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Projects / Programmes source: ARIS

Molecular Interactions

Periods
January 1, 2022 - December 31, 2027
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
1.06  Natural Sciences  Biological sciences 
3.04  Medical and Health Sciences  Medical biotechnology 
Keywords
pathogenesis, Listeria, virulence factors, MACPF/CDC protein family, actinoporins, Nep1-like proteins, lipids, glycosylinositol phosphorylceramides, lipid membranes, filamentous plant viruses, nanobiotechnology, nanopores, sensing, molecular interactions, structural biology, cryo-electron microscopy
Evaluation (rules)
source: COBISS
Points
3,885.87
A''
719.42
A'
1,850.48
A1/2
2,802.35
CI10
18,742
CImax
6,816
h10
46
A1
13.94
A3
6.73
Data for the last 5 years (citations for the last 10 years) on July 14, 2024; A3 for period 2018-2022
Data for ARIS tenders ( 04.04.2019 – Programme tender , archive )
Database Linked records Citations Pure citations Average pure citations
WoS  343  19,515  17,605  51.33 
Scopus  344  22,555  20,546  59.73 
Researchers (27)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  55098  Maksimiljan Adamek  Biochemistry and molecular biology  Technical associate  2022  21 
2.  15686  PhD Gregor Anderluh  Biochemistry and molecular biology  Head  2022 - 2024  980 
3.  16104  PhD Apolonija Bedina Zavec  Biotechnology  Researcher  2022 - 2024  154 
4.  55978  Primož Bembič  Biochemistry and molecular biology  Technical associate  2022 - 2024 
5.  18325  PhD Simon Caserman  Biochemistry and molecular biology  Researcher  2022 - 2024  108 
6.  54368  PhD Ana Crnković  Biochemistry and molecular biology  Researcher  2022 - 2024  44 
7.  29520  PhD Kristina Eleršič Filipič  Biochemistry and molecular biology  Researcher  2023 - 2024  97 
8.  39711  Maja Jamnik    Technical associate  2022 - 2024  22 
9.  50722  Luka Kavčič    Technical associate  2022 - 2024  32 
10.  38255  PhD Andreja Kežar  Biochemistry and molecular biology  Researcher  2022 - 2024  46 
11.  35382  PhD Matic Kisovec  Biochemistry and molecular biology  Researcher  2022 - 2024  86 
12.  54671  Neža Koritnik  Biochemistry and molecular biology  Junior researcher  2022 - 2024  16 
13.  34603  PhD Mirijam Kozorog  Biochemistry and molecular biology  Researcher  2022 - 2024  34 
14.  00385  PhD Nada Kraševec  Biotechnology  Researcher  2022 - 2024  217 
15.  57301  Aljoša Marinko    Technical associate  2023 - 2024 
16.  35544  PhD Neža Omersa  Biochemistry and molecular biology  Researcher  2022  29 
17.  55663  Tanja Peric    Technical associate  2022 - 2024 
18.  50709  Nejc Petrišič  Biochemistry and molecular biology  Researcher  2022 - 2024  17 
19.  30762  PhD Katja Pirc  Biochemistry and molecular biology  Researcher  2022 - 2023  46 
20.  12048  PhD Marjetka Podobnik  Biochemistry and molecular biology  Researcher  2022 - 2024  329 
21.  55817  Andreja Prešern  Biochemistry and molecular biology  Junior researcher  2022 - 2024  11 
22.  57988  Matija Ruparčič  Biochemistry and molecular biology  Junior researcher  2023 - 2024 
23.  56954  Gregor Spruk  Biochemistry and molecular biology  Junior researcher  2022 - 2024 
24.  50369  Gašper Šolinc    Technical associate  2022 - 2024  23 
25.  38473  Tomaž Švigelj    Technical associate  2022  11 
26.  57067  Liza Ulčakar  Biochemistry and molecular biology  Junior researcher  2023 
27.  53612  Nika Žibrat  Biochemistry and molecular biology  Junior researcher  2022 - 2024  12 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  21,237 
Abstract
Interactions between molecules are crucial for majority of biological processes. The main goal of the proposed research activities within the programme "Molecular Interactions" is to address molecular interactions of important protein effectors and, consequently, their function in microbial pathogenesis. We will focus on some of the most important virulence factors in human diseases such as listeriosis, as well as some of the most devastating diseases in agriculture like potato blight. We will study proteins that are able to damage cellular membranes in complex multistep mechanisms. Additionally, we will look into evolution of small membrane-binding domains and in particular of binding sites for various lipids found in plasma membrane. Specifically we will study i) molecular mechanism of lipid membrane damage induced by Nep1-like proteins, ii) molecular interactions in MACPF/CDC protein family and how cholesterol is recognised by CDCs, iii) molecular evolution of actinoporin-like proteins, iv) molecular interactions and mechanistic features of economically important filamentous plant viruses, v) properties of novel protein nanopores for sensing applications based on various protein scaffolds, and vi) protein nanopores and model membranes for synthetic biology applications. Besides providing molecular details on mechanism of action of selected biological systems, we will also implement the acquired knowledge to design novel medical and pharmaceutical approaches to fight diseases, nanobiotechnological applications such as novel approaches for preparation of proteins, synthetic biology of protein nanopores and lipid membranes, and technological applications of large protein complexes, such as protein nanopores or virus like particles. The programme group at the Department for Molecular Biology and Nanobiotechnology at the National Institute of Chemistry combines knowledge, experiences and equipment for preparation and analysis of proteins, lipids and their molecular interactions and mechanism of action by implementing complementary tools, such as biochemical and biophysical approaches, cell biology as well as structural biology including X-ray crystallography and cryo-electron microscopy. The obtained results will have important impact on plant, animal and human health, as well as in industrial applications involving biological molecules.
