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Projects / Programmes source: ARIS

Toxins and Biomembranes

Periods
Research activity

Code Science Field Subfield
1.05.00  Natural sciences and mathematics  Biochemistry and molecular biology   
4.06.00  Biotechnical sciences  Biotechnology   

Code Science Field
B000  Biomedical sciences   

Code Science Field
1.06  Natural Sciences  Biological sciences 
Keywords
Toxin, presynaptic neurotoxicity, cytotoxicity, haemorrhagicity, phospholipase A2, metalloproteinase, pore-former,mechanism of action, receptor, cancer, apoptosis,lipid signalling, phylogenomic, horizontal gene transfer, polygenic traits,lipid membrane, lipid raft, cholinesterase inhibitor, biofuels
Evaluation (rules)
source: COBISS
Researchers (37)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  53554  Tadeja Bele  Biochemistry and molecular biology  Junior researcher  2019  12 
2.  34328  Špela Bordon  Biochemistry and molecular biology  Junior researcher  2015 - 2018 
3.  24290  PhD Matej Butala  Biochemistry and molecular biology  Researcher  2015 - 2019  236 
4.  11155  PhD Damjana Drobne  Biology  Researcher  2019  863 
5.  25974  PhD Cene Gostinčar  Biotechnology  Researcher  2018  335 
6.  32099  PhD Maja Grundner  Biochemistry and molecular biology  Researcher  2017 - 2019  34 
7.  15639  PhD Gregor Gunčar  Biochemistry and molecular biology  Researcher  2015 - 2019  262 
8.  50498  PhD Adrijan Ivanušec  Biochemistry and molecular biology  Junior researcher  2017 - 2019  27 
9.  38200  PhD Eva Jarc Jovičić  Biochemistry and molecular biology  Junior researcher  2015 - 2019  67 
10.  34435  Minca Klobčar  Biology  Junior researcher  2015 - 2016 
11.  35369  PhD Veno Kononenko  Biochemistry and molecular biology  Researcher  2019  68 
12.  15587  Igor Koprivec    Technical associate  2015 - 2019 
13.  07673  PhD Dušan Kordiš  Biochemistry and molecular biology  Researcher  2015 - 2019  215 
14.  00412  PhD Igor Križaj  Biochemistry and molecular biology  Head  2015 - 2019  725 
15.  50856  Beti Kužnik  Biochemistry and molecular biology  Technical associate  2018 
16.  18802  PhD Adrijana Leonardi  Biochemistry and molecular biology  Researcher  2015 - 2019  156 
17.  06994  PhD Peter Maček  Biochemistry and molecular biology  Retired researcher  2015 - 2019  523 
18.  26460  PhD Mojca Mattiazzi Ušaj  Biochemistry and molecular biology  Researcher  2015  62 
19.  33136  PhD Miha Mikelj  Pharmacy  Junior researcher  2015  19 
20.  35371  PhD Maruša Novak  Biotechnology  Researcher  2015 - 2018  34 
21.  33324  PhD Jernej Oberčkal  Biochemistry and molecular biology  Junior researcher  2015  44 
22.  35372  PhD Davor Obradović  Natural sciences and mathematics  Junior researcher  2015 - 2017  14 
23.  35319  PhD Mojca Ogrizović  Biochemistry and molecular biology  Technical associate  2015 - 2017  35 
24.  33683  Nina Orehar    Technical associate  2015 - 2019 
25.  37465  PhD Sabina Ott Rutar  Biochemistry and molecular biology  Junior researcher  2016 - 2019  11 
26.  39090  PhD Anastasija Panevska  Biochemistry and molecular biology  Junior researcher  2016 - 2019  55 
27.  51231  PhD Anja Pavlin  Biochemistry and molecular biology  Junior researcher  2018 - 2019  26 
28.  23575  PhD Miha Pavšič  Biochemistry and molecular biology  Researcher  2015 - 2019  203 
29.  20213  PhD Toni Petan  Biochemistry and molecular biology  Researcher  2015 - 2019  177 
30.  20653  PhD Uroš Petrovič  Biochemistry and molecular biology  Researcher  2015 - 2019  292 
31.  04570  PhD Jože Pungerčar  Biochemistry and molecular biology  Researcher  2015 - 2019  320 
32.  37504  PhD Neža Repar  Biology  Junior researcher  2019  31 
33.  15328  PhD Kristina Sepčić  Biochemistry and molecular biology  Researcher  2015 - 2019  729 
34.  33137  PhD Matej Skočaj  Biochemistry and molecular biology  Researcher  2018 - 2019  107 
35.  21553  PhD Jernej Šribar  Biochemistry and molecular biology  Researcher  2015 - 2019  108 
36.  06905  PhD Tom Turk  Biochemistry and molecular biology  Researcher  2015 - 2019  619 
37.  15640  PhD Vera Župunski  Biochemistry and molecular biology  Researcher  2015 - 2019  185 
Organisations (3)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0103  University of Ljubljana, Faculty of Chemistry and Chemical Technology  Ljubljana  1626990  23,083 
2.  0106  Jožef Stefan Institute  Ljubljana  5051606000  90,682 
3.  0481  University of Ljubljana, Biotechnical Faculty  Ljubljana  1626914  66,295 
Abstract
