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Diabetes mellitus is a complex metabolic disorder that can be presented in two major forms, as type 1 diabetes (T1D) and the much more common type 2 diabetes (T2D). While their etiologies are different, both diabetes types are characterized by hyperglycemia resulting either from insufficient insulin levels in T1D, or an insensitivity of target cells to insulin in T2D. In T1D, the death of insulin-producing pancreatic β-cells in an autoimmune response is a comparatively rapid event, whereas in T2D loss of β-cell mass occurs over years as interactions of extrinsic stressors and intrinsic factors continually impair β-cell functioning. The decline in the total mass of functional β-cells required to provide insulin for maintaining glucose homeostasis underlies diabetes development. Insight into the molecular control mechanisms in β-cells and the pathology of diabetes has laid the foundation for the paradigm for diabetes treatment based on the application of strategies that support functional β-cells by suppressing cytotoxic cell signaling and preventing the activation of cell death pathways. Our research is focused on β-cells as the principal element in diabetes development, and on hepatocytes and cardiomyocytes as the targets of diabetic complications. Our experimental systems include the in vivo model of streptozotocin (STZ)-induced diabetes in the rat, and in vitro models employing different cell lines maintained in culture.

Modulation of immune response and cell death represents a key strategy in the therapy of cancer and inflammatory disorders such as multiple sclerosis, and diabetes. However, targeting inflammation for therapeutic reasons is very complex, due to numerous underlying damaging pathways. The main goal is therefore to gain insight into control molecular mechanisms of these disorders and, thus, contribute to the design of therapeutics for prevention and treatment of the diseases. It is proposed to investigate the role and mode of action of biologically active microenvironment molecules (cytokines, ROS, NOS, hormones) and genetic factors in regulation of proliferation, differentiation, function, and cell death of immune and target tissue cells, in both physiological and pathological conditions. To establish basic control mechanisms of inflammation, immune response to (auto)antigens and resistance to anti-tumor immune response, the role of relevant intercellular mediators and intracellular signaling pathways, our research will be performed by in vivo and in vitro approaches using animal models of human diseases in inbred and/or genetically modified murine strains, and primary or transformed cell populations of various origins. In addition, cytotoxic, cytoprotective and immunomodulatory potential of various pharmacological agents or natural plant and animal products will be investigated, as well as intra- and intercellular mechanisms underlying the observed biological effects.

Multiple sclerosis is inflammatory, autoimmune disease of the central nervous system (CNS). The immune response directed towards cells and structures of CNS tissue causes demyelinization and neurodegeneration, thus inducing various neurological deficits in patients. In majority of patients multiple sclerosis takes relapsing-remitting or chronic progressive course. Experimental autoimmune encephalomyelitis (EAE) induced in DA rats is a model of multiple sclerosis and shares numerous immunopathogenic features with the human disease. Still, there is a major difference in the clinical course, as EAE in DA rats is acute monophasic disease. DA rats completely recover from EAE and are highly resistant to further attempts of the disease induction. The main goal of this project is to identify cell populations and molecular mechanisms responsible for the recovery of DA rats from EAE and their resistance to EAE re-induction. Consequently, the obtained knowledge should be useful for improvement of multiple sclerosis therapy.

The aim of our research is to examine the effects of selected plant extracts, phytoestrogens (genistein, daidzein), steroid (estradiol, progesterone, testosterone, dexamethasone) and peptide hormones (somatostatin, calcitonin, ghrelin) on neuroendocrine and mineral homeostases in rats. Herbal and nature alternatives to hormone replacement therapy are intensively advertised for maintenance of hormone balance, prevention of cardiovascular problems, atherosclerosis and osteoporosis in both sexes. Assessments of effects of these substances on: (i) hypothalamo-pituitary -adrenal, -somatotropic, -thyroid and -gonadal axes; (ii) neuroendocrine C-cells, bones, parathyroid glands and kidneys; and (iii) cellular mechanics are important for evaluation of their health risks / benefits and potential use in treatment of cancer, cardiovascular and other diseases. The examinations are carried out in rats of different age (adult, middle and old age) and sex, with special emphasis on models of andropause and menopause. In vitro studies of cellular mechanics are performed using erythrocytes or prostate cancer cells. Glucocorticoids are used in human pregnancies at risk of preterm delivery because they reduce neonatal mortality and morbidity. However, this treatment enhances maturational processes and provokes permanent changes in physiological systems. Thus, short-term beneficial effects of prenatal glucocorticoids are, at the same time, the ones that increase the long-term risks of dysregulation of the metabolic function and endocrine axes, including stress response, growth and reproduction. Effects of prenatal glucocorticoid overexposure are examined in rats from their fetal period of life till adulthood.

