, with different, but in many tissues complementary, functions. It has been described that in the first group, adhesion is enhanced, under conditions of increased stress, by the binding of an amino acid sequence, called the synergistic site, which is located in the FNIII9 module.
- the heparin II region (modules FNIII12-14) which on the one hand binds Syndecan-4, another cellular receptor, and on the other hand binds numerous growth factors involved in angiogenesis and cell proliferation, such as the FGF family, the TGFBeta family and the PDGF family. This region has been hypothesised to allow signalling by growth factors in a cooperative manner with RGD adhesion. This region is of particular interest in the area of tissue regeneration.
Our fundamental interest is to understand how cells respond to the signals they receive by modifying their gene expression. Our aim is to address changes in gene expression by studying its different stages, from the transcriptional activation of genes to the formation of messenger RNA molecules and their translation, paying attention not only to the factors involved and the mechanisms, but also to the connection or crosstalk that is established between them and makes gene expression not a linear process but one that is interconnected forwards and backwards, in time and space.
In addition, we pay special attention to some factors that appear to be key in the control of gene expression and that often act in a multidisciplinary way in several biological processes and different cellular compartments. One such factor is the eIF5A protein, highly conserved from yeast to humans and essential in eukaryotic cells. eIF5A is a translation elongation factor required in the synthesis of proteins containing amino acid motifs with consecutive proline or combinations of proline, glycine and charged amino acids.
Our interest is to understand the mechanism of translation regulation by eIF5A, determining which are the proteins whose synthesis requires this factor and how, directly or through its targets, eIF5A acts in pathological processes such as fibrosis, cancer or during ageing. In our group, we mainly use the yeast Saccharomyces cerevisiae as a model organism, since it is the best known eukaryote and a model for understanding evolutionarily conserved molecular processes at the cellular level. Furthermore, we have found that the conclusions of our research can be generalised to mammalian cells using mouse or human cell cultures.
Multidisciplinary biomedical research group established in 1998 within the EPIGEM (Genetic and Molecular Epidemiology) Research Unit, recognised at the Universitat de València. This group was recognised by the Valencian Government in 2000 and again by the Valencian Government as a group of excellence in 2004. Since then, it has participated in research on genetic and environmental risk factors in the aetiology of complex diseases, mainly cardiovascular diseases and their risk factors including obesity, diabetes, dyslipidaemia, etc. Since 2003 it has been part of the PREDIMED study and is currently part of the PREDIMED PLUS study. Since 2006 it has been part of the CIBER Physiopathology of Obesity and Nutrition. The group has more than 350 publications in scientific journals. It has participated in more than 30 public and private research projects and is a pioneering group in Nutritional Genomics.
This Research Group focuses on the analysis of the strategic decision-making process and human resources strategy, relating it to organisational knowledge management, innovative employee behaviour, entrepreneurial behaviour and corporate sustainability. In particular, it studies how HR policies serve as key factors in facilitating the implementation of knowledge management processes (acquisition, creation, storage, sharing, application and distribution) in organisations, generating innovation and entrepreneurship-oriented behaviours of individuals.
The analysis of how HR policies and their joint or systemic consideration become a catalyst for the individual's creativity and interest in developing innovations (new products, new processes or even new business projects) at the organisational level, which can contribute to the achievement of sustainable competitive advantages. In addition, the implementation of sustainability-oriented HR practices will, at the same time, enable the development of individual and collective behaviours that meet the current challenges that organisations face in terms of social responsibility and business sustainability. Likewise, the fact that knowledge has recently become a strategic resource for organisations has highlighted the need to manage it actively and with a clear strategic orientation. Therefore, the study of all knowledge management processes and how they are affected by the organisation's HR strategy is a subject of study for this Research Group. In turn, these knowledge management processes are essential to create the necessary climate for employees and groups within organisations to develop innovative and entrepreneurial behaviours.
The research projects developed within the framework of the team have an academic and applied orientation, and focus on collaboration with companies and managers to improve their management, with special emphasis on the problems of SMEs.
Our research activity focuses on studying mechanisms of pathogenesis and discovering potential drug therapies for rare diseases of genetic origin, in particular Myotonic Dystrophy (DM1 and DM2), Spinal Muscular Atrophy (SMA) and Limb-Girdle Muscular Dystrophy (LGMDD2). To this end, we used Drosophila as an initial experimental model, whose genome we manipulated to create suitable models for our studies. We apply the results obtained in cell cultures, murine models or human samples. One of our main objectives is to identify and develop drugs from both repositioning strategies and RNA oligonucleotide-based drugs.
