The research carried out by the group, which was set up over 20 years ago within the Differential Geometry of Surfaces, is closely related with different physical problems, as well as with certain variation and optimization problems, both in differential and convex geometry. It is well known that, in mathematics, physics and biology, there is a wide range of problems and phenomena in which the theory of curves and surfaces plays a key role.
The major part of these phenomena clearly and decisively involve so-called “extrinsic geometry” of the surface, which in intuitive terms is the surface geometry perceived from its outer part, and which is measured by means of its “mean curvature”. Two popular examples of these phenomena are soap films and capillarity surfaces. Others, which are more theoretical and complex, are related to physical phenomena as diverse as relativistic particles, black holes, gravitational waves or the bosonic string theory. On the other hand, one of the main problems in convex geometry is to determine the convex bodies which maximize or minimize a specific geometric parameter such as, for instance, the surface area or volume, when two other such measurements are prescribed, such as diameter, width, circumradius or inradius. This kind of problem, which has its roots in the classical isoperimetric problem, may have diverse applications, such as establishing optimum packing or determining specific configurations.
Within this framework, in recent years the group has been working in different research areas, which can be divided into two main branches: “Variation Problems in Differential Geometry and Sub-varieties” (issues as diverse as the study of the existence and uniqueness of spatial hypersurfaces of constant mean curvature in Lorentzian space-times; stability index of hypersurfaces with constant mean curvature in spheres; study of helicoidal configurations in the environment and “Optimization Problems in Convexity and Discrete Geometry” (roots of the Steiner Polynomial and their relationship with other classical problems, such as the Blaschke problem, the Hadwiger problem and the Teissier problem, as well as the study of optimization problems with constrained optimization in grids ).
Hypersurfaces with constant mean curvature play a vital role when establishing models of the Universe. In particular, it is essential to study the geometry and physics of those huge enigmas the Cosmos holds: black holes. Solar protuberances, which are the manifestation of highly intense magnetic fields stemming from one area of the corona and dying in another one, are modeled geometrically as constant mean curvature tubes whose central curve is a helix. Moreover, it is known that many charged particles under magnetic fields obeying Lorentz law move helicoidally. What is more, helixes are also the trajectories described by many models of relativistic particles. Thus, helicoidal forms, so abundant in the environment, arise, both at the microscopic level (protein chains, the most famous being those forming the DNA of the chromosomes of the cells, nanotechnology, bacterial flagella, etc.) and macroscopic level (climbing plants, animal teeth and horns, seashells, whirlwinds, etc.). In summary, helixes are a basic ingredient in the great universal show and, naturally, we wonder why the helix is such a popular form in nature, in our artistic expression, in our daily life and in the Universe.
The packing theorem has stirred up the interest of scientists for centuries, and more recently the interest of scientists of diverse disciplines, due to its application to a wide range of problems in physics, chemistry, biology and even cryptography and code theory. Another area of special relevance in convexity is Geometric Tomography, that is to say, the reconstruction of a body through the study of its sections and projections. Its application to medicine (X ray, CATs, scanners…) currently makes it an important research branch.
Regarding the collaborations with national research groups, we would like to highlight the ongoing alliances with the Universities of Granada, Sevilla, Valencia, Jaume I in Castellón, Alicante, Miguel Hernández in Elche and Polytechnic of Cartagena. Internationally speaking, the Group working on Differential and Convex Geometry has collaborated with the Federal University of Ceará, Federal of Espíritu Santo and IMPA (Brazil), University of El Valle (Colombia), University of Paris VII (France), Catholic University of Loven (Belgium), Polytechnic and Catholic University of Milan (Italy) and University of Magdeburg (Germany).
“One of the main problems in convex geometry is to determine the convex bodies which maximize or minimize a certain geometric parameter (e.g. the surface area or volume) when two other such parameters, like diameter or width, are prescribed”.
Obtaining new enzymes of industrial interest through cloning, overexpression and molecular evolution, has allowed the Group to achieve the detailed knowledge of the structure-function relationship and its application in biotechnology. In another respect, different antioxidants have been characterized both as bioactive compounds and as enhancing agents of their effect and their lability against the effect of diverse enzymes.
The Group, established in 1986, is currently focused on two research lines: one about the generation of new enzymes/proteins for industrial application through directed and metagenomic evolution and another focused on obtaining and characterizing bioactive compounds with a high antioxidant capacity.
Enzymes are proteins that catalyze chemical reactions in living beings. They are extremely efficient as catalysts and, generally, very selective when choosing the substrates they eventually turn into products, often being stereospecific. From an industrial point of view, they are key tools for the so-called green chemistry. Enzymes, having evolved in nature under high water activity conditions, neutral pH and physiologic temperature, are not generally adapted to industrial environments, which are characterized by the use of organic solvents, extreme pH, high temperatures or a high saline concentration.
