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Projects / Programmes source: ARRS

Toxins and Biomembranes

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Periods
January 1, 2020 - December 31, 2025
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 
3.04  Medical and Health Sciences  Medical biotechnology 
Keywords
Venom, toxin, phospholipase A2, pore-former, mechanism, cancer, apoptosis, lipid signalling, lipid metabolism, phylogenomics, gene transfer, polygenic trait, membrane, raft, haemostasis, neurodegeneration, anticoagulant, biofuel, nanomedicine, biomarker, bioinsecticide, Saccharomyces cerevisiae
Evaluation (rules)
source: COBISS
Points
8,886.9
A''
1,910.88
A'
4,996.74
A1/2
6,123.47
CI10
14,111
CImax
617
h10
52
A1
32.42
A3
10.78
Data for the last 5 years (citations for the last 10 years) on March 30, 2023; A3 for period 2017-2021
Data for ARRS tenders ( 04.04.2019 – Programme tender , archive )
Citations Citations for bibliographic records in COBIB.SI that are linked to records in citation databases
source: WoS source: Scopus source: COBISS
Database Linked records Citations Pure citations Average pure citations
WoS  787  23,529  18,832  23.93 
Scopus  807  25,628  20,746  25.71 
Researchers (36)
no. Code Name and surname Research area Role Period No. of publications
1.  53554  Tadeja Bele  Biochemistry and molecular biology  Junior researcher  2020 - 2023  9 
2.  24290  PhD Matej Butala  Biochemistry and molecular biology  Researcher  2020 - 2023  225 
3.  55138  PhD Mauro Danielli  Biochemistry and molecular biology  Junior researcher  2021 - 2023  16 
4.  11155  PhD Damjana Drobne  Biology  Researcher  2020 - 2023  822 
5.  32099  PhD Maja Grundner  Biochemistry and molecular biology  Researcher  2020 - 2023  27 
6.  15639  PhD Gregor Gunčar  Biochemistry and molecular biology  Researcher  2020 - 2023  250 
7.  53283  Maja Hostnik  Biochemistry and molecular biology  Researcher  2020 - 2023  11 
8.  50498  Adrijan Ivanušec  Biochemistry and molecular biology  Junior researcher  2020 - 2023  23 
9.  38200  PhD Eva Jarc Jovičić  Biochemistry and molecular biology  Researcher  2020 - 2023  56 
10.  35369  PhD Veno Kononenko  Biochemistry and molecular biology  Researcher  2020  55 
11.  15587  Igor Koprivec    Technician  2020 - 2023  0 
12.  07673  PhD Dušan Kordiš  Biochemistry and molecular biology  Researcher  2020 - 2023  214 
13.  55063  Špela Koren  Biochemistry and molecular biology  Junior researcher  2021 - 2023  14 
14.  00412  PhD Igor Križaj  Biochemistry and molecular biology  Principal Researcher  2020 - 2023  696 
15.  53699  Amela Kujović  Biochemistry and molecular biology  Technician  2020  16 
16.  18802  PhD Adrijana Leonardi  Biochemistry and molecular biology  Researcher  2020 - 2023  139 
17.  06994  PhD Peter Maček  Biochemistry and molecular biology    2020 - 2023  524 
18.  39242  PhD Nina Mikec  Biochemistry and molecular biology  Researcher  2020 - 2021  19 
19.  35319  PhD Mojca Ogrizović  Biochemistry and molecular biology  Researcher  2021  35 
20.  33683  Nina Orehar    Technician  2020 - 2023  5 
21.  37465  PhD Sabina Ott Rutar  Biochemistry and molecular biology  Junior researcher  2020  11 
22.  39090  PhD Anastasija Panevska  Biochemistry and molecular biology  Researcher  2020 - 2023  46 
23.  51231  Anja Pavlin  Biochemistry and molecular biology  Junior researcher  2020 - 2023  21 
24.  23575  PhD Miha Pavšič  Biochemistry and molecular biology  Researcher  2020 - 2021  177 
25.  20213  PhD Toni Petan  Biochemistry and molecular biology  Researcher  2020 - 2023  161 
26.  20653  PhD Uroš Petrovič  Biochemistry and molecular biology  Researcher  2020 - 2023  274 
27.  55861  Larisa Lara Popošek  Biochemistry and molecular biology  Junior researcher  2021 - 2023  2 
28.  54618  Kity Požek  Biochemistry and molecular biology  Technician  2020 - 2023  18 
29.  04570  PhD Jože Pungerčar  Biochemistry and molecular biology  Researcher  2020 - 2023  318 