The group is composed of several researchers from the departments of Computer Science and Statistics and Research. Operational with a long history of working together, along with the incorporation of other people who arrived later to the Computer Science department and several collaborators, also linked by previous joint research, from the Universitat Jaume I of Castellón. The most general common nexus is computer vision and image analysis, both 2D and recently 3D, with a special focus on medical imaging and the one generated by biological processes. The common goal is to provide experience, curriculum and applicable solutions to medical or industrial problems related to image analysis, shape analysis, reconstruction and modelling of anatomical structures and retrieval of information from image databases. Due to the complexity of the software that must be developed, a formal vision which deals with the modelling of the software and its interaction with the user is necessary. In particular, the research activity carried out to date, and which is intended to be given even greater cohesion, is organised along the following lines:
- Segmentation and co-registration of anatomical structures, in particular from radiology images, magnetic resonance images, positron emission tomography (PET) images or other modalities, if required. The statistical analysis of the shapes obtained for their comparison, indexing or modelling requires the use of morphometric techniques that connect this line to the next.
- Morphometry, understood as the statistical analysis of shapes, both 2D and 3D, to determine their temporal variations or between groups of cases and to obtain representative prototypes of shape classes.
- Computational Physiology, understood as the multi-scale modelling of biological and medical processes by means of ICT tools to better understand pathophysiology and improve the diagnosis and treatment of diseases. Larger scale modelling (organs) connects this line to the previous one, as long as shape analysis is applied to organs such as the liver or the heart; smaller scale modelling connects it to the next line,
- Stochastic spatio-temporal models for the analysis of dynamic processes from image sequences. In particular, statistical methodologies based on univariate and bivariate germ-grain processes that have been used so far to model processes in cell biology is applied by analysing images generated by confocal microscopy.
- Image and shape retrieval based on the visual content of large image or shape databases, in general, not manually labelled with a descriptive text, with special focus on human morphometry and medical image databases. This supports the organisation and semantic description of the case studies used in previous lines.
- Software production methods and modelling of software interaction with the user. This transversal line analyses and arranges the software produced (in fact, the main applicable outcome of our research) so that it is correct, reusable, extensible and easily manageable (in the case of final products) by content-competent but non-computer-specialised users, in particular doctors or health personnel. The applicability of this research is ocused on the biomedical area, and has its ultimate goal in clinical application. However, there are interesting derivations in fields such as basic research in areas like cell biology, or material science and other more direct practical utilities (design of communication and sensor networks, clothing design, shopping recommendation systems that use the visual aspect of objects, etc.).
Since 1986 we have been studying the brain of reptiles, birds and mammals. Our aim has been to understand the common traits of organisation of the vertebrate brain. In this never-ending task we have focused our attention mainly in the amygdala, but also in other structures of the 'limbic' forebrain such as the septum and hippocampus, as well as in the visual systems at all levels (from the retina to the visual cortex). We have collaborated with several grups from Europe and the USA, such as those of Luis Martínez-Millan (Euskal Herriko Unibersitatea, Leioa, Spain), Tomás González-Hernández (Universidad de La Laguna, Tenerife, Spain), Salvador Guirado (Univ. Málaga, Spain), Piet Hoolgand (Vrije Universiteit, Amsterdam, The Netherlands), Jeús Perez-Clausell (Universitat de Barcelona, Barcelona, Spain), Margarita Belekhova (Russian Academy of Sciences, Saint Petersburgh, Russia), Ceri D Davies (Imperial College, London, UK) and Mimi Halpern (State Universty of New York, Health Science Center at Brooklyn, USA). We are currently collaborating with Joseph LeDoux, (New York University, USA), Alino Martinez-Marcos, (Univ. Castilla La Mancha), Jane Hurst (Univ. of Liverpool, UK), Karim Nader (McGuill Univ, Canada), Mike Ludwig (Univ. Edimburgh) and Trése Leinders-Zufalla and Pablo Chamero (Saarland Univ., Germany).
Our main lines of research are:
- Anatomy of the amygdala. Our main goal is to try to characterise the organisation of the amygdala, a portion of the brain involved in both chemoreception and emotions. This functional heterogeneity parallels the anatomical complexity ofthe amygdala which includes derivatives of the embryonic pallium (thus, portions of the cerebral cortex), of the subpallium (striatum and pallidum) and even of portions of the hypothalamic neuroepithelium. We are using tract-tracing techniques and the presence and distributoin of many neurochemical markers.
- Neurobiology of the reinforcing properties of sexual pheromones in mice. In fact, the cortico-medial and basolateral-central divisions area apparently involved in independent functions, related to chemosensibility (cortico-medial) and to eliciting innate and learned emotional responses (basolateral-central). The results of our research on the reinforcing properties of a vomeronasal stimulus, sexual pheromones in mice, suggest that both functions of the amygdala are interrelated, thus giving a functional explanation for the profuse interconnections found between the different divisions of the amygdala in different vertebrates.