Finding new enzymes adapted to the necessary conditions for their industrial use might be carried out through metagenomics, a technique establishing libraries of all the genomic DNA found in an ecosystem, without the need to cultivate the microorganisms present; this enables access to a large bank of genetic diversity, especially of hostile environments, such as those with extreme temperatures (thermal springs), high salinity or extreme pH, since 99% of the organisms living in these environments are uncultivable by means of the classic microbiological techniques. It is also possible to adapt known enzymes to an industrial environment through the use of directed evolution techniques. This biotechnology area is based on simulating the driving force of natural evolution (pressure-selection) in the laboratory (in vitro). Thus, the proteins/enzymes might be improved in their specific activity, thermostability, regioselectivity and stereoselectivity, adaptation to organic media, or even generation of new enzymatic activities. Both processes (metagenomics and/or directed evolution) generate a high number of variants per library which are analyzed by means of high process capacity robotic systems.
Research by this Group, using both molecular technologies, has enabled a new enzyme to be obtained, i.e. acetil xilan esterase, capable of deacetylating cephalosporin C which may be integrated in the industrial processes of semisynthetic antibiotics synthesis and adapted glycine oxidase for use as D-amino acids substrate of great industrial interest. Likewise, carboxylesterase has been obtained which acts in highly alkaline environments and two S-adenosylhomocysteine hydrolase which synthesize S-adenosylhomocysteine under industrial conditions. The Group is working on this line in collaboration with Professor Takami (Japan Marine Science and Technology Centre) on microorganism enzymes in extreme marine environments. This collaboration has generated several scientific publications. Likewise, there is an active collaboration with Professor Golyshin (Bangor University, UK) in metagenomic works. In the field of new enzyme/protein generation, three contracts with Sanchidrian 18 and one with Seprox Biotech have been entered into.
Regarding the second research line opened by the Group (the obtaining and characterization of highly antioxidant bioactive compounds), we must first explain that an antioxidant is a molecule capable of delaying or preventing the oxidation of different compounds, thus of major interest for the food or pharmaceutical industries, as is the case of fatty acids, vitamins, phenols, etc. Moreover, at a biological level, antioxidants inhibit the oxidative stress, phenomenon related to the development of a wide range of diseases, including Alzheimer’s, Parkinson’s, diabetes, rheumatoid arthritis or cardiovascular diseases. Due to these reasons, the use of molecular antioxidants as dietetic ingredients or as nutraceuticals in functional food has gained great interest in recent years.
This research group has recently succeeded in the synthesis and characterization of different compounds belonging to two vast families of bioactive compounds with a high antioxidant capacity: stilbenes and betalains. Moreover, it has managed to establish the relationship between their structure and antioxidant capacity, which has represented progress in the knowledge of these bioactive molecules. One of the results of this research has been the discovery of the antioxidant capacity of betalamic acid (basic unit of betalains), resulting in a patent for the obtaining and use of betalamic acid as an antioxidant molecule. Nevertheless, these kinds of antioxidants show two great problems when used by the food or pharmaceutical industries. On the one hand, they show a great lability in the presence of different pro-oxidant agents, as is the case of oxidative enzymes or different pH and temperature conditions. This fact has been disclosed through the publication of different works addressing the oxidation of resveratrol by lipoxygenase or of dopamine-betaxanthin by tyrosinase. On the one hand, some antioxidants show a low solubility in water, which results in a low biodisponibility. This team has solved these problems through molecular encapsulation of different stilbenes, such as resveratrol, pterostilbene or pinosylvin with different kinds of cyclodextrins, both natural and modified.
“The Enzyme Biochemistry and Biotechnology Group has managed to synthesize and characterize different compounds belonging to two vast bioactive families with a high antioxidant capacity: stilbenes and betalains.”
This Research Group forms part of the Department of Cell Biology and Histology of the Medicine College of the University of Murcia. Its researchers are focused on two main lines: on the one hand intracellular traffic and on the other gamete biogenesis, composition and structural organization.
In the area of intracellular traffic, the team intends to know the mechanisms operating in the inner part of the cell, which allow newly synthesized proteins and lipids to be directed from the endoplasmic reticulum to their final destination. The mammalian cells are internally divided into different structures (organelles or compartments) whose organization and function depend on the proteins and lipids constituting them. There are complex transport routes in the inner part of the cell in charge of carrying the different cell components from where they are synthesized to their final location. In order to carry out this process, the cell has a series of elements called transport intermediates or transporters which are continuously collecting molecules and unloading the transported material in specific places of the cell. These transport pathways depend on the cytoskeleton, which is the highway of intracellular communication. The whole process is highly regulated; thus, there is a complex system that ensures the formation, function and maintenance of these transporters. In particular, the Group analyzes the molecular machinery regulating the formation and dynamics of these transport intermediaries operating in the cell routes. Through different experimental models and methodological approaches, it is intended, as a final objective, to elaborate a theory explaining how these transport intermediaries work in the different stages of intracellular traffic. Another goal of is to understand how this transport is altered by certain pathologies. In the case of neurodegenerative diseases, such as Parkinson or Alzheimer, as well as in alcoholic patients, an improper function of these cell transport routes has been reported, leading to neuronal dysfunction. These alterations in neuronal intracellular transport are the origin of these diseases. The Group is optimizing the cell models of these pathologies to know in detail which specific stages and molecules are altered. The final aim of this study is to find repair mechanisms of the damages induced by these pathologies at a cellular level.
