NATIONAL RESEARCH PROJECTS

The table indicates the national projects or programmes in which BTC has the leading or participating role and which are financed by the Slovenian Research Agency (ARRS).

BTC as the leading research organisation

Programme P3-0371: Human stem cells - advanced cell treatment. Advanced cell treatment has been one of the basic focuses in biomedical research and development for the past decade. The application of new post-genomic technologies and systems biology provides new answers to certain fundamental scientific questions. Today, the central questions also concern embryonic stem cells that hold the best therapeutic properties due to their pluripotent character; however their application is a matter of dispute due to ethical reservations. For this reason, it is vital to use alternative approaches that use cell lines similar to embryonic cells, which can be obtained from other postnatal tissues, such as the umbilical cord, bone marrow or peripheral blood of adults. The findings obtained from lot 1 (preclinical procedures) and the development of successful in vitro procedures of stem cell differentiation and maturation into the cells of three germ layers of endoderm, ectoderm and mesoderm are expected to shed new light on the development of stem cells in an adult that could be used instead of embryonic stem cells, which would be a major leap in the development of advance cell treatment.
The findings obtained from lot 2 (clinical research) will provide a basis for an extended clinical application of various types of stem cells and other cells. It is expected that a positive outcome of these studies will lead to extended indications for advanced cell treatment, spreading to degenerative diseases of the nervous system, treatment of nerve damage, diabetes and cardiovascular diseases. Collaboration with the University Medical Centre in Ljubljana and Educell Ltd..

Project Z1-4302: Development and optimization of the clinical potential of tolerogenic dendritic cells and the immunomodulatory role of the DC-SIGN lectin receptor. Dendritic cells cover a heterogeneous population of the most important antigen-presenting cells that play the central role in the control of immune processes taking place between the innate and adaptive immune system. Dendritic cells stand out for the extraordinary efficiency of active antigen presentation, as they are distinguished for their distinct functional plasticity, due to which dendritic cells can initiate both activation as well as regulatory immune processes. Under certain conditions, dendritic cells can obtain tolerogenic properties. DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) is a lectin receptor that is selectively expressed by dendritic cells. It affects the recognition of antigens, cell adhesion and modulation of dendritic cell activity. DC-SIGN recognises several viral (Ebola, HIV-1, etc.) and non-viral pathogens (M. tuberculosis, H. pylori, etc.). Many pathogens use the binding to DC-SIGN to speed up their infectivity and avoid the classical processes of antigen-presentation and dendritic cell activation, allowing them to survive in the host. Due to the recently discovered immunologic role of DC-SIGN, a lot of questions regarding its influence on the development and function of dendritic cells still remain open. The mentioned receptor has also become an important therapeutic target in the search for new antimicrobial agents. The work performed within the scope of this project will include research of the still undiscovered aspects of the immunomodulatory role of DC-SIGN, a detailed understanding of the signalisation related to DC-SIGN and the identification of agonism/antagonism of new DC-SIGN synthesis inhibitors. Post-doctoral project.

BTC as the participating research organisation
Research programme

Programme P3-0343: Aetiology, early detection and treatment. Knowledge and understanding of the genetic background of chronic diseases has enabled the planning of individualised long-term clinical patient treatments and, at the same time, been the basis for genetic consultation. Knowledge of the morphological background of a disease can provide a starting point for efficient treatment. The research programme focuses on autoimmune diseases and their combinations that feature different clinical pictures, but are related through genetically conditioned aetiology. The focus of the research is on the genetic and immunological background of complications that are related to the most common incurable chronic endocrine or metabolic disorder and one of the most common incurable chronic diseases ever, i.e. type 1 diabetes. It is expected that the research conducted will contribute to the fundamental knowledge of individual areas that are related in this interdisciplinary-based project. At the same time, it is desired that research results have a direct impact on diagnostic algorithms and the clinical course of the treatment of an individual pathological state. Collaboration with the University Medical Centre in Ljubljana.