- The neural basis of maternal aggression. In the last years we have moved to further understand the role that the amygdala and its connections with the rest of the brain are playing in the control of soxio-sexual behaviour in response to conspecific chemosignals, e.g. pheromones. We are currently analysing how the brain of female mice changes from a regular status in which the animal likes male pheromones, to a maternal status in which the female fiercely attacks male intruders. This will allow better understanding the neural basis of aggressive behaviour. In this respect we are developing two lines of research:
- Neuropeptides and sociosexual behaviour. In the change from attraction to aggression ocurring in the brain of lactating females, the circuits using neuropeptides (especially vasopressin and oxytocin) are likely fundamental. Therefore we are currently analysing these nonpeptide-containing circuits in the brain of males and of females in different physiological situation.
- Neuroendocrinology of maternal aggression. In addition, we are trying to understand the endocrine agents acting during pregnancy, delivery and lactation, that may explain this behavioural changes in females. We are currently exploring how sexual steroids and prolacting combine their actions to promote maternal behaviours including aggression.
Lines of work:
- Ecology and diversity. Taxonomy. Molecular methods of detection and identification. Studies on the ecology of yeast and bacteria species in wine. Taxonomic analysis and description of new species. Development of different methodologies for the detection, identification and quantification of organisms present in wine. Quality control. Control of the implementation of starter cultures.
- Metabolisms of sugars, acids and aminoacids in lactic acid bacteria. This line of work is aimed at understanding the ability of microorganisms to use substrates present in must or wine, to determine how these substrates affect bacterial growth, and to determine the effect of their use on wine characteristics.
- Genetics, genomics and proteomics of Oenococcus oeni. O. oeni is the species responsible for malolactic fermentation in wines, a process that enhances the qualities of aged red wines. Most malolactic starter cultures are strains of this species. The aim of this line of work is to develop tools for the genetic manipulation of this species: plasmids for cloning, malolactic mutants and DNA introduction systems, etc. Comparative genomics studies to establish relationships between genome and resistance to wine stress factors.
- Malolactic fermentation. Selection of O. oeni and Lactobacillus plantarum strains as malolactic cultures. Development of advanced strategies to carry out malolactic fermentation: immobilised cells, continuous deacidification, non-proliferating cells. Adaptation of strains to SO2 and pH.
- Selection and adaptation of bacteria and yeasts to mitigate the effects of climate change. Correction of imbalances in the composition of musts and wines. Biological acidification of wines. Biological reduction of alcohol content.
- Microbial or enzymatic systems to remove toxic biogenic amines in food. Search for strains of lactic acid bacteria capable of degrading biogenic amines in wines. Search for enzymes responsible for the degradation of biogenic amines. Development of cellular and enzymatic systems that allow their use in wines and other food.
The Biochemical and Molecular Genetics group of the Genetics Departmentof the Universitat de València has focused our research activity in the field of plant protection. Sustainable development, particularly in agriculture, is nowadays recognised as a common priority objective for humanity. The use of agrochemicals, specifically pesticides, is being limited and great efforts are being made in R&D&I to find and select new biological insecticide products that cause less damage to the ecosystem than chemical insecticides, and also the development of plant defence inducing treatments based on natural compounds, as an alternative to the massive use of synthetic products. In addition, the possibility of early detection of biotic and abiotic stress conditions in plants could prevent important losses of crops of interest and reduce dependence on pesticides.
Our research is focused on three basic lines:
1. Mode of action of Bacillus thuringiensis (Bt) toxins on different insect pests.
Bioinsecticides and transgenic crops based on Bt, which are environmentally and health friendly, constitute a viable alternative for biological control.
The pathogenesis of Bt lies mainly in the insecticidal proteins produced during sporulation of the bacterium, which have been described to exert their insecticidal action through a mechanism comprising different steps. Our research is focused on understanding the molecular basis of the Bt toxins mode of action and their specificity in different insect orders in order to use the knowledge gained in the rational design of improved toxins to generate safer and more potent insecticides and to address problems that may compromise the use and efficacy of Bt in the field, such as the insecticidal spectrum or the emergence of resistance.
2. Natural plant defence mechanisms against pathogen attack.
Hexanoic acid (Hx) is a natural compound that acts as an inducer of plant defences through a priming mechanism, with a possible broad spectrum of action. The initial finding that Hx protects tomato plants against the fungus Botrytis cinerea led to the extension of its use to other pathosystems and to a patent for the use of short-chain monocarboxylic acids to protect plants against various stresses. This invention is currently marketed under the name Induct.
Our research is focused on studying the molecular mechanism underlying the Hx priming process by identifying new proteins through massive and targeted proteomic analysis. In addition, we are interested in analysing the effect of Hx treatment as an enhancer of Bt toxin action and the incorporation of this plant defence inducer in integrated pest management strategies.
