Post-graduate Program in Science and Biotechnology
Research Line 1: Identification Of New Prototypes and Bioactive Molecules of Importance in Biological and Biotechnological Systems
This line includes: a) prospecting bioactive products of synthetic, semi-synthetic or natural origin (eg. snake venom, plants and algae) to characterize their biological activity and therapeutic potential; b) analyzing the function of molecules and macromolecules from various biological systems including physiological (eg. hemostasis, osteogenesis and immune system), pathologic (eg. cancer, thrombosis, viral, bacterial or parasitic) or genetic (eg. polymorphisms) processes using different methodologies and c) generating registers and patent for new bioproducts for treating diseasses of local and/or global importance.
Member: André Lopes Fuly (Permanent)
Project: Bioprospecting properties of molecules with anti-venom serum: potential and prospects.
Description: The Laboratory of Animal Venoms and Toxins Inhibitor and Evaluation (LAVENOTOXI) aims at the investigation of natural products (derived from plant and marine species) and synthetic in the neutralization of biological activities (coagulant, hemorrhagic, proteolytic, edema, myotoxic) venom Brazilian snake, Bothrops jararaca and highlighted Lachesis muta, because the statistics are important species and severity of snakebites in Brazil. The animals snakes are formed by a complex mixture of substances used for both defense and attack, as the digestive function of the prey. In general, the poisons are in the majority, proteins (enzymes) that account for the various toxic and biological effects observed in victims, such as neurotoxic, inflammation, cardiotoxicity, myotoxicity, hemorrhagic, coagulant, hemolytic, hypotensive. In Brazil and elsewhere in the world, the snake bites are a serious problem to society and are considered today by the World Health Organization as a neglected disease. Currently, the treatment recommended by the Ministry of Health for snakebites is the administration of serum obtained by immunization of horses. In general, systemic effects are reversed, but the local effects, not always. And this fact can create a health and economic problem because it leads to tissue destruction resulting in the amputation of the affected limb, thereby increasing the morbidity. Moreover, the serum has disadvantages: it is thermo-labile and its distribution to cities far from major centers is difficult, and can have side effects on the victims (anaphylactic shock, which can progress to death). Thus, alternative treatments are suggested. And in this sense natural products as well as those obtained by organic synthesis are great candidates. In the literature, several studies have reported pharmacological properties to compounds isolated from marine organisms (algae, sponges, anemones) as antibiotic, antifungal, antiviral, antitumor, anticoagulant, antiangiogenic. However, snake venom properties of marine organisms are poorly studied. Therefore, the search in nature (especially of marine organisms) of molecules with biotechnological potential, and therapeutic drug development with potential antidote becomes important. In addition to streamlining the design of molecules obtained by organic synthesis antiophidic to such property, as well as the isolation of proteins from snake venoms and investigate the mechanism of action in biological systems.
Member: Cícero Brasileiro M. Neto (Permanent)
Project: Parasite-vector interaction
Description: Effects of secondary metabolites of plants under the control of Aedes aegypti
Member: Dilvani Oliveira Santos (Permanent)
Project: Identification of molecules with the potential pharmacotherapy against biopatogens
Description: Leishmaniose Cutaneous is a neglected disease, whose treatment although effective, has side effects that often cause the interruption of treatment and, consequently, parasite resistance to the drug. Therefore, the objective of this project is based on the search for new drugs that are effective in the treatment of leishmaniasis, but with no toxicity to the host
Member: Helena Carla Castro (Permanent)
Project: Identification of antimicrobial activity and application of computational methods to study the relationship between structure and activity of the toxicological profile of derivatives theory.
Description: The parasitic and bacterial resistance to drugs already present in the pharmaceutical market remains a major concern in the clinic, from which infectious diseases have assumed the condition leading cause of mortality worldwide, and the constant emergence of new resistant strains of microorganisms (and TB) drugs known, remains a major challenge facing medicine to combat them. In this project, are the tests of biological activity in order to identify new active compounds with antibiotic action and / or antiparasitic. Then we use molecular modeling techniques to the study of SAR in order to obtain structural parameters and estereoletrônicos that may be related to the biological activity of synthesized derivatives. The other phase of the project is to calculate the toxicological profile theoretical (in silico) of these derivatives. In this context, it has been tested and evaluated various series of derivatives synthesized in order to identify active compounds.
