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).

Our current research focuses on the neurobiology of sleep and sleep-related breathing in the animal models "in vivo" of healthy aging and neuropathology of the most common neurodegenerative diseases of elderly (Alzheimer's Disease (AD), Parkinson's Disease (PD), different types of dementia), aimed to give a new insight into understanding of normal and abnormal sleep, the mechanisms of sleep related behavioural disorders, particularly sleep apnea syndrome, and to identify the neural networks responsible for modifying the regulation of sleep and breathing pattern in different sleep/wake states.

Brain plasticity enables the brain to cope with the environment and is highly volatile in development but highly compromised during aging. The aim of our research is to understand the plastic potential of the brain in different stages of life when exposed to the external challenges. We use the application of general anesthesia (Propofol) in early development and the implementation of various dietary regimes in normal and pathological aging to understand molecular mechanisms underlying plasticity-related processes.

The research focus of this project is to highlight some cellular and molecular mechanisms which underlie neuroinflammation, to identify potential target molecules and signaling pathways. Our aim is to find adequate therapeutic approaches for sanitation of neuroinflammation and promotion of regeneration after the central nervous system (CNS) damage. The efficacy of several therapeutic approaches (purine nucleoside analogues: Ribavirin and Tiazofurin, hyperbaric oxygenation, B vitamins - B1, B2, B3, B6, B12) in suppression of detrimental and enhancement of beneficial inflammatory mechanisms is tested. Considering the pivotal role of extracellular purine nucleotides and nucleosides in the control of neurodegenerative processes and inflammatory responses a particular focus will be put on regulation of their metabolism and the role of ectonucleotidases.

Our research is focused on studying lung, breast, thyroid and brain tumors. Experimental studies include the identification of changes in genes structure, expression, and corresponding proteins function, which could be used as molecular markers for the prediction of tumor progression, response to therapy and disease outcome. By comprehensive analysis of PI3K/Akt/mTOR key molecules in the postoperative material of different tumor types and by comparative analysis of the complete genome originating from tumor and normal tissue using DNA profiling method, we managed to identify changes in DNA related to carcinogenesis and to define new candidate genes responsible for the cancer progression and resistance to therapy.

In yellow-necked mouse, Apodemus flavicollis, B chromosomes are present in almost all populations in a wide range of frequencies that are often stable from year to year, but contribution of Bs to genetic and phenetic structure and their maintenance in the absence of accumulation mechanism, are poorly explored in general. Therefore, we intend to analyse population structure across ecologically different habitats and those situated at the altitude edges of species distribution. Genetic profile of populations will be obtained using molecular markers while phenetic structure will be attained from skull shape analyses, as well as from life-history traits.

Adaptive variation will be investigated by measuring variation at highly polymorphic molecular markers. In the context of genetic structure and presence of Bs, prevalence and intensity of macro parasites dominant for this species, as well as virus's presence, will be monitored. We suppose that obtained data, together with data from analysis of Bs transmission from cages, will allow understanding the contribution of B chromosome polymorphism to genetic diversity and adaptability of species across different environments. Further understanding of mechanism of Bs maintenance in populations is also expected.

This project comprises a group of research tasks centered around the common use of in vitro culture techniques. They include:

Morphogenesis in vitro: Research on shoot regeneration and multiplication, rhyzogenesis, somatic embriogenesis and androgenesis are done on Allium schoenoprassum, Frittilaria meleagris, Iris reichenbachii, Arabidopsis thaliana, Pinus peuce, Pinus heldreichii and wheat, birds-foot trefoil and cabbage subspecies. Protocols designed for specific organogenesis pathways are elaborated and confirmed with cytological and histological studies. Effect of GA3 are studied in regeneration of spinach and bird-foot trefoil. Interaction of GA3 with other hormones is studied by use of light and scanning electron microscopy an in situ hybridization. Following the expression of genes for GA20 oxidase, KNOX/STM and LAS orthologues. Senescence and apoptosis are studied on tobacco leaves.

The Balkan Region represents one of the European major centers of plant diversity, with a substantial number of endemic genera and species. There is an urgent requirement to clarify and improve the methodologies and investigations that enable scientists to conserve, manage and utilize plants and their habitats in this region. We developed ex situ conservation strategies for selected rare and/or endangered plant species, to complement existing long-term in situ conservation efforts. The assessment of genetic diversity in extant populations, as well as establishment and maintenance of seed and/or in vitro germplasm collections which are adopted to fulfill an adequate genetic representation of the genetic makeup of species, is performed.