3. Early detection of stress in plants.
Early detection of stress in crops of agronomic interest is critical for efficient plant protection to minimise losses and optimise treatments.
Our research in this area focuses on the characterisation of general stress biomarker profiles or specific stress biomarkers in tomato plants in response to biotic or abiotic stresses using two approaches: i) expression analysis of genes involved in defence mechanisms against biotic stress identified in previous transcriptomic analyses; ii) identification at genomic level of miRNAs by massive sequencing, which on the one hand can serve as biomarkers themselves, and on the other, will allow the discovery of new target genes involved in stress response and provide information on their gene regulation processes.
Copper and iron are essential micronutrients for all eukaryotic organisms because they are involved as redox cofactors in a wide range of metabolic processes, such as energy generation in organelles and lipid biosynthesis. Physiological, biochemical and genetic studies have revealed the large number of connections between copper and iron homeostasis, which must necessarily be studied simultaneously. In our group, we use the yeast Saccharomyces cerevisiae and the model plant Arabidopsis thaliana in combination to explore conserved mechanisms of response to sub-optimal levels of copper and iron, with the aim of developing biotechnological applications in agriculture and human health.
An important part of the control of the response to metal deficiency occurs at the post-transcriptional level, as corroborated by studies with mammalian iron regulatory proteins. In this regard, we study the involvement of mRNA degradation and translation machineries in the response of yeast cells to alterations in iron and copper levels, with special interest in the conserved RNA-binding protein Cth2, which controls cellular iron metabolism. In addition, we studied the role of Cth2 homologues in Arabidopsis in the response to metal deficiencies such as copper, iron and zinc, as well as the contribution of metal-regulated microRNAs to copper and iron homeostasis. Rising temperatures caused by climate change and the rise of organic farming are contributing to an increase in fungal pathogens in plants, which challenge food safety and quality. We explore the role of iron and copper in two important pest control strategies. First, iron is essential for the biosynthesis of unsaturated fatty acids and ergosterol, which determine the fluidity of cell membranes. The ergosterol biosynthesis pathway is used as a target for treatments with antifungal compounds. We use S. cerevisiae to study the connections between iron and lipid metabolisms, with the aim of finding out how iron modulates fungal resistance to antifungal compounds. Secondly, the excessive and toxic accumulation of copper in soils and in the edible part of plants is affecting agriculture in general and oenology in particular. Grape musts have high levels of copper that alter the quality and safety of wines. We will determine the tolerance and copper extraction capacity of a large number of Saccharomyces species and strains of oenological interest, which can contribute to reducing the detrimental effect of copper on wines. Finally, iron deficiency anaemia is the most widespread nutritional disorder in the world, with a greater impact on women and children. Food fortification and iron supplementation are strategies used to prevent and treat iron deficiency in humans and animals. We will exploit the recently characterised genomic sequence diversity in Saccharomyces species to obtain iron-enriched yeasts that can be used as iron supplements or for fortified bakery products.
The Molecular Oncology group is strongly involved in translational research in cancer with special interest in the search for biomarkers related to angiogenesis, immunoregulation and tumour stem cells in cancer, characterised by its multidisciplinary nature. The team includes researchers with expertise in different areas such as: molecular and cell biologists, clinical oncologists, thoracic surgeons, pulmonologists, pathologists and immunologists.
The group's research activity is linked to the General University Hospital of Valencia, a tertiary reference hospital in Valencia, and is closely associated with the activity of three important specialised departments: Medical Oncology (about 648,000 inhabitants), Thoracic Surgery (760,000 inhabitants) and Functional Breast Unit (648,000 inhabitants). They are also very active in recruiting patients for clinical trials.
The main lines of translational research of the group are:
1) Molecular markers in lung, colorectal, melanoma and breast cancer, mainly focused on early diagnosis and the search for prognostic and predictive factors of response to treatment through different omics approaches (genomics, transcriptomics, metabolomics).
2) Liquid biopsy: for the analysis of markers in minimally invasive samples.
3) Angiogenesis and immunoregulation. Study possible interrelationships between tumour neovascularisation, the presence of immunoregulatory cell populations (Tregs cells, myelosuppressive cells, dendritic cells) and tumour recurrence or progression.
4) Tumour stem cells (CSC): characterisation and isolation of CSCs from lung cancer patient samples. Development of in vitro and in vivo models for the design of new therapeutic strategies for CSC population control.
The Research Group on Molecular Therapies is made up of basic and clinical researchers from the Universitat de València, the La Fe University Hospital, the University Clinical Hospital of Valencia, the University Hospital of the Ribera, the National Cancer Research Centre and the Prince Felipe Research Centre.