The other research line (biogenesis, composition and structural organization of gametes), is based on the fact that sterility among couples has become one of the most important problems in current society. The knowledge at a cellular and molecular level of the fertilisation process in human beings and other species will allow us to understand pathologies affecting gametes, being one of the causes of fertilization failure. The ovule-sperm recognition is a key point in reproduction. In this process, sugars and their receptors play an important role, complementing each other, since each one is located in a different gamete. The Group studies the glycoprotein located in the layer around the oocyte, known as pellucid zone, and their specific receptors located in the plasma membrane of the spermatozoon. This work is being carried out using human material obtained from in vitro fertilisation treatments, with samples obtained from different mammalian species and cultured cells expressing different biologically active proteins in the pellucid zone. In addition, amphibian gamete samples are collected, these being a privileged model since, on the one hand, they produce a great number of oocytes and, on the other, spermatozoa are simultaneously developed in cysts, so that inside each cyst all the spermatozoa are at the same stage of development. The final aim is to identify the molecular mechanisms involved in the recognition and interaction between spermatozoa and oocytes in human beings and other animal species. The Group is also analyzing the dynamics and cell regulation of spermatogenesis, namely, the formation of the sperm in the testicle. As a result of these studies, it has been discovered that the pellucid zone of many species is formed by four glycoproteins, not by three, as formerly believed. The genetic analysis of these glycoproteins in different mammalian species also allows the performance of evolutionary studies. Likewise, it is being studied how ageing affects the testicle structure in animal models, producing cell deterioration and death of Leydig cells which produce the testosterone hormone.
A wide range of morphological and biochemical techniques are being used for the development of these two research lines: confocal microscopy in live cells, immunohistochemistry, electronic microscopy, ultrastructural cryoimmunohistochemistry, electrophoresis and immunoblotting, molecular biology, recombining proteins, proteomics, etc.
These techniques allow us to visualize subcellular structures, even in living cells and, moreover, to analyze their components. The results obtained have been published in prestigious international journals such as Proceedings of the National Academy Sciences, USA, Reproduction and Development, Histology and Histopathology, etc. They have also been presented in national and international congresses.
The deep knowledge of the mechanisms developed in cells is the basis for the development of new strategies allowing its application in a certain biological process and the solution of a specific problem. This means that the basic research performed by the Group is at the service of applied research. All these research works basically intend to understand cell and tissue physiology.
The Group frequently collaborates with other groups and enterprises. Pilar Coy and Manuel Avilés have patented a method to increase monospermy in in vitro fertilization.
“The detailed knowledge of the mechanisms regulating normal cell behaviour provides the team with vital information allowing it to analyze cells behaving abnormally.”
The importance of an adequate water supply during cultivation, as well as during the last days before the harvest has also been identified, since too much water results in lettuce quality deterioration and its higher susceptibility to browning during its useful life as ready-to-eat food.
The lack of water is one of the more recurrent problems of the summer fruit production sector due to the summer drought typical of Mediterranean climate. Some techniques are being studied to lessen the hydric shortage and its consequences, for instance the Controlled Deficit Irrigation (CDI). Peaches have antioxidant constituents, such as different phenolic compounds, in addition to having a moderate vitamin quantity, especially vitamin C and carotenoids, with a provitamin A activity. Generally, the Controlled Deficit Irrigation increased the vitamin C content in peaches, without affecting the rest of antioxidant compounds.
The quality of the irrigation water available in the Region of Murcia imposes an abiotic stress (saline) affecting the phytochemical composition, nutritional value and commercial quality of broccoli. The application of a controlled level of abiotic stress might be useful to enrich broccoli with bioactive constituents, guaranteeing that the subproduct exploitation is industrially useful.
The Group, on the other hand, has designed new functional drinks, based on lemon juice with the addition of natural polyphenolic concentrate of chockeberries, which enhances its antioxidant properties and enriches its contents in bioactive elements. Drinking juice of these characteristics increases the availability of the citric flavonoids without affecting the anthocyanin pigments. Likewise, it improves the organoleptic characteristics of lemon juice.
Another line of research evaluates specific polyphenol activity in vascular function and in gastrointestinal tract diseases, such as inflammation and colon cancer, by means of in vitro experiments, in model animals and interventilation studies in humans.
Moreover, the Group has also evaluated the effects of a stilbene-enriched grape extract in the vascular function of healthy individuals and people suffering from a cardiovascular pathology. Resveratrol-enriched grape extracts (Revidox®) have been developed, demonstrating their anti-inflammatory activity. The results also show a preventive activity in colon cancer and healthy cardio effects. Based on these grape extracts, a study is being carried out on swine together with a clinical trial on cardiovascular patients (in collaboration with the Morales Meseguer Hospital). Although the results are not yet final, the preliminary findings indicate that these extracts exert a positive effect on the heart.
Another line of research has shown for the first time that pomegranates have an anti-inflammatory effect on inflammatory intestinal diseases. The results also show their preventive effect against colon cancer. The activity is mainly due to the formation of substances (urolines) produced by the intestinal flora from constituents which are abundant in pomegranates, i.e. ellagitannins (also present in other food such as strawberries, raspberries and walnuts). In a trial conducted on benign hyperplasia or prostate cancer patients (in collaboration with the Reina Sofía Hospital), it has been demonstrated that after drinking pomegranate or walnut juice, these substances (urolines) reach the prostate and play an anti-carcinogenic and anti-inflammatory role.