The Laboratory of Professor Matić gathers a group of young scientists committed to the study of neuroendocrine and dietary aspects of the development of Metabolic Syndrome, which is one of the leading health problems worldwide. Our scientific endeavors are primarily focused on the molecular mechanisms of glucocorticoid hormones actions in the development of Metabolic Syndrome, since these hormones are important regulators of energy homeostasis, metabolic inflammation, as well as of insulin and leptin signalling pathways. In the next three years the role of stress and fructose diet in the development of Metabolic Syndrome will be elucidated through collaboration with Professor Luc Tappy's group from Switzerland as a part of the SCOPES Joint Research Project entitled: Interactions between stress and dietary fructose in the development of the metabolic syndrome: role of glucocorticoids.

Program of basic research

"Ekološko-genetičke studije varijabilnosti populacija Drosophila" #1527, Project Leader: Dr. Marko Anđelković

"Indikatori narušenosti strukture i metaboličkih funkcija u terestričnim ekosistemima" #1565, Project Leader: Dr. Branko Karadžić

"Adaptacije u prirodnim i laboratorijskim populacijama" #1570, Project Leader: Dr. Branka Tucić

"Fiziološki, citološki i biohemijski aspekt in vitro regeneracije reliktnih, endemičnih i ugroženig biljnih vrsta" #1573, Project Leader: Dr. Ljiljana Radojević

"Plastičnost rasta i fiziološka plastičnost u odgovoru na sredinski stres kod fitofagnih šumskih insekata" #1615, Project Leader: Dr. Jelica Lazarević

"Integrativna istraživanja vodozemaca i gmizavaca centralnog Balkana" #1623, Project Leader: Dr. Miloš Kalezić

"Limnološka ispitivanja Dunava i Đerdapske akumulacija (1171-943 km)" #1628, Project Leader: Dr. Vesna Martinović-Vitanović

"Efekti magnetnih polja i neuroaktivnih supstanci kao modulatora aktivnosti centralnog nervnog sistema" #1636, Project Leader: Dr. Zlatko Prolić

"Plastičnost mozga: ekspresija neuronalnih gena u fiziološkim i patološkim stanjima" #1641, Project Leader: Dr. Selma Kanazir

"Neurohemijski i neurofiziološki mehanizmi oštećenja i oporavka centralnog nervnog sistema" #1647, Project Leader: Dr. Mirjana Stojiljković

"Modulacija funkcije glukokortikoidnog receptora u toku ćelijskog odgovora na stres" #1654, Project Leader: Dr. Gordana Matić

"Modulacija ekscitabilnosti membrane i ritmovi bioelektrične aktivnosti neurona beskičmenjaka i kičmenjaka. Analiza i modeliranje" #1660, Project Leader: Dr. Milka Ćulić

"Sistemski odgovor na promenjen redoks status" #1669, Project Leader: Dr. Mihajlo Spasić

"Genetički polimorfizam u prirodnim populacijama sisara – poreklo, održavanje i efekti B hromozoma" #1693, Project Leader: Dr. Mladen Vujošević

"Svetlosna i hormonalna kontrola rastenja i razvića biljaka" #1696, Project Leader: Dr. Dragoljub Grubišić

"Karakterizacija potencijalnog psihotrpnog dejstva nekih novosintetisanih i prirodnih neuroaktivnih supstanci" #1704, Project Leader: Dr. Mirko Tomić

"Morfofunkcionalna ispitivanja efekata hormona na neuroendokrini sistem tokom životnog ciklusa" #1710, Project Leader: Dr. Milka Sekulić

"Genetički modifikovane i in vitro gajene biljke – modifikacija morfogeneze, sekundarnog metabolizma i ekonomski značajnih osobina" #1716, Project Leader: Dr. Branka Vinterhalter

"Molekularni mehanizmi regulacije transkripcije gena za akutno-fazne proteine" #1722, Project Leader: Dr. Goran Poznanović

"Evolucija u heterogenim sredinama" #1725, Project Leader: Dr. Jelka Crnobrnja-Isailović

"Ćelijska i molekulska osnova modulacije imunskih poremećaja" #1664, Project Leader: Dr. Stanislava Stošić-Grujičić

"Biodiverzitet i očuvanje genofonda drveća u Srbiji" #1932, Project Leader: Dr. Srđan Bojović

National projects managed by other institutions

„Razvoj visokoproduktivne akvakulture i njene primene u zaštiti i unapređenju ribljih resursa” #1354. Lead Partner: Institute for Multidisciplinary Research, University of Belgrade. Project Leader: Dr. Miroslav Nikčević.

„Diverzitet i fiziologija gljiva i antimikrobna aktivnost sekundarnih metabolita biljaka i gljiva” #1511. Lead Partner: Faculty of Biology, University of Belgrade. Project Leader: Dr. Jelena Vukojević.