The multidisciplinary composition of this group, which includes experts in molecular biology, bioinformatics and computational biology, medical oncology, surgery, pathology and new high-throughput technologies (genomics, transcriptomics, proteomics and metabolomics), allows the molecular complexity inherent to human diseases and the search for new therapies from an integrative and translational perspective. This approach is being applied in the different lines of research developed by the group, such as the identification of new biomarkers and molecular targets for the treatment of lung cancer, the physiopathology of pulmonary fibrosis, or the prevention and therapy of hypoxic-ischaemic neuropathies.
The main objective of our research group is to investigate the structural plasticity of the adult brain. We analyze this process at the level of synaptic reorganization, neurite and spine remodeling and neuronal production/incorporation. We are particularly interested in how this structural plasticity is involved in psychiatric disorders, such as schizophrenia and major depression and their treatment. To achieve this objective, we use animal models of these disorders and postmortem material from psychiatric patients. We use different strains of mice expressing fluorescent proteins in selected neuronal populations to visualize structural remodeling, both in fixed tissue and in real time, using organotypic cultures and cerebral windows.
Our group works on different aspects of protein trafficking in plant cells, with special emphasis on functional studies. On the one hand, we try to elucidate the function of a group of proteins (of the p24 family) probably essential in the quality control of protein trafficking in the secretory pathway and in the organisation of the compartments of the early secretory pathway, including the Golgi complex biogenesis. On the other hand, we are interested in investigating the molecular basis of the polar localisation of the auxin transporter PIN1, which determines the polar transport of auxins and is essential for plant growth and development, defining its global polarity.
The research group in Public Opinión and Elections aims at analyzing, studying and finding solutions to all issues and questions related to electoral processes and/or the measurement and monitoring of public opinion, applying the most advanced quantitative techniques.
The most relevant research fields of the group include (but are not limited to) the following: the generation of electoral predictions, inference of individual voting behavior, analysis of polls and surveys, the search of new methodological approaches to improve (reducing costs) the quality of sampling methods, semantic analysis of opinions and monitoring of the internet sentiment, the study of the consequences of non-response and of the biases introduced during the whole inference process, the solution to the gaps in the databases, the integration and pooling of local and global information to obtain multilevel responses, and the development of statistcal theory and methodology.
The approach used in the research group in Public Opinión and Elections is open, not being limited by any particular methodological tendency, and makes extensive use of whatever sources of information. Thus, we use classical and Bayesian techniques, we apply from simple linear regression models to complex approaches based on neural networks, wavelets or auto-binomial models, we use the spatial and/or temporal component of the data explicitly, we perform simulation via Markov chain Monte Carlo or directly by Monte Carlo methods, and we introduce in our models survey data, reported election results, news reports, internet messages and/or official statistics.
The members of the group are open to working with other research groups, companies and institutions and encourage interested parties to contact us in order to explore possible avenues of collaboration.
We are interested in the characterization of mobile internal signals controlling flowering in plants. We have used Arabidopsis thaliana to characterize metabolic changes associated with floral transition by using a metabolomics and lipidomics approach. These approaches have identified a number of metabolic pathways that are altered in plants that undergo floral transition compared to those that remain in a vegetative phase. We are currently investigating the contribution of those pathways to the control of flowering time in Arabidopsis and exploring the possibility that these represent conserved pathways that are important for the control of this trait in cultivated species. This study has been complemented with a transcriptomic analysis which shows which genes regulating those metabolic pathways increase or decrease their expression level during floral transition.
The integration of metabolic, lipidomic and transcriptomic data has provided us with a robust set of information to unravel new layers of complexity in the control of flowering. Recently, we have also developed a quantitative proteomics approach to identify phloem specific proteins and peptides that could represent mobiles signals controlling not only flowering but also other developmental processes. We have already identified more than 100 phloem proteins and we are characterizing their function and their potential role as developmental regulators.
The group Symbiosis, Diversity and Evolution in Lichens and Plants: Biotechnology and Innovation has been developing its research activity since 1986. The 4 central axes of our research are the following:
- Lichens and microalgae: Biodiversity and biogeography. We study the different biotechnological applications, the molecular biology of fungi and symbiont algae. HTS techniques are applied in DNA sequencing of chloroplasts, mitochondria and nuclei. Transcriptomics and Proteomics. Research on Lichen Microalgae studies especially ultrastructural, genetic and functional diversity as well as molecular response to adverse conditions and evolutionary patterns. New molecular markers are developed for the identification of microalgae and for applications to their phylogeny and evolution as well as the development of techniques for mass bioproduction of lichenic microalgae. Techniques of ultrastructural analysis of algae, lichens and plants are used, such as: MO, TEM, SEM and Confocal. Study of the ecophysiology of lichens, microalgae, plants and agricultural crops with applications in Bioclimatology (bioindication analysis of environmental conditions and atmospheric pollution), in the conservation of natural spaces and for the detection of areas at environmental risk. Study of the phenomenon of biodeterioration caused by micro-organisms and study of possible palliative remedies. Cork research focuses on the ultra-structural characterisation of the radial growth and density of cork, with a patent to certify its "quality". Development of lichen bio-indicators to predict cork quality and tree characteristics.