Likewise, the effect of a drink enriched with flavonoids and anthocyanins on the metabolic syndrome has been assessed. A clinical trial for the validation of these beverages has been carried out over a period of four months on patients suffering from “metabolic syndrome”, a group of cardiovascular ailments and problems which can affect the oxidative state of adults and post-menopausal women, increasingly frequent in the Region of Murcia. The results are in the clinical and statistical evaluation phase.
Another research line initiated focuses on the use of nutrigenomic tools in the study of the relevant metabolites in vivo in biological activity. Nutritranscriptomics has been used for the multiple analysis of gene and protein expression in diverse human cellular models in vitro, animal models and human volunteers (healthy and ill), in relation to degenerative pathologies associated to chronic inflammation, arteriosclerosis and cancer. The analysis of genetic and protein expression in animal and mononuclear tissues (swine lymphocytes) makes it possible to study how the consumption of phenolic compounds in fruit and vegetables can be associated to effects at a molecular level in vivo and provides information about the possible biological functions and molecular targets that could be affected or modulated by the consumption of food enriched with these compounds.
The work program of this Group has a basic research component, aimed at shedding light on some natural mechanisms that mediate the action of the immune system in states of health and illness. Therefore it endeavours to study what is commonly known as "the body’s defences.” These defences involve components of the immune system able to reach all parts of the human body, to ultimately protect against disease by constant vigilance, preventing harmful elements such as bacteria, viruses, pollens, etc., from entering the body and causing illness, or they deal with their disposal, when such harmful agents manage to cross the natural barriers. The most important issue is the ability of this system to reconcile defence against the strange and harmful, without being aggressive towards the body’s own components that maintain the functional balance of the body.
These complex defence mechanisms can undergo changes that promote the emergence of disease, produced by loss of organism equilibrium, either due to a state of hyperfunctioning of defence systems, which leads to the appearance of diseases caused by excessive activity, such as allergic reactions (rhinitis, asthma, etc.) or to a wide range of so-called autoimmune diseases, frequently in the form of numerous rheumatic diseases (arthritis, lupus, etc.) or autoimmune thyroid or digestive tract (ulcerative colitis, autoimmune hepatitis and Crohn's disease). All of which, given their frequency, have a great impact on health systems, not only in terms of the loss of patients’ quality of life, but also because they require chronic treatment and are a frequent cause prolonged sick leave. Similarly, all lead to a major increase in healthcare expenditure. Furthermore, in the case of transplants, rejections are also the result of excessive activation of the immune defences, which are triggered by the presence of transplants in the body.
Conversely, other diseases are caused a functional default of the defence system, which is expressed as low-capacity defence, involving a lack of "immune surveillance" and a diminished response to aggression by infectious or other harmful agents. The consequence is the increase in infectious diseases, cancer and tumour progression or the deterioration of the functioning of one's own immune system, usually a defect or malfunction, such as either primary or acquired immunodeficiency.
This research team is working to shed light on what triggers both types of defect because such knowledge is of great interest in health sciences. Above all, the Group is endeavouring to clarify the mechanisms that positively or negatively regulate these dysfunctions in the immune system, which are classified under the term "immune processes and immunoregulation". In the first case, many of the studies focus on discovering how an individual responds to something as strange as the implantation of an organ or cells (in the case of bone marrow), with a view to its application to improve donor-recipient selection so they are more compatible, or the use of drugs that reduce the strong response of our defence mechanisms. In both cases the ultimate goal is to improve the acceptance of organ transplants and reduce the processes involved in allergy and autoimmune diseases. In the second case, the objective is to know why certain people and even families are more prone than others to cancer or infections (particularly melanoma or viral infections) and discover whether this is due to defective functioning of the immune system or loss of appropriate defence mechanisms. In this case, the goal of the research is to access mechanisms that can trigger the elements that are necessary to defend the body properly in a specific and controlled way. In any case, research conducted by the Group as an element of basic research seeks to unravel new mechanisms that are essential for the normal functioning of the body’s defences and, in terms of the clinically applied research component, the Group aims to find better diagnosis, prognosis and treatment of the aforementioned diseases.
The Group is particularly interested in areas with high impact on public health and resource optimization in the field of immunology and immune tolerance in transplantation in search of a better use of donated organs and the future availability of less harmful treatments, control of the defence mechanisms in allergic disorders and autoimmune diseases, to improve the quality of life and treatments for these patients, to boost their defences against cancer and infections.
The interest of the research program run by this team lies in the potential of improving the following aspects: early diagnosis of aforementioned diseases through the development of non-invasive and easy-to-use methods, thereby improving them and preventing graft rejection in transplants, the most appropriate prognosis and monitoring of these diseases, once established, by searching for new factors that can provide information on disease progression and permit the adoption of individualized treatment guidelines and, finally, knowledge of new mechanisms and key molecules that can be used to develop new drugs or take therapeutic approaches to correct the body's defence dysfunctions without being accompanied by undesirable side effects.
The primary objective is to contribute to a better understanding of the mechanisms that control the body's defences and the processes of tolerance or reactivity associated with normal functioning of the immune system, with a view to modulating them when they are altered and cause disease.