The main purpose of the proposed programme is acquisition of new knowledge about mammalian pathophysiology with the aim to improve human and animal health. Part of the activities will be dedicated also to acquisition of economically important bioproducts using microorganisms. The emphasis of our research will be on toxins that interfere with nervous and haemato-vascular system. We will deepen our study of the molecular mechanism of action of neurotoxic secreted phospholipases A2 (sPLA2s) and expand it by using these molecules in the research of novel pathways of proteins across cellular membranes, of regulation of endo- and exocytosis and to study the functioning and regulation of their human orthologues in the cytosol and in mitochondria. An important goal is to find new possibilities to treat some serious neurodegenerative diseases. In the area of research of molecular organisation of membrane lipid micro- and nanodomains we will continue to study the specific interactions of pore-forming proteins with lipids in artificial and natural cell membranes, and mechanisms of their effects on remodelling and functionality of the membranes. We will extend our research also on genotoxic cytotoxins CdtABC, powerful bacterial virulent factors. We will continue to study pharmacologically interesting compounds from sea organisms, primarily sponges, with antibacterial and anticholinesterase activity. These are potential leads to develop novel antibiotics or pharmaceutics to control the cholinergic system. We will check also potential inhibitory effects of sponge poly-alkylpyridinium salts on tumour cell proliferation. We will study the role of lipid metabolism and signalling in human health and disease. Alterations in lipid metabolism are crucial determinants of the most wide-spread modern diseases in humans, such as metabolic syndrome, diabetes, cardiovascular disease and cancer. We will study the role of sPLA2 enzymes in whole-body fatty acid metabolism and lipid accumulation. We expect to reveal important relationships between membrane remodelling, lipid metabolism and lipid droplet amount and composition primarily within tissues in which excessive accumulation of lipids is critical for pathology of a particular disease. We will explore and provide new insights into the origin, evolution and functional diversification of diverse components in the genomes of prokaryotes and eukaryotes, impact of large ecological catastrophes on genome evolution and the origin and evolution of protein families that acquired important regulatory roles. Among the promising alternative energy and chemical industry sources are lipids, produced by microorganisms from lignocellulosic biomass. We have developed an improved method to detect causal genes for polygenic traits, such as lipid storage capacity, and using it, we will study the capabilities of strains of industrial microorganisms (mainly yeasts) for transformation of lignocellulosic biomass into, for example, biodiesel.
Significance for science
Our research may be divided into toxinological studies, investigations of pore-forming proteins, lipids and health, high-throughput yeast genetics, genome analysis and development of new methods. Most of the studies have already been undertaken in the previous period, but they will be deepened and expanded. Such efforts are justified by the actuality of these fields and their importance for the improvement of human health and development of new biotechnological processes, as well as by a high scientific relevance of our results so far. We have published them in some of the most prestigious journals, such as Nature, PNAS and MBE. Our publications are highly cited, and their influence is illustrated in invitations for speakers at the high-rank conferences, for preparing review articles, to the editorial boards of scientific journals, and for scientific and organising committees of the well-reputed meetings. All of these reflect the visibility and establishment of our group in the international scientific community. In toxinology, we will continue to focus on the analysis of molecular mechanisms of action of the various components of animal venoms, toxins and other substances that interfere with biological membranes, to develop new molecular tools for research in physiology and medicine, to develop innovative biological agents (antithrombotics, cytostatics, analgetics, immunotoxins), and defence against venoms and toxins (detection and therapy, both connected to the medicine and bioterrorism). The toxins studied act in different ways and cell types; including neurotoxins, cytolysins, esp. pore-forming proteins, and components of the toxins affecting haemostasis. Our results will importantly contribute to the research of structure and dynamics of biological membranes, intracellular protein trafficking and finding new approaches for the treatment of blood and vascular diseases, such as