- Massive sequencing of vascular plant chloroplasts: Chloroplast genome of a wild Mediterranean plant in the Iberian Peninsula of the species Arbutus unedo, the strawberry tree of the family Ericaceae. Study of biotechnological applications to dehydration, radiation and temperature stress in crops.
- Evolutionary biology of plants: Research on various species and with a variety of objectives, both basic and applied research. Basic research integrates different types of characters (morphological, anatomical, karyological, palynological, reproductive and molecular) to establish the evolutionary patterns of various groups of plants. The specific objectives of this research are the biosystematic and phylogenetic study of various plant groups. The analysis of the genetic variability of endangered plants and its application to their conservation and the management of their populations is also addressed. Study of the reproductive system of various species with the aim of understanding the patterns of genetic variability in Mediterranean scrublands and their spatial distribution. Conservation of endemic and/or threatened plant species. Study of populations and their genetic variability. Study of threatened flora. Development of molecular markers applied to population biology and plant biosystematics. Study of genetic variability, biosystematics and phylogeny. Finally, in this area, research is carried out on the phylogeography of Mediterranean plants, their genetic variability and migratory routes.
- Microbiomes (bacteria and yeasts) in lichen thalli: Study of their possible biotechnological applications. Isolation and taxonomic characterisation and functional activities of bacteria and yeasts associated with lichens: Contribution to the functioning of lichen symbioses. The group carries out this research and maintains close scientific collaboration with entities such as the Jardí Botànic; the Plant Physiology group "Plant responses to stress conditions" of the UAH; the "Agroforestry Ecosystems" group of the UPV; the "Conservation and Biodiversity" group of the URJC; the Plant Genetics Research Unit of the Missouri University; and the Institute of Biology of the UNAM (Mexico). He also maintains close scientific collaboration with other European and American researchers.
Industrial yeasts, responsible for biotechnological processes, are highly specialised organisms that have evolved under restrictive environmental conditions in different environments manipulated by humans. Our group is interested in understanding the mechanisms involved in their adaptation, which have shaped the yeast genome conferring them properties of biotechnological interest. Different "omics" approaches and evolutionary analysis are used to understand the mechanisms of adaptation to environmental and nutritional changes (temperature, availability of nitrogen and iron, etc.) of yeasts of industrial interest. This research is applicable to the selection and genetic improvement of new yeast strains of interest in industrial fermentations (wine, beer, cider, etc.) and the production of dietary supplements, by different techniques such as adaptive evolution, hybridisation, or the development of GMOs.
Our working group is interested in understanding the molecular mechanisms involved in the adaptive processes that have shaped the yeast genome, giving them such peculiar properties of biotechnological interest.
The results of our research are applicable to the following topics of interest to industry:
- Application of molecular techniques for the identification and characterisation of yeasts in fermentation processes (mainly wine and beer).
- Selection of starter cultures for use in alcoholic fermentations.
- Yeast breeding by non-GMO techniques such as directed evolution, intra- and inter-specific hybridisation, as well as breeding by genetic engineering (GMOs). These techniques are being applied to wine and brewing yeast breeding to increase glycerol production, to decrease ethanol yield, to improve tolerance to low temperatures, to improve growth under nitrogen limiting conditions, to improve fermentative aroma production and varietal aroma release.
Plants manufacture specialised metabolites that aid in interaction and survival with their environment. These compounds, termed "secondary metabolites", are a rich source of health benefits in human nutrition, and also represent the building blocks in the development of new pharmaceuticals. However, secondary metabolism is limited in occurrence, and some compounds are restricted temporally and spatially to certain taxonomic groups.
Development and secondary metabolism are closely connected processes. Part of this association depends on differential gene expression: while information is instructed and wired into the genome, its regulation and display in certain cell types will ultimately determine the ability to accumulate different metabolites.
The control of secondary metabolism in response to environmental and developmental signals is exerted by transcription factors and transcriptional co-regulators that act on cis-regulatory DNA sequences that determine when, where and how genes are expressed, but also on other types of regulatory proteins and RNAs. At TOMSlab we are interested in the transcriptional regulation of secondary metabolism. This has included genomic analyses of transcription factor families and global gene expression analyses, as well as an interest in systems biology approaches that integrate transcriptomics and metabolomics datasets.
The current focus of the laboratory is the worldwide study of gene regulatory networks controlling phenylpropanoid and isoprenoid metabolism in climacteric and non-climacteric fleshy fruits, such as tomato (Solanum lycopersicum) and grapevine (Vitis vinifera), respectively. We are also interested in several other species that possess potential pharmaceutical properties that make them important for drug discovery and functional food improvement.