Member: Luiz Roberto Leão Ferreira (Permanent)
Project: Evaluation of potential modulators on the (Na+-K+) -ATPase activity.
Description: Evaluation of the potential effects of animal and plant extracts on the (Na+,K+)-ATPase activity of rat brain. Isolation and identification of bioactive substances in the biological extracts. Investigation on the mechanisms involved in the modulation of enzyme activity by such substances.
Member: Marcelo Salabert Gonzalez (Permanent)
Project: Role of azadirachtin and ecdysone on the development dynamics of Trypanosoma cruzi in its vector, Rhodnius prolixus.
Description: In this project, we intend to deepen the knowledge about the control of the neuroendocrine system of insects on the development of T. cruzi in their invertebrate hosts. In this sense techniques will be used to manipulate insect neuroendocrine (such as decapitation, head transplantation, denervation, treatment with azadirachtin and ecdysone therapy) to investigate both the ultrastructural organization of the digestive tract (especially the rectal ampulla and cuticle) of R. prolixus and the impact of changes brought about the total population and the various evolving forms of T cruzi in different anatomical segments of the digestive tract of the vector, thus providing additional information on ultrastructural aspects of the digestive tract of insects which particularly favor the genesis of metacyclic trypomastigotes, form of development of the parasite involved in the transmission of this parasite to human hosts.
Member: Izabel Christina N. P. Paixão (Permanent)
Project: Study of antiviral activity (anti-HSV-1, HIV-1 and anti-EBV), and cytotoxic mechanism of action of natural and synthetic substances.
Description: This project aims to study the effects of natural and synthetic substances on the replication of HSV-1, EBV and HIV in cell cultures of VERO (African green monkey kidney) and (peripheral blood mononuclear cells) PBMC, respectively. The cytotoxic effect of substances is evaluated by morphological and molecular analysis of the host cell. As the drugs used to fight viral infection can cause side effects and, due to the emergence of resistant strains is our purpose to find new molecules with activity anti-HSV-1, HIV-1 and anti-EBV with low cytotoxicity and characterize the mechanism of action of most substances promissoras.É We also aim to study the microbicidal activity substâqncias with potential antiviral activity.
Member: Marcelo Salabert Gonzalez (Permanent)
Project: Effects of plant secondary metabolites on the development of Chagas disease vector
Description: In addition to the primary metabolism, responsible for the production of cellulose, lignin, proteins, nucleotides and other substances that perform vital functions of its main, plants also have the so-called secondary metabolism, producer plethora of substances (secondary metabolites) with little or no importance to their growth, development and reproduction, but crucial to the survival of the producing agency for acting on the interrelationship of organisms and the co-evolutionary interactions, especially with phytophagous insects. From this point on new lines of research emerged, adopting different strategies to control pest entomological, among which stands out the use of plant secondary metabolites as regulators of development in insects. Thus, secondary compounds that mimic or antagonize the major insect hormones (eg ecdysone and juvenile hormone) or that induce a reduction or interruption of power, have been identified in several plant species. Certainly the defensive mechanisms used by plants include insect repellent, feeding deterrent, anti-hormones and hormones that can be immensely useful for protection of agricultural plants and control insect vectors of disease. Some of these insecticides derived from plants and known as 30 and 40 generation, are highly toxic to insects and minimally detrimental to human health. Studies on insect physiology and chemistry of plants revealed defensive strategies of plants against insects that do not involve intrinsic toxicity of secondary compounds produced. These strategies promote a direct interruption of the physiological mechanisms required for the specific insect can successfully carry out its metamorphosis, reproduction, diapause and behavior through an interference with your endocrine system, regulating these and other important vital functions, thus representing a point vulnerable in the life cycle of arthropods. This project is part of the Multidisciplinary Program for the Study of Vegetation Fluminense, common to all teachers of the Department of General Biology, in which the vegetation of the state, specifically the flora of salt marshes and the Carapebus Jurubatiba, is investigated by a multidisciplinary team comprised of botanists, chemists, biologists radio, insect physiologists and geneticists. Samples of about 560 specimens were collected, identified and organized into herbarium. In the current screening tests for the biological activity of crude extracts or purified fractions on the development of R. prolixus and / or T. cruzi, have been able to select some candidate substances of interest for use in studies on insect endocrinology systems, vector-parasite interaction and control populations of insect vectors, avoiding major environmental impacts. For several of the compounds studied the biological activities found are surprisingly high and are the subject of further studies to determine whether these substances may or may not prove useful in controlling the barber. Studies currently underway in our laboratory aim to define the chemical factors present in such extracts and their mechanisms of action on the development and life cycle of R. prolixus and T. cruzi. Likewise, several of the specimens collected are still under preliminary screening studies. Thus, our perspective of continuity of this project is long-term productive with continuous supply of new scientific information relevant to the systems studied.