acute myocardial infarction, pulmonary embolism and stroke, and to explain and treat certain neuropathies, such as Zellweger syndrome, Alzheimer's and Parkinson's disease. Secreted phospholipases A2 activate intracellular signalling cascades and are important factors in lipid metabolism in mammals. Knowing the regulation of these processes is critical for the understanding of certain diseases and metabolic disorders, including cancer, type 2 diabetes and obesity. Studies of polygenic traits will enable a new breakthrough in genetics and its wider use in the development of a new generation of industrial microorganisms. Studies of polygenic traits in microorganisms will also represent valuable models for study of such traits in human, also in human medicine as most deseases are polygenic. Investigations of diverse genome components (transposable elements, newly formed genes, functionally diversified genes and multigene families) are relevant to a number of important questions of evolutionary and regulatory genomics. They will provide new insights into the origin and evolution of different genome components, and the acquisition of important biological roles in the novel genes and functionally diversified protein superfamilies.
Significance for the country
Research of the programme group (PG) not only contributes to the world’s body of knowledge, but also have practical values. Among these, we will continue to develop processes for the production of effective and safe antidotes, as well as alternative antitumour, anticoagulant and antithromotics agents. Yeast strains with increased lipid synthesis for the production of biofuels will be developed. In the future, new generation industrial microorganisms will play an important role at supplying energy sources, enabling thus much lower dependence on fossil fuels, as well as other bio-products. A very important aspect is the acquisition of cutting-edge technologies, esp. in the areas of functional genomics, proteomics and genomic biology. We upgrade and develop research methods, e.g., the process of automatic quantification of colonies in yeast phenomics and methods for the study of interactions between proteins and lipid membranes by SPR, as well as participate in the development of novel bioinformatic tools for analysis of the results of genomic experiments. The PG represents a continuous source of educated personnel, trained to work with the latest research techniques in biochemistry, pharmacology, molecular biology and genetics. Our research is also important for the Slovenian economy, both for biotechnology-based small businesses enterprises, such as Genialis, Bia and Acies Bio, and for the large pharmaceutical company, Lek Sandoz, intensively cooperating with the PG. Our activity is important for health. Together with the University Clinical Centre of Ljubljana we are continuing to develop new agents to control haemostasis and for haematological diagnosis, with the research of markers for antiphospholipid syndrome and expanding our investigations into clinically relevant bacterial pathogens (e.g., Aggregatibacter actinomycetemcomitans). Very important is also our contribution to the education of young researchers and students. Most of the PG members is intensively involved in teaching, both at the under- and postgraduate levels, at the Universities of Ljubljana, Maribor and Nova Gorica, and at the Jozef Stefan International Postgraduate School. Some members participate in the reformation of university programmes in accordance with the Bologna declaration and their (re)accreditation. With numerous publications in highly cited international scientific journals, lectures and participation in the organisation of international scientific meetings, our PG undoubtedly contributes to the promotion of Slovenian science, this important part of the national culture and identity, in the world. The PG has established a number of international collaboration with prominent researchers and institutions around the world, and always tends to establish new contacts. Our members will continue with their functions in international associations and editorial boards of journals, which will further strengthen the national identity, visibility and reputation of Slovenia in the world. Part of our research will contribute to the understanding and preservation of the rich natural heritage of our native fauna and microbiota, and to the understanding of its high biodiversity.
Most important scientific results Annual report 2015, interim report, final report
Most important socioeconomically and culturally relevant results Annual report 2015, interim report, final report
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