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Projects / Programmes source: ARIS

MOLECULAR INTERACTIONS

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Periods
January 1, 2015 - December 31, 2021
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
molecular interactions, pathogenesis, mycobacteria, listeria, immune system, virulence factors, MACPF/CDC protein family, lipids, lipid membranes, nanobiotechnology
Evaluation (rules)
source: COBISS
Evaluation of bibliographic research performance indicators according to ARIS methodology
Citations Citations for bibliographic records in COBIB.SI that are linked to records in citation databases
source: WoS source: Scopus source: COBISS
Researchers (33)
no. Code Name and surname Research area Role Period No. of publications
1.  55098  Maksimiljan Adamek  Biochemistry and molecular biology  Technical associate  2021  21 
2.  37453  PhD Saša Aden  Biochemistry and molecular biology  Researcher  2015 - 2021  37 
3.  15686  PhD Gregor Anderluh  Biochemistry and molecular biology  Head  2015 - 2021  980 
4.  16104  PhD Apolonija Bedina Zavec  Biotechnology  Researcher  2015 - 2021  154 
5.  18325  PhD Simon Caserman  Biochemistry and molecular biology  Researcher  2015 - 2021  108 
6.  31814  Urška Dečko    Technical associate  2020 - 2021  3 
7.  32068  PhD Ajda Flašker  Biochemistry and molecular biology  Researcher  2015 - 2016  24 
8.  26055  PhD Gorazd Hribar  Biochemistry and molecular biology  Researcher  2015 - 2016  49 
9.  39711  Maja Jamnik    Technical associate  2019 - 2021  22 
10.  38255  PhD Andreja Kežar  Biochemistry and molecular biology  Researcher  2015 - 2021  47 
11.  35382  PhD Matic Kisovec  Biochemistry and molecular biology  Researcher  2015 - 2021  86 
12.  54671  Neža Koritnik  Biochemistry and molecular biology  Junior researcher  2020 - 2021  16 
13.  34603  PhD Mirijam Kozorog  Biochemistry and molecular biology  Researcher  2015 - 2021  34 
14.  00385  PhD Nada Kraševec  Biotechnology  Researcher  2015 - 2021  218 
15.  17276  Jelka Lenarčič    Technical associate  2015 - 2019  2 
16.  36425  PhD Tea Lenarčič  Biochemistry and molecular biology  Researcher  2015 - 2019  43 
17.  13627  PhD Franci Merzel  Computer intensive methods and applications  Researcher  2015 - 2016  219 
18.  23123  MSc Tatjana Milunović  Biotechnology  Technical associate  2015  28 
19.  34329  PhD Omar Naneh  Biochemistry and molecular biology  Junior researcher  2015  23 
20.  35544  PhD Neža Omersa  Biochemistry and molecular biology  Technical associate  2015 - 2021  29 
21.  55663  Tanja Peric    Technical associate  2021  4 
22.  50709  Nejc Petrišič  Biochemistry and molecular biology  Junior researcher  2018 - 2021  17 
23.  30762  PhD Katja Pirc  Biochemistry and molecular biology  Researcher  2016 - 2021  46 
24.  12048  PhD Marjetka Podobnik  Biochemistry and molecular biology  Researcher  2015 - 2021  330 
25.  55817  Andreja Prešern  Biochemistry and molecular biology  Junior researcher  2021  11 
26.  31915  PhD Nejc Rojko  Biochemistry and molecular biology  Researcher  2015  29 
27.  50612  Tina Snoj  Biochemistry and molecular biology  Junior researcher  2017 - 2021  21 
28.  38479  PhD Aleksandra Šakanović  Neurobiology  Technical associate  2016 - 2018  25 
29.  38473  Tomaž Švigelj    Technical associate  2016 - 2021  11 
30.  21684  Tea Tomšič    Technical associate  2015 - 2020  2 
31.  32008  PhD Saša Vrhovec Hartman  Biochemistry and molecular biology  Researcher  2018 - 2019  23 
32.  53612  Nika Žibrat  Biochemistry and molecular biology  Junior researcher  2019 - 2021  12 
33.  34459  PhD Simon Žurga  Pharmacy  Researcher  2017  25 
Organisations (1)
no. Code Research organisation City Registration number No. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  21,327 
Abstract
Molecular interactions are crucial for the majority of biological processes and fundamental features of interactions are preserved in all kingdoms of life. To understand the complexity and functionality of various biological processes, it is crucial to study the interactions between the involved molecules. The Molecular Interactions Programme Group will study direct molecular interactions of proteins in different biological contexts, with main emphasis on pathogenesis and the immune system. Our main goal will be to understand structural details of molecular interactions, plasticity of these interactions and consequently the protein function. We will focus on some of the most important virulence factors in human diseases such as tuberculosis, listeriosis, malaria, aspergillosis, as well as some of the most devastating diseases in agriculture like potato blight. From the theoretical point of view we will contribute to understanding of protein evolution and evolution of protein binding sites for various ligands. Specifically we will study i) mechanism of action of proteins from intracellular bacteria like Mycobacteria, Listeria and