National project

Biomarkers in neurodegenerative and malignant processes (BNMP)

Project ID : III41005
Period : 2010-2016
Principal investigator : Prof. Pavle R. Andjus, PhD
Description : The main goal is finding a reliable in vivo biomarker for diagnosis, prognosis and follow-up of the therapeutic response in neurodegeneration and cancer. This translational research includes 7 institutions (academia, institutes, clinics) and experts of different profiles (biologists, physical chemists, doctors) as well as young researchers and international partners. It consists of 3 inter-related sub-projects:

1. experimental markers – basic study of molecular and cellular indicators of pathogenesis mechanisms,
2. preclinical markers – MRI and EPR study of endogenous (free radicals and metals) and exogenous (contrasting cellular nano-probes) markers in animal models, and
3. clinical markers – MRI study of selected biomarkers in patients supported by ex vivo EPR.

In vitro and in vivo studies translate towards the diagnostics of ALS, Alzheimer’s disease, ischemia, neural tumors and breast cancer. Basic research deals with the mechanisms of inflammation and ischemia, ions and free radicals as markers in pathogenesis, metabolic status and organization of cellular organelles and correlation of neuropathology and malignancy. The preclinical phase aims to contribute to the understanding of markers of oxidative status and the role of free radicals, particularly the degree of infiltration of macrophages/microglia and lymphocytes and the integrity of the blood-brain barrier. Clinical sub-project aims to determine the target MRI markers and develop optimal acquisition protocols.

CLM has an intense and long lasting collaboration with the group of prof. Goran Bačić from the neighboring Faculty of Physical Chemistry, University of Belgrade. Teaming with this group was performed in the field of preclinical magnetic resonance studies – MRI and EPR. This collaboration was crowned by the acquisition of a state-of-the-art EPR imager (Bruker Elexsys II Dual Band) and the formation of the EPR lab at the Faculty of Physical Chemistry, all through a national grant (III41005) run by the head of CLM, prof. P.R. Andjus.

International projects

Bilateral projects

Study of stem cells for experimental therapy of amyotrophic lateral sclerosis

Period : 2016-2017
Participants : The University of Zagreb, Croatia || CLM, Faculty of Biology, University of Belgrade, Serbia

Towards molecular and genomic markers in amyotrophic lateral sclerosis

Period : 2014-2016
Description : Key factors initiating ALS are mostly unknown. Despite of numerous trials, effective therapy in ALS remains elusive. In the absence of adequate biomarkers, the crucial events leading to pathological cellular processes are ignored. Addressing the sequence of events related to the degeneration of the affected motor neurons in the rat bearing human SOD1 gene with G93A mutation (a widely used ALS model) on whole animals (MRI) and cell cultures – at synapses and cell bodies (patch clamp and Ca2+ imaging), may help to identify primary targets of the disease. A similar study of unaffected motor neurons may help to reveal factors responsible for the resistance. Recent evidences also indicated that the regulation of RNA metabolism in the skeletal muscle at the site of neuromuscular junction (NMJ) is an emerging mechanism involved in ALS pathogenesis. microRNAs (miRNAs) could be the key mediator of this process but no clear explanation of the basic molecular events occurring in ALS muscles have been proposed. The unraveling of molecular networking which could underlie the retrograde signaling at the NMJ would be of interest to this goal. More in general, accumulating evidence indicates that misregulated miRNAs can contribute to neurodegenerative diseases and at the same time may serve as biomarkers. miRNAs will be screened in the rodent ALS model (blood and muscle, neural tissue)in order to detect alterations in the expression of miRNAs (miRNA fingerprinting) in the early disease stage as well as in disease progression. miRNAs will also be screened in blood and muscle from ALS patients and age-matched controls selected at the Gemelli Hospital will be compared to the findings on SOD1G93A rat model. GENECHRoN Srl (Rome) will manage possible translational exploitations .
Participants : Universita Cattolica del Sacro Cuore, Rome, Italy || CLM, Faculty of Biology, University of Belgrade, Serbia

Involvement of tenascin-C in astrocyte scarring after spinal cord injury

Period : 2015-2016
Description : We aim to investigate the function of tenascin-C (TNC) in glial scar formation by the use of the recombinant fragments (alternatively spliced domains) of the TNC molecule in the well-established model of mouse spinal cord injury. TNC was chosen because its impact on the locomotor recovery after spinal cord injury is known, but due to its complex structure with multiple domains, its full therapeutic potential has not been explored so far.

• aim 1 : To investigate impact of TNC and its fragments on astrocyte motility and reactive gliosis astrocyte scratch assay as an in vitro model will be used.
• aim 2 : To investigate the influence of TNC fragments on glial scar formation in vivo after spinal cord injury lower thoracic spinal cord compression will be performed in wild-type and TNC-deficient (TNC-/-) mice.

Participants : DAAD; Center for Molecular Neurobiology, Hamburg, Germany || CLM, Faculty of Biology, University of Belgrade, Serbia

 

Multilateral projects (actions)

EU-ROS

Period : 2012-2016
Type : COST Action BM1203 – international collaboration
Description : Life requires oxygen. This runs the risk that, when oxygen leaks out from normal metabolism, reactive oxygen species (ROS) are formed, which – when too high – trigger disease. With the idea to overcome this, antioxidants are heavily marketed, yet without proof of their effectiveness. Rather, worrying evidence suggests adverse effects. This paradox is due to the fact that ROS are not only ‘bad’, but – in tightly regulated amounts – also act as essential signalling molecules. Unravelling the fine balance between ROS acting as a friend or a foe is fundamental to understand aerobic life. To advance this important area of biology and medicine, highly synergistic approaches combining diverse and scattered disciplines are needed. For this, COST provides an ideal framework. EU-ROS will bring together multi-disciplinary experts to enhance the competitiveness of European research. By applying fundamentally new approaches it will generate advanced knowledge and translate this into novel applications ranging from medicine to crop science. With its dynamic structure, EU-ROS will attract further experts and particularly support capacity building of the future European research leaders and talented women. Collectively, EU-ROS will overcome the fragmentation of European R&D on oxygen/ROS research while its translational components will contribute to European societies’ economic growth and wellbeing.
Link : COST Action BM1203

Inter-institutional collaboration

Cellular and molecular basis of neuroinflammation: potential targets for translational medicine and therapy

Project ID : III41014
Project headquarters : Institute for Biological Research „Siniša Stanković”, Department of Neurobiology
Principal investigator : Prof. Nadežda Nedeljković, PhD
Sub-project : The role of purinergic signalling in acute and chronic neuroinflammation
Period : 2010-2016
Type : Integral interdisciplinary studies
Description : 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. 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. Besides in vivo neuroinflammatory processes are also studied in vitro in primary astrocytic and microglial cell culture, and glial cell lines. Read more…
Participant : Marija Adžić, PhD candidate