30.  37504  Neža Repar  Biology  Technician  2020 - 2023  30 
31.  15328  PhD Kristina Sepčić  Biochemistry and molecular biology  Researcher  2020 - 2023  699 
32.  33137  PhD Matej Skočaj  Biochemistry and molecular biology  Researcher  2020 - 2023  96 
33.  21553  PhD Jernej Šribar  Biochemistry and molecular biology  Researcher  2020 - 2023  106 
34.  06905  PhD Tom Turk  Biochemistry and molecular biology  Researcher  2020 - 2023  603 
35.  54712  Gašper Žun  Biochemistry and molecular biology  Junior researcher  2020 - 2023  22 
36.  15640  PhD Vera Župunski  Biochemistry and molecular biology  Researcher  2020 - 2023  167 
Organisations (3)
no. Code Research organisation City Registration number No. of publications
1.  0103  University of Ljubljana, Faculty of Chemistry and Chemical Technology  Ljubljana  1626990  21,909 
2.  0106  Jožef Stefan Institute  Ljubljana  5051606000  85,660 
3.  0481  University of Ljubljana, Biotechnical Faculty  Ljubljana  1626914  64,564 
Abstract
The research programme “Toxins and biomembranes” is an evolving platform initiated to study toxins, primarily those that interact with biological membranes and consequences that arise from these interactions. It sprouted to areas of mammalian physiology affected by the toxins, to obtain insight into the function and dysfunction of their mammalian orthologues. The activity of the programme group (PG) is divided into six work packages (WPs) that are autonomous to some extent nevertheless comprehensively intertwined, complementary and vertically connected (e.g. on cancer, neurodegenerative disease and antimicrobial studies). WP1 is focused on the study of animal venoms, their composition, mode of action and protection. By description of molecular basis of action of toxins, we will continue revealing basic mechanisms of protein traffic in cells, regulation of endo/exocytosis, and mitochondrial functions. The latter may help at early diagnosis of Alzheimer`s disease and its treatment. A very promising line of research is also development of innovative anticoagulants to treat venous thromboembolism safely. Under WP2 our knowledge of toxic secreted phospholipases A2 action is employed to study lipid metabolism and signalling. Study of function of lipid droplets, emerging as new organelles, is the major topic here, focused in particular to fight cancer. WP3 aims to investigate molecular mechanisms of interaction of membrane-binding proteins, compounds that bind to certain types of nicotinic acetylcholine receptors and consequences of these interactions on membrane physical properties and on cell physiology. An important part of research is devoted to possible use of membrane-binding proteins in biomedical and biotechnological applications, for example in development of markers of membrane lipids and domains, development of new anticancer drugs and new bioinsecticides. It is becoming clear that the interaction of nanoparticles (NPs) with cells, primarily with biological membranes, is extremely important for human health. To this and to exploitation of NPs in medical applications we dedicate our activities under WP4. In WP5 we will investigate diverse genome components, including those of parasites and viruses. Therapeutic potential of antimicrobial peptides as new antimicrobials will be explored. In WP6, we use yeast Saccharomyces cerevisiae as a central eukaryotic model organism to study importance of inter-organelle communication in crosstalk between lipid and central carbon metabolism, and to develop new methodology and biotechnological applications of polygenic trait analysis. Principal goal of our PG is therefore to acquire new facts about mammalian pathophysiology aiming to improve human and animal health. In addition, we will try to create ways to biotechnologically exploit our discoveries and to develop new methods. Many members of the PG are engaged in teaching at under- and post-graduate level, so an important mission of our PG is also to communicate the cutting-edge science to students.