Member: Maria Denise Feder (Permanent)
Project: Study of the activity of secondary metabolites contained in extracts of plant species on the national development of insect pests
Description: In addition to the primary metabolism, responsible for the production of cellulose, lignin, proteins, nucleotides and other substances that perform vital functions of its main, plants also have the so-called secondary metabolism, producer plethora of substances (secondary metabolites) with little or no importance to their growth, development and reproduction but fundamental to the survival of the producing agency for acting on the interrelationship of organisms and the co-evolutionary interactions, especially with phytophagous insects. From this point on new lines of research emerged, adopting different strategies to control pest entomological, among which stands out the use of plant secondary metabolites as regulators of development in insects .
Member: Salvatore G. De Simone (Permanent)
Project: Biotechnology Peptides and Proteins: Immunological and Antimicrobial Applications
Description: The project aims to use information available in database structures / genomic or published in scientific journals on molecules with biological activity found in various bodies of the biodiversity in order to develop drugs with antimicrobial activity and / or diagnostic kits. It's just about the mechanism (natural immunity) used by microorganisms to guard against external aggressors and thus survive, is that efforts to seek nuclear extract information for the development of products for the treatment of human diseases. One of the peptide antibiotics studied, pleurocidina, is found in fish, the second (temporizina, modified peptide) and amphibian comes from the last two toxin mirocina CCDB and B17 are produced by bacteria. With the technology of production of peptides is possible to change them, as well as from the genomes available, find the immunogenic peptide sequences for the development of rapid diagnostic kits .
Member: Saulo Cabral Bourguignon (Permanent)
Project: Evaluation of biological activity of synthetic and natural substances extracted from plants and poisons.
Description: The diseases caused by trypanosomatids, such as Chagas disease and leishmaniasis are endemic and a serious public health problem in several countries at risk of infection, mainly by their insect vectors. Currently, the only therapeutic agent available for Chagas disease in Latin America is benzanidazol. In this context, an intensive research program was focused on the search for alternative drugs, natural and synthetic. The biological activities of derivatives of naphthoquinones such as the B-lapachone, and other compounds such as thienopyridines, acilhidrazonas triazol has been intensively studied. The diversity of antimicrobial, easy access to natural sources of quinones in Brazilian rain forest and the synthetic alternative routes led us to consider lapachol, its derivatives as a starting point for studies of chemotherapy of trypanosomiasis. Substances extracted from snake venoms have also been used as a source of bioactive substances with coagulation activity, anti-coagulant, fibrinogenolítica, vasotensora microbicide and, therefore, with different applications. Thus, this line of research aims to study the effect tripanomicida of natural substances, synthetic and semisynthetic on different evolutionary forms, found in vertebrate and invertebrate hosts of T. cruzi and Leishmania, as well as the identification of other biological activities of these compounds.
Member: Thereza F. Quirico-Santos (Permanent)
Project: Study of biological markers of neuroinflammation and molecular changes associated with clinical progression of gliomas and with the effect of the monoterpene perillyl alcohol.
Description: Study of the genotoxic effect of the monoterpene perillyl alcohol in the central nervous system cells and upon mediators of neuroinflammation, in the tumor microenvironment (stroma), proliferation, migration and angiogenesis of tumor cells. Study the effect of epigenetic changes in the pattern of neuroinflammation and clinical prognosis of the gliomas. In vivo, ex vivo and in vitro studies analyzing the effect of the monoterpene perillyl alcohol in the biological characteristic of glioma cells and / or central nervous system metastases.
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Member: Valéria Laneuville Teixeira (Permanent)
Project: Applied phycology: the use of seaweed natural products as antiviral and snake venom .