„Inventarizacija, monitoring i vrednovanje komponenti faune u integralnoj zaštiti biodiverziteta” #1525. Lead Partner: Faculty of Biology, University of Belgrade. Project Leader: Dr. Ivica Radović.

„Vegetativno i generativno razmnožavanje in vitro ugroženih biljnih vrsta, u cilju ex situ zaštite i produkcije sekundarnih metabolita” #1530. Lead Partner: Faculty of Biology, University of Belgrade. Project Leader: Dr. Radomir Konjević.

„Neuroendokrina kontrola enzimskih sistema i redoks regulacija u uslovima izmenjene homeostaze” #1550. Lead Partner: Faculty of Biology, University of Belgrade. Project Leader: Dr. Vukosava Davidović.

„Hemijske i biohemijske konsekvence metal-ligand interakcija” #1569. Lead Partner: Scientific Institution Institute of Chemistry, Technology and Metallurgy, University of Belgrade. Project Leader: Dr. Svetozar Niketić.

„Steroidogeni i antioksidativni enzimi kao indikatori hemijskih stresora iz okoline” #1766. Lead Partner: Faculty of Sciences, University of Novom Sadu. Project Leader: Dr. Radmila Kovačević.

„Membrane i apoplast. uloga u spoljašnjem i oksidativnom stresu i biohemijskoj regulaciji redoks procesa simplasta” #1934. Lead Partner: Institute for Multidisciplinary Research, University of Belgrade. Project Leader: Dr. Željko Vučinić.

„Gensko testiranje u praksi” #2019. Lead Partner: Vinča Institute of Nuclear Sciences, University of Belgrade. Project Leader: Dr. Bogomir Dimitrijević.

Program of basic research

"Akutni i hronični stres: mehanizmi regulacije homeostaze u akutnoj radiacionoj bolesti i dijabetesu" #143002, Project Leader: Dr. Goran Poznanović

"Ekspresija i funkcija glukokortikosteroidnog receptora i proteina toplotnog stresa u patofiziološkim stanjima i stresu." #143003, Project Leader: Dr. Gordana Matić

"Molekularna i bihevioralna istraživanja plastičnosti nervnog sistema" #143004, Project Leader: Dr. Selma Kanazir

"Interakcija glije i neurona u procesu oporavka nakon oštećenja centralnog nervnog sistema" #143005, Project Leader: Dr. Mirjana Stojiljković

"Uticaj fitoestrogena, steroidnih i peptidnih hormona na ćelije neuroendokrinog sistema" #143007, Project Leader: Dr. Milka Sekulić

"Identifikacija specifičnih gena za terapiju kancera" #143009, Project Leader: Dr. Sabera Ruždijić

"Genetička raznovrsnost u prirodnim populacijama – uloga B hromozoma" #143011, Project Leader: Dr. Mladen Vujošević

"Adaptivni značaj genetičkog polimorfizma populacija Drosophila" #143014, Project Leader: Dr. Marko Anđelković

"Efekti traumatskih, neurotoksičnih i neuroprotektivnih faktora na električnu aktivnost mozga sisara. Analiza i modeliranje" #143021, Project Leader: Dr. Milka Ćulić

"Tekuće vode Srbije - istraživanje biodiverziteta i korišćenje podataka u tipologiji, izradi ekološkog indeksa i monitoringu ekološkog statusa" #143023, Project Leader: Dr. Predrag Cakić

"Ekofiziološke karakteristike biljaka i njihov potencijal u obnavljanju biodiverziteta narušenih ekosistema" #143025, Project Leader: Dr. Pavle Pavlović

"Regulacija morfogenetskih procesa i sekundarnog metabolizma i genetičke transformacije biljaka u kulturi in vitro" #143026, Project Leader: Dr. Branka Vinterhalter

"Uticaj magnetnih polja kao ekofiziološkog faktora na različite biološke sisteme i moguća primena u biomedicini" #143027, Project Leader: Dr. Zlatko Prolić

"Fiziološka i farmakološka modulacija imunoinflamatornih i malignih bolesti" #143029, Project Leader: Dr. Stanislava Stošić Grujičić

"Svetlosna i hormonalna kontrola rastenja i razvića biljaka, razmnožavanje in vitro i ex situ zaštita retkih i ugroženih vrsta" #143031, Project Leader: Dr. Dragoljub Grubišić

"Biomedicinska ispitivanja i razvoj nekih novih psihotropnih supstanci" #143032, Project Leader: Dr. Mirko Tomić

"Fiziološki i evolucioni aspekti stresnog odgovora u prirodnim i laboratorijskim populacijama" #143033, Project Leader: Dr. Jelica Lazarević

"Uloga redoks aktivnih supstanci u procesima održavanja homeostaze živih sistema" #143034, Project Leader: Dr. Duško Blagojević

"Proučavanje poremećaja homeostaze i određivanje biomarkera oksidacionog stresa kod aerobnih organizama" #143035, Project Leader: Dr. Zorica Saičić