Significance for science
The research programme “Toxins and biomembranes” is a platform, which was initially shaped to exhaustively address toxins that primarily interact with biological membranes – their protein, lipid or carbohydrate constituents – and the consequences that arise from these interactions. Gradually it expanded to some areas of mammalian physiology, in which the mammalian orthologues of toxins are implicated, exploiting the results obtained by the toxins. Most recently, it included research of interaction between nanomaterials and biological membranes, from basics to medical applications. Our programme group (PG) is successfully evolving in six main directions, six research areas of supreme relevance for human and animal health and biotechnological development. (1) We are studying animal venoms, their composition, mode of action and protection. By description of molecular basis of action of toxins, we are revealing basic mechanisms of protein traffic in cells, regulation of endo/exocytosis, and mitochondrial functions. We are using toxins to improve understanding and treatment or diagnosis of neurodegenerative diseases, such as Alzheimer`s disease, and cardio-vascular diseases, such as deep vein thrombosis and pulmonary embolism. We develop innovative procedures to protect from venoms and toxins. (2) We are studying lipid metabolism and signalling also by exploiting the knowledge gained through our research of toxic secreted phospholipases A2, orthologues of mammalian enzymes that are important factors in inflammation and immunity. We focus on the interplay between phospholipid metabolism and fat storage in lipid droplets. These newly recognized organelles are emerging as central hubs regulating intracellular signalling cascades, metabolic pathways and cellular stress responses. In particular, by targeting lipid droplet metabolism and signalling we aim to reduce the resilience of aggressive cancer cells and inhibit tumour growth. Understanding the regulation of these processes is critical for advancing treatment and diagnosis of diseases and metabolic disorders associated with lipid accumulation, including different types of cancer, type 2 diabetes and obesity. (3) We are investigating molecular details of interaction between proteins and membranes, and compounds that bind to cholinesterases and to certain types of nicotinic acetylcholine receptors. In this way, we are exploring possibilities of the use of membrane-binding proteins in biomedical and biotechnological applications, for example at development of markers of membrane lipids and domains, development of new anticancer drugs and new bioinsecticides. (4) It is becoming clear that the interaction of nanoparticles (NPs) with cells, primarily with biological membranes, is extremely important for different applications supporting human health. We study basic interactions between NPs and biological systems, as well as nanomaterials as drug or vaccine carriers that facilitate controlled crossing of the cell membrane, and their usage in diagnostic or therapeutic applications for cancer and neurodegeneration, linking different work packages of our PG. (5) Animal toxins represent a very good model system to study adaptive evolution, cis-regulatory evolution, evolution of three-dimensional protein structures, emergence of new biological functions and underlying changes at the genomic level. We are exploring for example diverse genome components, including those of parasites and viruses, and, of the highest medical relevance, therapeutic potential of antimicrobial peptides. (6) Biomembranes are present in all life forms, and are especially crucial in eukaryotes where they delineate cellular compartments. We use yeast Saccharomyces cerevisiae as a central eukaryotic model organism to study importance of inter-organelle communication in crosstalk between lipid and central carbon metabolism, and to develop new methodology and biotechnological applications of polygenic trait analysis. Studi
Significance for the country
Research of the programme group (PG) does not only contribute to the world’s body of knowledge, but also has practical values. Most advanced in this respect are two projects. The first is developing proteinaceous cytolytic complexes, based on aegerolysin proteins, as potent and selective insecticides against economically most important coleopteran pests. The results of this project have already been protected by an international patent application (PCT/EP2017/074877). Promisingly, a very strong international company expressed an interest in testing our proteins on large spectrum of plant pests. The second project is addressing the deficit in the therapy of venous thromboembolism (VTE) by developing a new line of selective inhibitors of the intrinsic blood coagulation pathway based on structurally original snake venom anticoagulant protein. Here as well, one of the biggest pharmaceutical corporations joined us on the project. Interest of the European biotech / IPM companies is a good prospect to capitalize part our research. Besides these two projects, several other studies give promise of development towards applications with commercial value. To this end, we will continue to develop, together with our colleagues from the University Clinical Centre in Ljubljana, procedures for more effective and safe post-envenomation treatment of patients, alternative antitumor drugs (?7 nAChR antagonists to treat lung adenocarcinoma), and antithrombotic agents (snaclecs-based antithrombotics for interventional cardiology and angiology). Treatment and diagnosis of neurodegenerative diseases, such as Alzheimer’s disease, will be tackled by further development of nano-materials-supported blood biosensors based on AChE/BChE analysis. Development of these and other projects important for human health and well-being will be boosted through intensive participation in SRIP Health – Medicine, which is among the nine strategic areas in Slovenia recognized by the government to lead the way towards the social and economic transformation in Slovenia. Active and Healthy Aging is one of strategic areas in SRIP Health – Medicine. One of its focuses is Diagnostics of Neurotoxicity and Neurodegeneration as well as New products and services for Aging population. A member of our PG is thus leading the focusing area “Active Healthy Aging” and she will continue to intensively interconnect the activities within the PG with and SRIP Health – Medicine and support translation of new knowledge into innovation and vice versa. Polygenic trait analysis and allele replacement is a complementary approach to traditional metabolic engineering that enables construction of strains with a combination of desirable traits, including some that are unattainable using traditional metabolic engineering approaches. In this way, we have been developing new industrial strains of microorganisms. For example, yeast strains with increased lipid synthesis for the production of biofuels that will play an important role at supplying alternative energy sources, enabling much lower dependence on fossil fuels. A very important aspect is the acquisition of cutting-edge technologies, especially in the areas of functional genomics, proteomics and genomic biology. We upgrade and develop research methods, such as 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. We create new methods, for example to identify protein complexes interacting with specific genomic loci directly in bacteria. This method will enable identification of transcription factors bound to selected promoters, a prerequisite to design and synthesize molecules to block development of antibiotic resistance and expression of virulence factors at the transcription level in pathogens. The PG represents a conti
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