University of Murcia
Metal ion complexes play a fundamental role in many biological systems. Thus, it is well known that the presence of sodium, potassium, magnesium, calcium or zinc ions for instance in the organism, is essential for human beings. On the other hand, some metal cations, such as the ions of heavy metals, such as plumb, mercury, cadmium, etc. also play an important role in the environment due to their high toxicity, since their accumulation in soil and water means that they are passed on to plants and fish and therefore to the food chain. As a consequence, this provokes the accumulation in the human body, in harmful doses to health, and that is why their detection and elimination from the environment is also a highly interesting research area from a social point of view.
On the other hand, anions are also essential species for maintaining life. It would not be an exaggeration to affirm that the recognition, transport or transformation of some kind of anion is somehow involved in almost every biochemical process. Moreover, as in the case of metal cations, other types of anions behave as environmental pollution agents, thus being harmful for human beings.
One of the main objectives of this Research Group is the development of new types of chemical sensors or species capable of selectively and quickly, easily and effectively detecting the presence of this kind of substrate or analyte, of a cation, anion or neutral nature, interesting both for their implication in biological and clinical processes and for being environmental pollution agents.
The recognition process of the analyte by the new receptor molecules, designed to be the sensors of these analytes, may only be achieved if the relevant receptor meets the principles of complementarity with the substrate and pre-organization of its structure so the binding centres remain properly disposed and the receptor-substrate merger is as effective as possible. In other words, the effective binding between the two species, receptor and substrate, needs the receptor and substrate binding centres to be complementary in size and shape. Moreover, to achieve this maximum complementarity and therefore that the receptor-substrate binding is as steady as possible, the receptor should not undergo any conformational change in its structure, or at least, this ought to be minimal. Figure one shows the selectivity in the recognition of a single analyte, among several, due to the complementarity between the recognition unit and this analyte or substrate.
The work developed by this Research Group is framed within this general context; it should be performed in three clearly different stages.
In the first stage, the design of the chemical sensor molecule or synthetic receptor to be prepared is approached, taking into account it should comprise two unit types: one, responsible for the recognition of the substrate or analyte (recognition unit) and another (signalling unit or antenna) responsible for indicating and marking, through a clearly visible change of a certain property (change in colour, fluorescence, redox potential, etc.), that the recognition phenomenon has taken place (see figure 1). Once the marking and recognition subunits with adequate characteristics to reach a certain objective has been chosen, the next step is to synthesize the specific sensor through the covalent union of these subunits by means of the application of appropriate methodology synthesis and the correct reactives. In some cases, a single recognition unit presents specific properties also allowing it, simultaneously, to act as a signalling unit.
The recognition units chosen for the detection of metal ions, especially heavy metal ions, have as a common characteristic the existence of a nitrogen atom, capable of coordinating these metal ions. It belongs to different types of azadien, azine or azaheterocycle-type subunits of a different nature. Nonetheless, NH groups have been used as anion recognition centres, present in substances such as urea, tiourea, guanidine, imidazole, etc.
Regarding the most commonly used signalling units in this work, the following should be highlighted: the ferrocene unit, due to its known redox character, and pirene or anthracene, because of their fluorescent properties. The confirmation that the synthesis has led the designed structure correctly is carried out by means of the utilization of conventional spectrometry techniques for structural determination (nuclear magnetic resonance, mass spectrometry, etc.).
Once these molecules have been designed and synthesized, a second work stage addresses the study of the sensor efficiency, in solution, through the determination of its selectivity against a specific analyte in presence of others, with the subsequent measure of the receptor-substrate association constant (Kas) and the stoichiometry, or receptor/substrate relation with which the recognition process is produced. In addition, it the sensibility of the sensor detecting the analyte is also determined, through measurement of the detection limit, understood as the minimum substrate or analyte concentration detected with this receptor.
If the results obtained in the previous stages are appropriate, the last stage addresses the manufacture of an easy-to-handle device, by anchoring the molecular sensor in different types of solid media (cellulose, siliceous, polycarbonates, beta-cyclodextrins…).
“The Group currently owns a patent in force on a “method for the functionalization of a substrate, functionalized substrate and the device containing it””.
Thrombosis is one of the diseases with a high prevention success rate. Prevention is based on the widespread use of oral anticoagulants – such as heparins or acenocumarol, the latter being taken by approximately 1.3% of the population. Likewise, this Group is studying other potential medicines, especially those with antithrombin effect, which might constitute an alternative treatment to thrombosis. This research phase is all about learning how these medicines act and interact with other coagulation factors.
This Group’s research activity aims to transfer laboratory findings to the field of medical care, that is to say, to transfer the results of medical research to specific areas of health care. Hence importance is placed both on the Group’s collaboration with health workers, directly involved in medical care, and the dedication of the research staff to teaching and assistance tasks. The best way to transfer knowledge in this area is to avoid a strong division between research and medical dedication. The ultimate goal of both research and assistance tasks is to contribute to improving public health. The concept defining this Group is the lack of separation between basic and clinical medical research, opting instead for useful medical research that is socially relevant and truly multidisciplinary in nature (encompassing medical researchers, biologists, chemists, veterinaries and pharmacists).