others and their potential involvement in pathogenicity, ii) mechanism of activity of MACPF/CDC superfamily of proteins and iii) evolution of small tightly folded binding modules based on known structures of protein toxins that damage membranes. We also plan to develop novel approaches for regulation of activities of proteins under study by systematically targeting their interactions with other molecules. Besides understanding the basic principles in functioning of proteins from selected biological systems, we will implement the acquired knowledge to either benefit the efforts of the medical and pharmaceutical approaches to fight diseases and also elsewhere in biotechnology where biological molecules are used to support technological processes. In addition, we will implement the knowledge and expertise obtained from our basic research into the nanobiotechnological applications such as novel approaches for preparation of proteins, synthetic biology of lipid membranes, use of proteins for nanobiotechnological applications and pharmacological applications of large protein complexes. The proposed research activities will be performed in the Laboratory for Molecular Biology and Nanobiotechnology at the National Institute of Chemistry. The laboratory combines knowledge, experiences and equipment for research of proteins, lipids and molecular interactions. The group has extensive experiences in protein production, purification and characterisation. The members of the programme group have developed some of the state-of-the-art approaches for studying molecular interactions. The obtained results will have important impact on plant, animal and human health, as well as industrial applications involving proteins.
Significance for science
Studies of molecular interactions of the crucial protein virulence factors follow the research priorities of H2020 Health theme and that of the National Research Program (Health and Life Sciences). The main focus of the proposed research programme is molecular and mechanistic details of protein virulence factors. We expect that the outcoming results of this proposal will be important for the development of science in the following areas: 1. Studies of superfamilies of MACPF/CDC, actinoporin-like proteins and cyclic nucleotide binding proteins and their binding partners will increase understanding of molecular mechanisms of some of the most pressing diseases of the modern world like listeriosis, tuberculosis, malaria and potato blight. An improved understanding of molecular events that are basis for pathogenic effects will allow better design of intervention strategies. 2. Besides the importance of understanding the biological role and mechanism of action of the proteins during their pathogenesis, we also aim to contribute to better understanding of basic physical, chemical and thermodynamic features of these molecules. For example, conformational changes in molecules are at the heart of the most of the biological processes and are usually timed to interactions with other molecules or certain changes in the environmental conditions like temperature or pH. In spite of many studies done to date, for many proteins the presence of various potential ensembles of the same protein molecule but of different conformations, and the timing of the existence of these specific conformations, is still an enigma. In our studies we will use different model systems including proteins either involved in different allosteric enzymatic reactions or in lipid membrane pore formation, which are all processes where large conformational changes are expected. We will try to explain which parts in the structures of these molecules and to what extent are responsible for their conformational variability. This knowledge will contribute to better understanding of the basic physical principles of molecular features and the importance of conformational landscape and thus plasticity of biological molecules. Furthermore, by learning about specific parts of the structure that contribute most to the conformational variability, we will be able to predict potential regulation of these molecules by keeping them in limited conformational states (active or inactive) using mutagenesis or interaction with other molecules. 3. The detailed understanding of distribution of some of the actinoporin-like proteins will also allow deeper understanding of roles of so-called small secreted proteins. Small secreted proteins are defined as proteins smaller than 200 amino acids without transmembrane domains that are secreted from the fungal cells. Together with secondary metabolites they are considered a gold-mine for “omics” screening to reveal effectors important for fungal, or other organisms, survival and interactions with the environment. Although small secreted proteins were firstly defined in fungi to promote fungi-plant interactions they may be widespread. Actinoporin-like protein families perfectly fit the definition of small-secreted proteins and understanding of their distribution in nature will be crucial for understanding of various interactions of host organisms in the environment. Some of actinoporin-like proteins are highly secreted but they follow non-classical i.e. not signal peptide triggered protein secretion. 4. By the innovative use of molecular biology approaches, such as ribosomal display, coupled with other high-throughput approaches, for example next generation sequencing, we will better define binding regions for cell surface ligands for some of the virulence factors under study (cholesterol-dependent cytolysins, actinoporin-like proteins and cyclic nucleotide binding proteins). 5. Combination of various methodological approaches