Contemporary methods of plant biotechnology have a wide application in the commercial production of ornamental plants worldwide. The culture in vitro, findings about physiological roles of phytohormones and molecular cloning techniques are the main elements of plant biotechnology which is focused on the improvement of agricultural production. This project refers to development and application of modern biotechnological methods in the production of ornamental plants. Along with classical research related to study of morphogenesis in vitro, the transformation with Agrobacterium vectors will be conducted in view of producing plants with improved characteristics, while special attention will be paid to development and application of cryobiological methods. Nutritive and hormonal factors of morphogenesis in vitro will be studied for the purpose of the efficient regeneration. These researches would standardize the protocols for micropropagation in Chrysanthemum, Impatiens, Iris and Viola, as well as somatic embryogenesis in the cultures Allium and Iris. The emergence of various viral diseases is a major problem in the conventional production of ornamental plants. For this reason, special attention in this project will be paid to the application of modern cryobiological methods and genetic transformations with aim of producing healthy planting material. Since viral infections increase respiration, causing oxidative stress, the project will focus on the clarification of the mechanism of induced resistance of plants to this type of biotic stress. The development of the methods for regeneration, genetic transformation, cryopreservation, as well as studying stress and other physiological processes will contribute to the improvement of protocols for obtaining healthy planting material of ornamental plants.

Heat stress (HS) represents one of the most important limiting factors to crop productivity worldwide. As a result of global warming, potato yield losses of 10-26% are predicted for region of Southeast Europe, including Serbia, in the next 30 years. These losses can be reduced on 5-11% with adaptation in production methods concerning use of heat tolerant cultivars. The scope of proposed project comprises development and application of protein markers for fast and efficient heat tolerance screening of potato cultivars. Our project proposes utilization of stress proteins related to HS-tolerance and heat-labile proteins as a protein markers. Results of protein marker quantitative analysis will be correlated with morphometric parameters and yield parameters under HS for each of examined genotypes using adequate statistical methods and an optimal combination of protein markets will be selected. Our expectations are that proposed project will result in biotechnological solution for protein marker assisted screening for heat tolerance in potato and identification of HS tolerant potato cultivars suitable for growing in Serbia under changed climate conditions.

The specific area of research represents investigation of regulation of oxidant-induced changes of aerobic organisms and we develop three various areas of investigation: 1) biomonitoring of aquatic organisms, 2) toxicology and 3) biomarkers and pathophysiological states.

1) Biomonitoring of aquatic organisms. Molecular and physiological biomonitoring based on the antioxidant defense enzyme activities as biochemical biomarkers: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and the concentrations of vitamin E, vitamin C, glutathione.

2) Toxicology. Prooxidative effects of cadmium and cisplatin in acute and chronic treatment and protective role of antioxidants on alteration of oxidative stress biochemical biomarkers in the blood and tissues of mail Wistar albino rats will be investigated.

3) Biomarkers and pathophysiological states. The study of estradiol and its role inpreeclampsia, the assessment of oxidative damage and antioxidative capacity of healthy tissues in response to therapeutic doses of radiation in the treatment of breast cancer and the pathogenesis of gastrointestinal disorders will be investigated.

The aim of the project is to assess the influence of heterogenity of abiotic and biotic environment at molecular, citological and morphological on variability, as well as variability of life history traits and behaviour, population structure and evolution processes (genetic specialisation, phenotype plasticity, speciation) of different organisms (vertebrates, invertebrates and plants). Achieved results will enable assessment of appropriate indicators of environmental devastation and will be included in phylogeographic analyses and ecological status evaluation of the ecosystems in region and Europe.

The amphibians and reptiles of the Balkan Peninsula included in the scope of the proposed research represent a "natural laboratory" and excellent model-system for both evolutionary and conservation studies. These vertebrates are characterised by low dispersal abilities and mostly strict ecological requirements, resulting in high evolutionary differentiation and intraspecific variation in their morphology, genetics, life history and ecology. The specificity of the Balkans with its complex paleogeographic history, heterogeneous landscapes, topographic diversity and climatic variation, resulted in a complex picture of amphibian and reptile diversity. Moreover, the Balkans are the origin of numerous taxa, an area of high endemicity, high rate of allopatric and parapatric speciation, and numerous hybridization zones. By combining data from natural populations and experimental studies, we propose to examine the following issues in evolutionary biology: (1) the evolution of complex morphological entities, (2) the evolution of life-history traits, (3) phylogeographic patterns of evolutionary lineages, and (4) the relation between eco-geographical and environmental variables as a function of the distribution of species, phylogenetic lineages and hybrid zones. Conservation research studies will be related to the recognition of evolutionary significant units, and to population ecology studies as a basis for further conservation strategies of autochthonous populations and species.