Programme P4-0176: Molecular biotechnology: from the dynamics of biological systems to applications. Within the frame of this programme, research is being conducted in structural biochemistry, molecular biology and biomedicine. Research is focused on antibodies, primarily monoclonal, and their application in research, diagnostics and therapy. This also includes the research conducted by undergraduate and postgraduate students (mostly young researchers), while the scope of the programme also foresees research that cannot be carried out at BTC due to the nature of its work or lack of adequate equipment. Nationally and internationally, we are therefore an important partner to domestic and foreign academic institutions in our area of expertise. Collaboration with the National Institute of Chemistry.

Research projects

Project J1-4236: Planning, production and evaluation of biomimetic nanocomposite systems for efficient tissue regeneration. The proposed project is founded on the need to transfer basic knowledge into the development of modern products used for tissue regeneration in order to improve the quality of patients' lives and reduce the costs of treatment. The originality of the proposed project lies in a systematically designed production of nanocomposites with focus on nanofibres that are made using the electrospinning method. Another innovation is the approach to evaluating regeneration through the use of organotypic skin substitutes. Furthermore, new strategies will be integrated to enhance healing by implanting cells as a source of cytokines into biomimetic nanocomposites. Collaboration with the Faculty of Pharmacy at the University of Ljubljana.

Project J4-4123: Cysteine carboxypeptidase inhibitors as regulators of autoimmune and neurodegenerative processes. It is assumed that inhibitors of cysteine carboxypeptidase of cathepsin X inhibit autoimmune and neurodegenerative processes due to the specific role played by this enzyme in the regulation of integrin receptor LFA-1 and g-enolase. Different methods will be used within the scope of this project to obtain and select cathepsin X inhibitors that provide the specificity of action and minor cytotoxicity. By using delivery systems, such as biodegradable polymeric nanoparticles, we will provide for their controlled release and selective action in target cells. We intend to develop in vitro models of proliferating keratinocytes, T lymphocytes and neural cells that will depict the pathology of psoriasis and neurodegenerative diseases on which we plan to study the activity of selected inhibitors and delivery systems. The most promising anticathepsin compounds and formulations will be tested in vivo on animal specimens and their pharmacological action will be evaluated. Collaboration with the Faculty of Pharmacy at the University of Ljubljana.

Project L3-4150: Systemic immune disorders in children and adolescents. Systemic immune disorders are among the most frequent chronic disorders in children and represent a major cause of short-term or long-term impairment. In addition to complications that may occur in adult population, those in paediatric population further include specific complications related to growth and development, vaccination in childhood and effects on the quality of a child's life. Research work is focused on the improvement of diagnostic procedures used for early identification of systemic immune-mediated diseases in children and their successful treatment. Collaboration with the University Medical Centre in Ljubljana.

Project J3-4195: The creation of a line of multipotent/pluripotent stem cells from adult human ovarian and testicular tissue: a prospect for reproductive and regenerative medicine. The goal of the research project is to isolate stem cells and create stem cell lines from adult ovarian and testicular tissue. Following enzymatic decomposition of tissue, cell suspension will be used to isolate pluripotent stem cells, which are similar to embryonic stem cells, and multipotent mesenchymal stem cells. The isolation will be carried out using magnetic activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS). Attempts will be made to replicate cells in different culture media and on different substrates. The cell cultures prepared in this way will be evaluated by observing the formation of cell pools similar to embryoid bodies by immunocytochemical staining for typical markers, staining for alkaline phosphatase, using flow cytometry, identifying the expression of genes and by forming teratomas upon injection in mice having a suppressed immune system or, rather, with the presence of tissue from all germ lines (endoderm, mesoderm and ectoderm) in teratomas. If stem cell lines are successfully established, they will be differentiated into various types of somatic cells. Collaboration with the University Medical Centre in Ljubljana.