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.

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.

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.