In modern biology there are two alternative experimental approaches for the study of different phenomena, which impact the evolution of living being – laboratory evolution and investigations in the wild.

LABORATORY EVOLUTION

Laboratory evolution allows the study of populations across multiple generations under strictly defined and reproducible conditions, but without the direct choice of reproducing individuals by the experimenter, in contrast to natural populations, where environmental conditions can be an efficient evolutionary factor that produces adaptations.

By employing "laboratory natural selection" as a tool to investigate determinants of life-history evolution, four types of laboratory populations of the seed beetle, Acanthoscelides obtectus, have been established (each type was replicated four times and observed over 200 generations): populations selected at high (K) and low (r) larval densities (density-dependent selection), and populations in which selection was imposed on either early (E) or late (L) reproduction (age-specific selection). Using these populations, the future investigations will focus on the following topics: 1. The evolutionary outcomes of density-dependent and age–specific selection, 2. The quantitative-genetic basis of the life-history traits that respond to these two selection types, 3. The evolution of ageing and late life, 4. The evolution of pre-zygotic and post-zygotic reproductive isolation between populations within each selection regime.

The aim of the project is investigation of the effects of environmental agents on important physiological homeostatic system, immune system, of mouse-like rodents. Cellular and molecular mechanisms of immunomodulatory potential of two environmental xenobiotics (ubiquitous pollutant cadmium and anticoagulant warfarin, used for control of pest rodents) is investigated in laboratory populations of Norway rat ( Rattus norvegicus). The effect of these agents on immune system is analyzed using parameters of basal immune activity and in settings of immune response induction as well. Distinct aspect is examination of the impact of these agents on laboratory rat's resistance to opportunistic fungus Aspergillus fumigatus. Wild Norway rats harbor variety of parasites and microorganisms and are thus considered as natural biological models suitable for examination of immune function in settings of multiple infections. Analysis of basic parameters of immune function as well as immune-mediated damage of peripheral tissues of Norway rats from urban environment and comparison with same parameters in several laboratory strains of Norway rats gives insight into the effect of the environment on immunity.

The Balkan Peninsula, where Serbia is situated, is a dendroflora diversity centre (IUCN), home to forests comprised of relict, endemic, economically important (or potentially important) and endangered forest species, unique in time and space. Serbia's gorges, canyon valleys and mountain massifs represent particularly rich reservoirs and treasure troves of the genofund. It is these refugia that have enabled the preservation and reproduction of the rich and varied flora, particularly tertiary relicts and endemorelicts, and represent veritable museums in vivo of special scientific importance. The diversity of small local populations is also of particular importance, as is the diversity of those on the edges of forest belts, the most sensitive parts of the ecosystem. The project presumes that the autochthonous forest flora and vegetation of our part of the Balkan Peninsula contain populations whose presence, specific genetic structure, chemical composition, morphophysiological and reproductive characteristics reveal the history of the vegetation and contribute to a better understanding of the plants' adaptive potential to survive in adverse environmental conditions.

In anthropogenically degraded habitats, plants are often limited by multiple stress factors that act simultaneously, threatening the functioning of plants and exhausting their adaptive potential.

Our research is based on studying plants' physiological, biochemical and morphological responses to the effects of multiple stressors. These determine their adaptive capacity to survive and/or develop tolerance to stress in such habitats. Research will be undertaken at two types of such habitats: ash deposits at the 'Nikola Tesla-A' thermal power plant in Obrenovac (initially biologically empty areas with high pollutant levels) and urban zones in Belgrade (highly polluted degraded areas). In aiming to establish plants' ecophysiological adaptive strategies for surviving in multiple stress conditions in degraded habitats, research will focus on defining the ecological factors that limit plant survival and functioning in degraded habitats, establishing the synergetic, antagonistic or additive effects of multiple stressors, identifying structural and functional plant damage, and defining plants' adaptive response to the effects of multiple stress and their adaptive potential to survive in such conditions. Identification of the adaptive strategies of plants that colonise, survive and function at thermal power plant ash deposits and in urban zones subject to chronic pollution can be a guide for creating activities aimed at the ecological restoration of disturbed ecosystems.