"Istraživanja ekotoksikoloških aspekata delovanja ksenobiotika i biotičkih agenasa na populacije mišolikih glodara" #143038, Project Leader: Dr. Dragan Kataranovski

„Evolucija u heterogenim sredinama" #143040, Project Leader: Dr. Aleksej Tarasjev

"Diverzitet vodozemaca i gmizavaca Balkanskog poluostrva" #143052, Project Leader: Dr. Miloš Kalezić

„Hemijska trauma mozga: biohemiske i kliničke posledice" #143057B, Project Leader: Dr. Ankica Jelenković

Program of research in the field of technology

"Unapređenje proizvodnje ukrasnih biljaka primenom novih tehnologija" # TR6833B, Project Leader: Dr. Angelina Subotić.

National projects managed by other institutions

„Biofizička istraživanja membranskih procesa. interakcija membranskih receptora i kanala sa spoljašnjim faktorima i intracelularna regulacija” # 143016. Lead Partner: Institute for Multidisciplinary Research, University of Belgrade. Project Leader: Dr. Željko Vučinić.

„Taksonomska, biohemijska i molekularna istraživanja gljiva i biološki aktivnih supstanci” #143041. Lead Partner: Faculty of Biology, University of Belgrade. Project Leader: Dr. Jelena Vukojević.

„Istraživanja diverziteta, zaštite i održivog korišćenja faune riba, kao bitnih komponenti za razvoj strategije integralnog upravljanja vodenim resursima Srbije” # 143045. Lead Partner: Institute for Multidisciplinary Research, University of Belgrade. Project Leader: Dr. Mirjana Lenhardt.

„Strukturne, hemijske i molekularne karakteristike nekih biljnih vrsta-fundamentalni značaj i primenljivost” # 143049. Lead Partner: Faculty of Biology, University of Belgrade. Project Leader: Dr. Petar Marin.

„Fiziološki, morfološki i molekulski mehanizmi termoregulacije u adaptivnim procesima izmenjene homeostaze” # 143050. Lead Partner: Faculty of Biology, University of Belgrade. Project Leader: Dr. Gordana Cvijić.

„Biofizičko neuroprofiliranje na eksperimentalnim modelima oštećenja i oporavka centralnog nervnog sistema” # 143054. Lead Partner: Faculty of Biology, University of Belgrade. Project Leader: Dr. Pavle Anđus.

„Citotoksični, citoprotektivni i imunomodulatorni efekti nanočestica” #145073. Lead Partner: School of Medicine, University of Belgrade. Project Leader: Dr. Vladimir Trajković.

„Geološka i ekotoksikološka istraživanja u identifikaciji geopatogenih zona toksičnih elemenata i prirodne radioaktivnosti u akumulacijama vode za piće u Republici Srbiji” #146021. Lead Partner: Scientific Institution Institute of Chemistry, Technology and Metallurgy, University of Belgrade. Project Leader: Dr. Milka Vidović.

„Interakcije prirodnih proizvoda i njihovih analoga sa proteinima i nukleinskim kiselinama” #142026. Lead Partner: Faculty of Chemistry, University of Belgrade. Project Leader: Dr. Dušan Sladić.

„Regulatorni peptidi u integrativnim procesima nervnog i endokrinog sistema” #145003. Lead Partner: School of Medicine, University of Belgrade. Project Leader: Dr. Vesna Starčević.

Industrial and technological progress increases the incidence of magnetic fields of different characteristics in our working and living environment. The subproject "Neurophysiological and behavioral responses of different species to external magnetic fields" (led by Dr. Branka Petković) deals with the effects of magnetic fields, particularly on the neuroendocrine system, in insects (Drosophila sp., Musca domestica, Tenebrio molitor, Baculum extradentatum, Morimus funereus,...), snail (Helix pomatia) and mammals (Rattus sp., Meriones unguiculatus). Electrophysiological studies in vitro and in vivo, histological and biochemical analyses (oxidative stress parameters, nucleotide content, gases turnover, enzyme and receptor activities), monitoring of development and behavior in selected model systems are planned. Obtained results reveal the mechanisms of magnetoreception in evolutionary distant species and whether magnetic field-induced response is unique or species-specific.

Macroautophagy (hereafter reffered to as autophagy) is a process of intracellular protein digestion in autophagolysosomes, allowing for removal of damaged proteins and preservation of energy and survival during metabolic stress, but also able to cause cell death when activated innapropriately. The main aim of the project is to establish the role of autophagy in therapy-induced death of cancer cells. The induction of autophagy and underlying molecular mechanisms will be investigated in cancer cell lines treated with various conventional (e.g. cisplatin, taxol, cytarabine, idarubicin) or experimental anticancer agents (e.g. metformin, statins, indomethacin, nanoparticles).

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