Description: This project intends to continue the studies with natural products of marine benthic algae in the field of taxonomy, biogeography and Chemical Evolution. Knowledge of specific chemical algae is undoubtedly the first and primary step to knowledge about the potential of marine algae products on the Brazilian coast. However, we will give priority to studies on the biological activity of natural products of brown algae, because we understand the importance in the development of national drug in the fight against viral diseases and neglected as poisoning by snakes. Poisonous animals are grouped into different families, including vertebrates and invertebrates. The snake venoms are composed of a mixture of substances responsible for various biological effects observed in victims, such as neurotoxicity, effects on platelets, inflammation, cardiotoxicity, myotoxicity, hemorrhage, anticoagulant, hemolytic, hypotensive. In Brazil and elsewhere in the world, the snake bites are a serious problem in society. Currently, the method used is the administration of serum obtained by immunization in horses, which usually reverses the systemic effects, but not always the local effects. This creates a health and economic problem, it can lead to a destruction of tissue resulting in the amputation of a limb. Thus alternative treatments are suggested. And in this sense we seek to evaluate the neutralizing capacity of diterpenes isolated from marine brown algae from the coast of Rio de Janeiro. In the literature we have studies showing biological effects of these structures in different models, such as antibiotic, antifungal, antiviral, antiprotozoal, among others. Our results showed that diterpenes isolated Canistrocarpus pfaff Dictyota cervicornis and were able to neutralize the main biological activities of the venom of Lachesis muta effectively. Therefore, this project aims to carry out a screening of these compounds isolated from several genera of marine algae and test the ability of enzymes to neutralize the poison of the snakes Lachesis muta and Bothrops jararaca, because snakes are important in statistics and severities in accidents snake in Brazil. Seeking to substances in nature with great therapeutic potential. In addition, we will continue the search for new drugs from marine algae with potential antiviral against HSV-1 (herpes simplex type 1), Dengue 2 and HIV-1, a line of research started in 1995.
Member: Verônica Figueiredo do Amaral (Permanent)
Project: Study of the therapeutic, toxic and immunomodulatory heterocyclic derivatives with activity Leishmania
Description: The leishmaniases are zoonoses with the clinical forms of visceral and cutaneous registered in Brazil are considered reemerging. In the state of Rio de Janeiro species L. braziliensis, L. chagasi and L. amazonensis are involved in infection. Despite the epidemiological importance, Leishmaniasis is a neglected disease by the pharmaceutical industry, there are few drugs for the treatment and used in therapy have several adverse effects. Heterocyclic compounds have diverse pharmacological properties including antiviral activity, antitumor, antifungal and anti-inflammatory. Recently we showed that the heterocyclic compound pyrazole carboidrazidas not show toxicity on mouse peritoneal macrophages and are efficient in vitro activity in promastigotes of L. amazonensis and less effective in L. braziliensis and L. chagasi (Samuel Pessoa Prize, 2005. Brazilian Congress of Parasitology). Preliminary data have shown that these compounds reduce the cutaneous lesion and parasite load of mice infected with L. amazonensis. Our working hypothesis is that this compound proved beyond leishmanicidal activity also has important immunomodulatory effect on the host. This project aims to evaluate the therapeutic effect of the immunomodulator and oral administration of carboidrazidas pyrazole in mice infected with L. amazonensis. Consideration will be given the thickness and histopathology of cutaneous lesions, parasite load,
mechanism of action of chemical compounds and their effects on the immune system and in vivo toxicity. This study have important information about a possible use of oral chemotherapy, are likely to use conditional on further studies will enable the improvement of quality of life of the infected population.
Member: Patrícia Burth (Colaborator)
Project: Assessment of the Effects of natural products, synthetic and semi-synthetic activity of the enzyme Na+, K+ atpase.
Description: Besides involvement in regulating ion, evidence indicates the function of Na +, K + ATPase as a hormonal signal transducer. Because of their involvement in numerous cellular functions, there is no doubt that the change of expression and / or enzyme activity may be related to the pathogenesis of many diseases by making this enzyme a powerful therapeutic target. In this project we will evaluate the effect of natural products, synthetic and semi-synthetic, on the activity of the enzyme Na +, K + ATPase in tumor cells of different lineages. Determination whether, similar to cardiac glycosides, these substances also act on several signaling cascades that are modulated via Na +, K + ATPase, which control proliferation and / or cell death. The purpose of this work is to create a system of evaluation of biological activity of substances that allow us to assess the ability induce apoptosis via inhibition of Na +, K + ATPase, using the dosage enzyme in cultured cells, testing, evaluation of apoptosis and cell viability , and studies of the effect of such substances on the cellular signaling cascade via RAS protein.