Since its foundation in 1991, the Group has been carrying out research in the aforesaid areas of work, and has contributed to the identification and characterization of environmental mechanisms that are involved in the molecular modifications of antithrombin, a decisive risk factor in thrombosis. Likewise, the Group has identified and characterized new molecular modulators responsible for acenocumarol-related anticoagulation rates (pharmacogenomics of oral anticoagulation). Likewise, some flavonoids have been found to play a regulatory role in platelet function, especially via tromboxane generation and some molecular abnormalities have been identified that are responsible for hereditary platelet disorders.
The research Group participates in the Instituto Carlos III RECAVA network, a Cardiovascular Network integrating 21 national groups working in this area. Likewise the Group collaborates regularly with Professor Watson (University of Birmingham), Professor Nursen (University of Burdeaux), Professor Lyp (University of Birmingham) and Professor Alberca (University of Salamanca), among others. It has active research contracts with various enterprises: AMGEN, Johnson and Johnson, Griffols, etc. The Group has several patents (highlighting 200802436: “Human Citrullinated Antithrombin Monoclonal Antibody and its Uses”) and has been awarded many research prizes, among them the Best Scientific Work presented by the Spanish Association for Hematology and Hematotherapy (2007, 2008, 2009), International Prize Martín Villar, awarded to Doctor Javier Corral for the best work published in the field of Homeostasis during 2007 and the Schering Foundation Prize, awarded to Doctor Vicente for the best Spanish work published in an international journal in 2006. Thanks to their participation in the RECAVA network, the Group has published in the Nature Genetics journal, in which they reported their research into abdominal aortic aneurysm with the participation of four Spanish researchers. Among these figure Professor Vicente Vicente and Professor Javier Corral, the coordinator, together with collaborating researchers from 61 renowned North American, Canadian and European centres.
The Group initially furthers studies on image quality evaluation systems and optical aberration measurement, beginning with the development of an asymmetric double-pass system by means of which is possible to register the retinal image of a point. The OQAS system for the evaluation of the optical quality of the eye, fabricated and distributed world-wide by Visiometrics S.L., is based on these works. Shortly after, the Group creates one of the first ocular wavefront sensors, a Hartmann-Shack type, modified later on in collaboration with the University of Rochester to operate in real time (25 Hz) for the first time.
Regarding the knowledge of the sources and location of ocular aberrations, the laboratory has recently revealed novel findings. By comparing the aberrations of the cornea and the eye as a whole, the contributions of the main components of the eye have been separated, finding that the crystalline compensates a great part of the aberrations produced by the first corneal surface. There has been progress in the understanding of the mechanisms responsible for this compensation, which has a purely geometric basis. Another research line aims to understand the changes in ocular optics caused by ageing. A significant deterioration of retinal image quality was discovered, whereas the cornea remained relatively unaltered. This aggravation is mainly due to a progressive change of the aberrations of the crystalline, which is separated from the cornea which is found in young patients’ eyes. To give one an idea of the importance of this work, it should be mentioned that the article published in 2002 is currently the most quoted article (161 quotations) of all those published in the Journal of the Optical Society of America (JOSAA) in the last eight years (more than 2600 articles). This result in basic science was also the basis for the development of new generations of intraocular lenses with negative spherical aberration, somehow copying what occurs in young eyes. These lenses (e.g. the TECNIS lens of AMO, whose development was supported by LO · UM), are nowadays widely used by millions of people subsequent to cataracts surgery. The Group has also developed other more applied aspects in ophthalmic optics, such as the analysis of the optical properties of progressive lenses (in collaboration with ESSILOR International, France), used for the development of new generations of progressive lenses, such as the Varilux Physio model.
As we had robust systems for aberration measurement, it was natural to approach their correction by means of Adaptive Optics Techniques (AO). The first demonstration of a corrective aberration system was achieved in real time and tight loop: a prototype which served as the basis to several generations of optics systems in which high quality deformable mirrors and high resolution liquid crystal modulators are used, most of them devoted to visual simulation.
The Group discovered that the eye behaves as an aplanatic system, reasonably corrected of spherical aberration and coma. Moreover, the optical characteristics of the eye outside the axis (in the periphery) have also been studied in the last years. A reason for this interest has been the possible relationship between these characteristics and the development of myopia. The myopic eye is more far-sighted in the periphery than the emmetropic eye. These results have inspired the design of a new lens which may prevent the development of myopia acting on peripheral refraction.
In the realm of adaptive optics and vision, many studies have been conducted using these tools for the design of new profiles enhancing the depth of the focus, the study of the impact of optical quality in peripheral vision, the effect of the correction of several aberrations in visual quality or the possible neuronal adaptation to the specific optical features of each eye. A recent quantum leap has been the development of a new system of binocular adaptive optics which will be used in studies relating optics induced in both eyes and diverse aspects of binocular vision.
Putting into relation the optics of the eye and vision quality is basic for the development of optimized visual solutions. Experiments have been carried out using adaptive optical systems and other strategies, including the application of optical metrics for the prediction of visual quality. An outstanding result was the demonstration that the optical quality of the eyes of subjects with an excellent visual quality was not exceptional. This suggests that the presence of moderate aberrations does not prevent good vision and has a potential relevance to define the patterns in optimal correction strategies.
The laboratory strives to convert some of its own experimental prototypes into instruments which may be used in clinical environments. It allows studies with a high number of subjects, and eventually may be used in clinical practice, with the subsequent benefit to the patients. The use of different methodologies of computational modelling has allowed the development of new intraocular lenses.