Vascular tone depends on circulating vasoactive substances and neurotransmitters released in the vessel wall. Sympathetic tone is a fundamental component of vascular resistance that can be influenced by the presence of an intact endothelium, so it could be involved in pathologies where sympathetic tone is elevated, such as in local spasm and hypertension. From the beginning of the formation of the research group, one of the main objectives has been to lay the foundations for understanding the participation of the endothelium and NO in the nervous and hormonal regulation of blood flow in human arteries and veins in different regions. We have also been able to verify that endothelium and NO release do not have a common pattern in the various vascular beds studied. We have assessed, by indirect methods, basal and induced nitric oxide activity in different vascular beds. Knowledge of the basic mechanisms that relate endothelial factors to the perfusion of various human organs or vascular beds allows us to understand the impact that the endothelial-NO system can have on cardiovascular pathology in humans.
The endothelial modulatory role can be altered in various pathological conditions such as bronchial hyperresponsiveness, arterial hypertension, insulin resistance, hyperthyroidism and obesity among others. These pathologies share several risk factors and can often occur in association. For example, obesity is frequently associated with hypertension and increased sympathetic tone. It is therefore possible that the adrenergic stimulation of resistance arteries is modified as a consequence of an altered release of endothelial factors. The same may be true for the response to substances such as vasopressin, endothelin, thromboxane, angiotensin, which are directly involved in the regulation of circulation.
A few years ago we initiated in vitro studies of the effect of endogenous NO synthase inhibitors on endothelial nitric oxide release and their effects on the endothelium-dependent response to acetylcholine in patients with chronic renal failure and undergoing haemodialysis. We have also been able to verify the correlation between liver dysfunction and increased plasma ADMA concentration. In studies of patients with hepatorenal syndrome (HRS), we have shown elevated levels of ADMA and SDMA and correlations of SDMA with levels of renal impairment.
Our experience indicates that the contribution of the endothelium varies in different human vascular beds with varying pathology. Given the logical limitations of human experimentation, our studies in human arteries and veins are performed using in vitro techniques. These studies have many advantages from an experimental point of view, in particular the easy manipulation of vascular samples and the possibility of carrying out pharmacological studies with few limitations. For ethical reasons, studies cannot always be performed on human samples. In these cases we have resorted to different animal models. Recently, the study of vascular effects of new generation drugs has been added, including late sodium current blockers, levamisole interactions with cocaine, insulin degrading enzyme blockers, PPARγ agonists and others.
Studies of vascular reactivity have been completed with analytical determinations by HPLC or colorimetric techniques of substances that can interfere with the endothelial nitric oxide-dependent vasodilator system (NOx, ADMA, SDMA, L-arginine among others) and determinations of protein and gene expression by western blot and PCR techniques.
The research group "Immunology of fungal infections" has focused its research over the last fifteen years on the study of the host immune response to Candida albicans. The group has a multidisciplinary background, both in Microbiology and Immunology, so it has an ideal profile to study the interactions between pathogenic fungi and cells of the immune system both in vitro and in vivo. Although the research conducted is primarily basic in nature, it has clear applied potential in the development of new immunotherapeutic approaches for the treatment of fungal infections.
C. albicans is an opportunistic pathogen that, depending on the underlying host defect, is capable of causing a variety of infections ranging from superficial mucocutaneous candidiasis to severe invasive candidiasis. The frequency and severity of the latter has increased considerably in recent decades, due to the increase in the at-risk population that is immunocompromised or weakened by various causes.
Resistance to candidiasis requires the coordinated action of innate and acquired immune defences. Mature cells of the innate immune system use different PRRs (pattern recognition receptors) to directly recognise MAMPs (molecular patterns associated with micro-organisms), so that with a limited number of these receptors they can recognise a wide range of pathogens. The most important families of PRRs in C. albicans recognition are Toll-like receptors (TLRs) and C-type lectins (CLRs, such as dectin-1). In this context, our group demonstrated that the TLR2 receptor is involved in the recognition of C. albicans, both yeast and hyphae, inducing cytokine and chemokine secretion through a pathway dependent on the adaptor molecule MyD88 and that such recognition is critical for protection against invasive candidiasis in a mouse model of infection.
