Projects / Programmes
Pharmaceutical biotechnology: Science for Health
January 1, 2015
- December 31, 2018
| Code |
Science |
Field |
Subfield |
| 4.06.00 |
Biotechnical sciences |
Biotechnology |
|
| 1.09.00 |
Natural sciences and mathematics |
Pharmacy |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 3.04 |
Medical and Health Sciences |
Medical biotechnology |
Biotechnology; Pharmacy; Nanotechnology; Cancer; Neurodegenerative diseases;Immune diseases; Proteases; Cathepsins; Inhibitors; Phage display; Allergy; TDP-43, FUS; Cytotoxicity; NK cells; T cells; Mimetics; Mimotopes; Lactic acid bacteria; Therapy; Diagnosis
Researchers (44)
Organisations (2)
Abstract
Success in prevention, diagnosis and therapy depends on the knowledge on molecular mechanisms leading to the development and progression of disease. Our goal is to determine molecular targets for development of new diagnostic and therapeutic strategies in cancer, neurological and immune diseases. In cancer we will investigate the role of proteolytic enzymes, known promoters of tumour invasion and metastasis. The inhibitors of cathepsin B, proved to impair malignant progression, will be translated to clinical studies and to veterinary medicine. By using the methods of virtual and experimental screening and directed chemical synthesis we will prepare synthetic inhibitors also to other enzymes. For their delivery to cells and tissues, the nanosystems will be used, whereas for delivery of recombinant proteins to gastrointestinal tract we will use lactic acid bacteria. In tumour diagnosis we will focus on search of markers for prediction of response to therapy.
A part of our cancer research will be directed towards anti-tumour immune response. We will test various immunomodulators of fungal and plant origin and synthetic compounds, based on their structure. An emphasis will be given to studies on cytotoxic T cells and natural killer (NK) cells, which are the most important mediators of anti-tumour immunity. The activation of cell cytotoxicity is driven by proteolytic enzymes which regulate some key steps, such as antigen processing and presentation and activation of granzymes in cytotoxic T cells and NK cells. We expect that the regulation of their function could enhance anti-tumour immune response.
Allergic immune response represents another field of our activities. By screening of peptide phage display libraries we will obtain mimetics of allergenic epitopes. Their binding will be tested on antibodies from sera from allergic patients. In this way we expect an improvement in the diagnosis and treatment of allergic diseases. Using the same screening procedure we will obtain also peptide inhibitors of grelin receptors and mimetics of leptin which may serve us to prepare peptidomimetics and lipopeptides, useful for treatment of obesity.
In Alzheimer's and Parkinson's disease we will study the role of gamma enolase as an important neurotrophic factor, which stimulates growth and proliferation of neurons and neuritogenesis. Since its neurotrophic activity is regulated by cathepsin X, its specific inhibitors, as well as peptide mimetics of the neurotrophic site, will be tested in vitro and in vivo in order to evaluate their neuroprotective properties. In patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration TDP-43 protein, involved in regulating transcription, splicing, miRNA biogenesis and RNA transport, will be studied. We will investigate also mutations in gene for FUS protein and GGGGCC hexanucleotide repeat expansion mutations of gene C9orf72, which are also associated with neurodegenerative diseases.
Significance for science
The research activities of the programme group are part of the advanced trends in science aimed at increasing our understanding of living processes and improving health care. Understanding the basic mechanisms of cell function as well as disturbances causing the development and progression of cancer, neurodegenerative and immune disorders is our major preoccupation. Besides understanding the mechanisms we wish to change them and to identify targets for development of new diagnostic and therapeutic strategies.
Cancer is a typical disease of modern society. Conventional therapeutic approaches, including surgery, chemotherapy and radiotherapy, have a limited range, and have to be supplemented by new approaches if we want to prolong the survival of cancer patients and improve their quality of life. New chemotherapeutics, directed against exceeded action of proteolytic enzymes, new delivery systems and understanding of molecular mechanisms of cytotoxicity of T cells and natural killer cells and the processes triggered by tumour cells to impair their cytotoxicity, enable additional opportunities for development of more effective anti-tumour therapies.
Neurodegenerative diseases represent another big burden for health in developed countries which is increasing due to longevity, since neurodegenerative diseases like cancer affect elder population. Despite half a century of advances in neuroscience there are no drugs that significantly improve the course of any neurodegenerative disorder. The discovery of new neurotrophic factors which promote protection and regeneration of neuronal cells, and their signalling pathways represent an advanced approach and enables new treatment strategies. Recent results of our and other groups, being published in respected journals, suggest an arising importance of RNA-related processes in etiology of neurodegenerative diseases. These studies will be upgraded by studying some of the most basic newly discovered processes, such as RNA toxicity and RAN translation, which will have far wider implications for understanding of neurodegenerative processes.
Immune diseases were a subject of our investigations also in the previous financing period. We determined the role of proteolytic enzymes in regulation of integrin receptors in immune cells, which achieved a confirmation in scientific community. We will extend our studies on allergic diseases, a part of immune diseases which significantly expanded during last years. The causes for the increase and the mechanisms are not yet known, our studies should contribute to better detection of allergens in individual patients.
The achievements of the members of the programme group are reflected in numerous publications and citations and show our significant contribution to universal understanding. Moreover, our group is introducing into our research area the most recent biotechniques and analytical methods. The collaboration with other researchers in Slovenia and worldwide guarantees rapid transfer of knowledge, good science and valuable applications also in future.
Significance for the country
In developed countries medical treatment, health care and prevention are important elements in the socio-economic development of individuals and the society, and every step towards better health is important. Although cancer, neurodegenerative and immune diseases are receiving an outstanding input of funds for basic and clinical research, they still represent a great burden for health systems. Only new approaches based on the investments to basic and clinical research in this field may result in progress in treatment, improve the quality of life of patients and reduce the financial burden for health systems. Furthermore, the activities of the programme group will also contribute to all levels of university education. They will enable students to acquire new knowledge and will provide opportunities for diploma, master and doctoral training in different research fields. The latter will be possible since the members of the programme group are involved in the pedagogical process at public universities and at the Jožef Stefan Postgraduate School. The results of the programme will also foster our collaboration with excellent research groups, increasing knowledge exchange and opportunities to obtain new European and other funds for financing our science.
The results of the proposed programme will make possible the development of new technologies and products, which will be economically interesting for pharmaceutical and biotechnological companies. They can also serve as a basis for establishing new start-up companies. In Slovenia and the European Union, biotechnology, biomedicine and pharmacy constitute a leading scientific and economic priority. The pharmaceutical industry has exhibited outstanding growth in recent years and the implementation of new products, either original or generic, constitutes the main driving force. Only the scientific knowledge arising from top class research in this field, to which our proposed project will contribute, may result in products with high added value increasing the competitiveness of companies in Slovenia and Europe. Besides potential new drugs, the project will employ the most recent methods and techniques, which can easily be adopted by industrial laboratories. The experience of the programme group on patent protection of applicable research results and established co-operation with industrial partners will guarantee successful transfer of the knowledge and the results of the proposed programme to users in industry and clinics.
Most important scientific results
Annual report
2015,
2016,
2017,
final report
Most important socioeconomically and culturally relevant results
Annual report
2015,
2016,
2017,
final report