A new research line has been consolidated in recent years. It involves the use and control of ultra-short and ultra-intense-pulse lasers. A multiphoton microscopy used to get ex vivo cornea images has been made available. Control of the wavefront of the laser used has been recently established. The system is operative and provides extraordinary quality images in ocular samples.
The LO·UM clearly wishes to transfer its researches. Diverse members of LO·UM are co-inventors in ten international patents, several of them exploited worldwide by international companies. Moreover, the LO·UM together with the university of Murcia have created a technology based enterprise (Voptica SL) aimed at developing part of the inventions of the laboratory.
“Pioneer in the development of strategies for the study of eye optics, several of the LO’s findings and ideas have been implemented in instruments and devices currently used in optics and ophthalmology. “
Polytechnic University of Cartagena
The Telematics Engineering Research Group (TERG) of the Polytechnic University of Cartagena (UPCT) is formed by 19 full-time professors (15 of them have a PhD), several research scholars funded by national and regional competitive Programmes and many engineers recruited through contracts with enterprises and public and private entities.
The TERG Group has 3 fully equipped R + D laboratories, with a total area of 200 square meters. For the computational and simulation tasks there is a server room with a high performance cluster or group of computers linked by a high speed network.
The Group has a wide experience in the realm of optical and wireless communications, especially in everything regarding cellular systems, WiFi, WiMAX, wireless sensor networks, active and passive RFID (radiofrequency identification) and vehicular networks (vehicle to vehicle communication, vehicle to road infrastructure and vehicle to person). Likewise, it has experience in telecommunication network planning and evaluation, in quality of service in internet, in efficient transmission of contents over electric power distribution networks and in implementation of added value telematic services (tracking, services based on context and environmental intelligence, fleet tracking, etc.), which put in use advanced network functions including technologies such as overlay networks with which is possible, at an application level, to overcome some of the internet deficiencies. Finally, it is worth mentioning that part of the Group members also research lines related to the Ben Arabi supercomputer of the Region of Murcia, in the development of efficient simulators of different network technologies and the planning of extremely high speed interconnections. The Group is also involved in the prospection and development of new communication technologies for the future Oceanographic and Coastal Observatory of the Region of Murcia.
In all the aforementioned areas, the Group offers a number of publications in high-impact journals and lectures in national and international prestige congresses proving the quality of its research.
The Group has worked and is currently working in a cooperation framework with diverse regional, national and international enterprises, underlining the transfer of results to enterprises, thus implying technological innovation and the main role of intellectual property and patent generation. Among those enterprises, to the following should be noted: Inforges, Aquiline Group, Campillo-Palmera Group, Integra Foundation, Navantia, Tissat, Telefónica R+D, Siemens, Inabensa (Abengoa), Robotiker Foundation and many more, with whom shared projects and /or collaboration contracts have been entered into. As a result, both social and technological sectors benefit from the research of the Telematics Engineering Group . This fact can be underlined with a few significant examples of projects undertaken by some of the Group members:
The W2LAN protocol to turn a mobile network 802.11 Ad-Hoc (MANET) into a LAN Ethernet proposes a solution to a technical problem. An immediate application generated by this work is to provide network coverage to a certain area which, for instance, has suffered a natural disaster. It would only require that the rescue teams carry with them wireless units equipped with the W2LAN protocol, without needing to install additional equipment.
The MatPlanWDM tool for the planning of optical networks based on multiplexing by wavelength division is used both in teaching and research. It is currently available to any teacher or national or international researcher through MatLab central, with a high number of visits and downloads.
Register and Analysis of Human Movement through Sensor Systems depicts a solution that, by using certain intelligent elements, allows, among other things, the creation of an application which can be used in the rehabilitation of patients at home or in automated assistance of elderly people and other special social groups (disabled people, children, etc.). This line is of great social interest.
There is also a lengthy list of applications related to logistic improvement in warehouses, vehicle network planning, automatic code generation for sensor networks, networks for coastal communication, etc.
“The Group actively collaborates with other teams from the Universities of Vigo, Carlos III (Madrid), Polytechnic of Catalonia, AGH University of Science and Technology, Cracow, Cornell, USA, and several enterprises: Tissat, Inforges, Ecomovistand, Quobis Networks, Gigle Semiconductor, Arantia 2010, Aquiline, Teltyc Telecommunications, Inabensa, Siemens, Treelogic… and has registered Intellectual Property rights on a software for data sending between WiFi mobile terminals in cooperative mode or relay (SALTA), exploited by Tissat S.A.”
The Research Group works on the compared anatomic and embryologic study of the vertebrate central nervous system. The topic is therefore very wide. The Group studies how this fundamental organ of our body develops (in the sense of how it is built, how its different parts and subpopulations of neurons grow), studying it from a compared perspective, which also reveals how the brain has developed over millions of years, from the simplest initial forms to the current human brain.