In 2006 it was described that haematopoietic stem and progenitor cells (HSPCs), from which all immune system cells are derived, express functional TLRs, and that signalling via TLRs in haematopoietic stem cells (HSCs) triggers their entry into the cell cycle and their differentiation into the myeloid lineage. This discovery opened new perspectives on pathogen-host interactions, as these receptors could be involved in modulating haematopoiesis in response to micro-organisms during infection. At that time our group decided to study the involvement of PRRs in the interaction of C. albicans with HSPCs and its consequences for the resolution of the infection. Working along these lines, we have shown that C. albicans induces the proliferation of HSPCs and their differentiation towards the myeloid lineage, both in vitro and in vivo. This response requires signalling via TLR2 and dectin-1, and results in functional macrophages that are able to internalise and destroy yeast, as well as secrete inflammatory cytokines. These results indicate that pathogens can be directly recognised by HSPCs through PRRs, thereby promoting the replenishment capacity of the innate immune system during infection. These receptors may therefore be at least partly responsible for the emergency myelopoiesis that occurs during most infections, including invasive candidiasis.
On the other hand, numerous recent studies have challenged the dogma that immunological memory is an exclusive feature of specific immunity, as cells of innate immunity can exhibit some "memory" and respond differently to a second encounter with the same or another microbial stimulus. For example, exposure of monocytes and macrophages to C. albicans increases their response to a second encounter (trained, dectin-1-dependent immunity), while TLR4 or TLR2 ligands confer a reduced inflammatory response to macrophages (tolerance).
In parallel to the studies on the memory of innate immunity, our group set itself the new goal of studying the function of phagocytes formed after HSPCs contact with microbial ligands. Using in vitro and in vivo models, we have shown that stimulation of PRRs in HSPCs affects the functional phenotype of the macrophages they subsequently generate. Therefore, our results show that this new concept of "memory" of innate immunity can be applied not only to mature myeloid cells, but also to HSPCs, which contributes to increase the durability of innate memory over time.
Based on these results, and those of other authors in the same line, an active role is now assigned to HSPCs in the fight against infection. The hypothesis we are currently working on is that HSPCs can directly detect microorganisms and contribute to protection against infection by different mechanisms, including their ability to differentiate into myeloid cells with an enhanced phenotype to confront the pathogen and initiate the immune response.
The results already obtained open up new perspectives, which may be of great interest at the intersection between Immunology, Microbiology and Haematology. The existence of new mechanisms in the host-pathogen interaction, and their consequences in modulating the immune response during infection, may represent a new target for intervention against serious infections by enhancing the immune response. In addition, modulation of haematopoiesis by microorganisms could reveal new strategies for the treatment of diseases with alterations in myeloid cell production, such as myeloid leukaemias.
Research in endocrine surgery, bariatric/metabolic surgery, coloproctology, hepato-biliary surgery, pancreatic surgery, oesophago-gastric surgery, abdominal wall surgery, breast surgery.
The UIRFIDE research group has been working since 1995 in the 3 main classic lines that make up the world of physical and sporting performance. Sport and Physical Activity Management, where research is carried out and specific interventions are proposed on problems such as those related to the quality of sports services or event management (from small local events to large international events).
Sports Performance, where again research is carried out and interventions are proposed related to the needs of athletes with a view to improving their performance, whatever their starting level and their stage of development.
And finally, on the world of Physical Activity and Health, focusing especially on those populations with greater adaptation needs in physical and sporting practice, such as older adults or people with disabilities.
Our research group is made up of two researchers of the staff of the Universitat de València. Marcel·lí del Olmo Muñoz is University Professor and carries out his academic and research activity in the Department of Biochemistry and Molecular Biology. He has obtained 4 tranches of evaluation of research activity to date. His research has been mainly linked to the yeast S. cerevisiae, covering aspects such as DNA and chromatin structure, regulation of gene expression, polyadenylation and transcription termination, as well as applications of this microorganism in biotechnological processes such as wine and bioethanol production or biocatalysis. He has carried out research stays at the Institut für Zellbiologie (ETH-Hönggerberg, Zurich) and at Tufts University (Boston).
Cecilia Andreu Masiá is Associate Professor in the Department of Organic Chemistry at UVEG. She did her postdoctoral stay at the Department of Chemistry of the Massachusetts Institute of Technology. Her research activity has been developed in several fields: asymmetric synthesis with enzymes in organic solvents, supramolecular chemistry studies of reaction mechanisms, biological chemistry (synthesis of peptides and their applications as therapeutic agents and in organocatalysis processes, as well as in the use of yeasts as biocatalysts in stereoselective synthesis). She has obtained four tranches of research activity evaluation.
Over the last few years, the research of both researchers has progressively converged so that they now form an independent research group whose main objective is the development of biotechnological applications of yeasts in different fields. Specifically, we have worked together on projects of different nature: characterisation of peptides with antimicrobial activity; use of yeast for the generation of chiral synthons precursors of compounds of pharmaceutical and industrial interest and development and improvement of the "Yeast Surface Display" methodology for the exposure of certain peptides and proteins on the cell surface and analysis of the biotechnological relevance of this technique. All this work has resulted in 12 publications in mainly 1st quartile international journals since 2010. At present, the research group continues to deepen these lines of work.