Significance for the country
The proposed research activities are responsive and aligned with Slovenian and EU scientific development goals and are highly intersectorial. In the field of medical research Horizon 2020 prioritizes research addressing infectious and chronic diseases. By research targeting the populations at risk, children, pregnant women and elderly, the project also complies with the special EU focus on health of children, ageing population, and gender-related health. EU also promotes translational research, or the so-called “from bench-to-bedside” approach to gain practical benefits and improve the quality of life. Endorsement of “omics” based stratified approach and personalized medicine enables better understanding of determinants, risk factors and pathways of disease. Molecular interactions are posing the key to understand why individual drug is working for one but not for the other patient. For these reasons, the proposal is very timely and relevant to Slovenian and European science with an aim of enhancing overall quality of life. Laboratory for Molecular Biology and Nanobiotechnology has long-lasting fruitful collaborative contacts (over 15 years) with the local pharmaceutical industry (Lek, member of Sandoz, Novartis). Throughout the years the development of biosimilars in our laboratory (human granulocyte colony-stimulating factor (G-CSF), PEGylated G-CSF and erythropoietin) resulted in successful transfer of knowledge, leading to new green field investments in productive capacities and employment of highly qualified workers. Personnel trained in the laboratory currently support several important aspects of Lek production and development. The jointly developed biosimilars are now part of Sandoz biosimilars portfolio. Collaborative work with Lek on development of next generation of biopharmaceuticals and on FP6 project “Nanobiopharmaceuticals” resulted in accumulation of knowledge regarding protein modification and nanoformulation for advanced delivery systems. Development of biological tools for assessments of recombinant antibody potency and of approaches for bioprocess advancement further extends this fruitful collaboration. We maintain links with local and international industries. We collaborate with local biotechnological company (Bia Separations d.o.o.), the successful developer and producer of biomolecules purification systems through designing and producing model biomaterials needed for specific interaction with purification matrix and evaluation of its purification potency. We also signed and implemented contract with a foreign company (Oxford Nanopore Technologies) on specific biomolecule development. Tight contacts with industry are further extended by introduction and development of modern approaches for characterisation of proteins within the Slovenian research infrastructure. We believe this will contribute importantly to future development of molecular pharmacology expertise in the industrial partners and enable innovative solutions and personnel needed for new start-ups in Slovenia.   We will further aim to promote expertise and infrastructure for studying molecular interactions and thus increasing scientific visibility of the laboratory, NIC and Slovenian science as a whole. We have proven track record in establishing excellent facilities for molecular interactions analysis. Prof. Gregor Anderluh has established and is currently a head of the Infrastructural Centre for Molecular Interaction Analysis at the University of Ljubljana. This Infrastructural centre is unique in the region and so far allowed research work of 28 domestic and 7 foreign research groups from academia and industry. We will aim to integrate different expertise for molecular interaction analysis in Slovenia. Our short-term plan is to include laboratory in European networks of biophysical core facilities, which will be most likely established in the near future (we were invited to the firs Pan-European Core Facility Congress, where this ne
Most important scientific results Annual report 2015, interim report
Most important socioeconomically and culturally relevant results Annual report 2015, interim report
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