Although the Group initially used classical morphological study procedures (histology, histochemistry, immunohistochemistry) and those related to experimental neuroembryology (extirpations, transplants and rotations of the embryonic neural tube; xenotransplants using quail as tissue donor on chicken as the receptor), techniques still used since the 90’s, molecular methods have been introduced enabling the descriptive and experimental study of the expression of the genes controlling neural development. This pioneer activity of the team in the interaction area between molecular biology and neuromorphology has been useful to generate important models of general interest for the understanding of cerebral structure (prosomeric model, rombomeric model, palial subdivision model, subpalial subdivision model). Currently, a new model of the hypothalamic structure is being elaborated.
Essentially, these studies analyze the fields of early-appearing gene expression during brain development, and try to classify the morphological position, either longitudinal or dorsoventral, of these patterns (enlightening the potential causal mechanisms, i.e., experiments to explain why these processes happen), and experiments are conducted to determine the prospective destination of the regions discovered, namely, to see which parts of the adult brain derive from those initial outlines. This development is likewise monitored step by step, discovering how the immature neurons reach their final locations and mature in their neurochemical properties (neurotransmitters, peptides, hormones, receptors) always using the genetic markers, in a exclusive methodological approximation the Group has called “neural genoarchitecture”. Some studies are performed in transgenic mice, which have specific molecular labelling, or in which a gene has been deleted by means of genetic engineering. Eventually, the conclusions obtained in a certain species are comparatively analyzed (in relation to other animal species) to find out if the parts analysed represent common brain elements of all vertebrates or are otherwise new having appeared in a specific evolutionary phase. Genoarchitecture studies usually reveal the cerebral structure with more detail than other approximations, so the findings often throw light on obscure points in our neurobiological and clinical neurological knowledge.
The Group, apart from its relationship with the University of Murcia, is integrated in CIBERER (Centre for Biomedical Network Research on Rare Diseases), dependant on the Carlos III Institute, Ministry for Research and Innovation. As such, the Group addresses essential study topics about the biology of brain development congenital diseases, particularly holoprosencephaly, septodysplasia and Rieger syndrome.
The neuromorphological and neuroembryonic findings achieved by the Group have been gathered in many research articles, revisions and chapters, as well as in a detailed stereotaxic atlas of the chicken brain (the first one ever representing the embryologic origin of the adult neuronal populations), published by three members of the team – L. Puelles, M. Martínez de la Torre, y S. Martínez – in collaboration with the renown Australian experts in cerebral atlas G. Paxinos and C. Watson (Academic Press/Elsevier, 2007). A revolutionary neuroanatomy text for medicine and neurobiology students has also been published (Puelles, Martínez, Martínez de la Torre, 2008; Pan-American Medical Editors). This still incomplete work is already available on internet. Several members of the Group likewise collaborate in the preparation of a public digital atlas of human brain development, made available by the Centre for Life of the University of Newcastle (United Kingdom), in collaboration with two British groups (www.hudsen.org). Currently, L. Puelles is applying his models to produce the reference anatomic atlas Allen Atlas of the Developing Mouse Brain, an important public database of the Allen Institute for Brain Science (Seattle, WA, USA), wherein around 2000 genes are being mapped during the pre and postnatal development of the mouse brain (including the adult phase). This project is available on internet (www.developmentalmouse.brain-map.org), representing a new and significant instrument for the progress of research in this field.
“The Group addresses descriptive type studies, based on mapping gene expression (genomes, human genome and genome of many laboratory animal species). These studies aim to understand the developing brain, which cells express a specific group of genes, what helps to separate and illuminate the areas”.
Centre for Edaphology and Applied Biology of Segura (CEBAS)
Spanish National Research Council (CSIC)
Some of the main contributions of the Research Group fall within the area of axonal regeneration and connectivity, and the demonstration that in the central nervous system of the adult mammal, axons of the central neurons can grow again, reinnervating their usual target territory and re-establishing functional . Another important finding revealed the death pattern induced when the optical nerve, for instance, is injured, and that this death pattern could be modified.
The research of the experimental ophthalmology team has also required, especially recently, every effort in the development of new techniques, such as those for image analysis for the objective and automatic quantification of the retinal ganglion cell population, the thickness of the layers of the retina and the volume of the retinotectal innervation, or the fine-tuning of functional techniques such as pupilometry and full-field electrophysiological register of the retina simultaneously performed in both eyes, as well as the analysis of molecular changes associated with retina lesions.
Since its creation, this Group has been closely related to national and foreign universities, such as the University of Alcalá de Henares (Physiology department. Medicine College), Oregon Health and Sciences University (The Raymond Lund Laboratory, Casey Eye Institute), Uppsala University (Unit for Developmental Neuroscience. Department of Neuroscience. Uppsala Biomedicinska Centrum) or Oxford University (Retinal and Neurobiology Group. The Nuffield Laboratory of Ophthalmology).
The members of the team have likewise collaborated with different pharmaceutical companies, such as Novartis Ophthalmics, and Allergan Biological Sciences, in the early detection of molecules which may have this protector effect, analyzing the effect on the animal lesion models developed by the team.
“The studies on central nervous system lesions, developed by the research team, using the visual system of the adult mammal as a model, has allowed it to understand and corroborate novel findings in the neurobiology of the central nervous system”
Centre for Edaphology and Applied Biology of Segura (CEBAS)
Spanish National Research Council (CSIC)
The research is oriented to the study of the adaptation processes of plants to the adverse conditions of typical Mediterranean areas: drought, soil salinity and irrigation water.