Significance for science
Studies of molecular interactions of crucial protein virulence factors follow the research priorities of Horizon Europe themes and that of the National Research Program (Health and Life Sciences). The main focus of the proposed research programme is understanding of molecular and mechanistic details of protein virulence factors. We expect that the out coming results of this proposal will be important for the development of science in the following areas: 1. The study of the superfamilies of MACPF/CDC, actinoporin-like proteins and Nep1-like proteins will improve the understanding of the molecular mechanisms of some of the most pressing diseases of the modern world such as listeriosis, malaria and potato blight. Improved understanding of the molecular events underlying pathogenic effects will enable more rational design of intervention strategies. 2. Detailed understanding of the distribution of some of the actinoporin-like proteins will also allow an understanding of the role of the so-called small secreted proteins. Together with secondary metabolites, they are considered a goldmine for "omics" screening to discover effectors important for fungal or other organisms' survival and interactions with the environment. Understanding their distribution in nature will be crucial for understanding the various interactions of host organisms in the environment. 3. Through the innovative use of molecular biology approaches, such as ribosome display, coupled with other high-throughput approaches, such as next generation sequencing, we will better define binding regions for cell surface ligands for some of the virulence factors under investigation. We will employ integrative structural biology by combining different methodological approaches. This will also allow the selection of high-affinity binders for the regulation of biological activities of natural toxins. We plan to use smaller protein domains that prevent certain steps of pore formation and could therefore be useful both for the development of therapeutic applications and for functional studies aimed at understanding different aspects of protein-membrane interactions. 4. The identification of novel biological pores that can be used for the recognition of small molecules or large polymeric structures such as DNA or proteins have potential in various applications, from medicine and biotechnology to materials science or engineering. We expect our research to yield original results both at the level of basic science and in applications. Novel natural pores, their biochemical and biophysical properties as well as structures at the atomic level will give us insights into the mechanism of pore formation and thus into the biological role of these proteins, many of which are potent toxins. 5. We aim to elucidate the membrane damage mechanism induced by Nep1-like proteins. These proteins are present in many different pathogenic microorganisms and play a crucial role in pathogenesis. Our results will make an important contribution to the understanding of the interactions of Nep1-like proteins with the surface of plant cells, the mechanism of membrane damage and properties of pores and allow designing novel prevention strategies. 6. Insights into the protein interactions involved in potato virus Y will have an important impact in the field of virus-host or virus-vector interactions in general. The discovery of new candidate protein interactions within the PVY-host system will contribute to an improved understanding of the biological cycle of the virus within the plant, including entry and interactions with membranes, movement, and response to plant defence mechanisms. Moreover, it will importantly contribute to better insight in interactions between the viral proteins and the transmission vector, i.e. aphids.
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 Europe prioritizes research addressing infectious and chronic diseases of people, animals and plants. By research targeting the populations at risk, children, pregnant women and elderly, the programme 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. For these reasons, the proposal is very timely and relevant to Slovenian and European science with an aim of enhancing overall quality of life. The Department for Molecular Biology and Nanobiotechnology has long-standing fruitful collaborations (over 20 years) with the local pharmaceutical industry. Personnel trained in the department currently support several important aspects of production and development. Close contacts with domestic and foreign industry will be further developed by introducing and developing modern approaches to protein characterization within the Slovenian research infrastructure. We believe that this will make an important contribution to the future development of molecular pharmacology expertise among industrial partners and enable innovative solutions and personnel for new start-ups in Slovenia. We will further aim to promote expertise and infrastructure for studying molecular interactions and structures of biological molecules and complexes thus increasing scientific visibility of the programme group, NIC and Slovenian science as a whole. We have proven track record in establishing excellent facilities for structural biology by establishing the facility for cryo-electron microscopy and novel approaches in molecular interactions analysis, such as microscale thermophoresis and quartz crystal microbalance. We will aim to further integrate different expertise in Slovenia and, through participation in EU funded projects, also abroad. We are in perfect position to fill that void at the regional level, with our expertise in structural biology and molecular interactions. We are already in contact with other similar facilities in the Central Europe, which additionally keeps up up-to date with recent technological advances in the field. Our department provides an interdisciplinary environment that is ideal for the development of young scientists. Members of the programme group are involved in teaching in programmes at all levels at the University of Ljubljana. We have a long track record of successfully supervising PhD, MSc and BSc students. Successful links with the local pharmaceutical and biotechnology sector ensure that young researchers can continue their careers either in academia or industry after completing their PhD. In our department, we are aware that gender balance is crucial for the development of excellent science and a healthy society, allowing the realisation of ambitious ideas that are consistent with different views on life and science. The programme group will continue to promote and communicate science in the media. We have been involved in promoting science in daily newspapers, radio and TV, and science blogs, such as Kvarkadabra and Alternator, by writing short articles about the latest scientific achievements. Since the central idea of scientific work is the ultimate search for truth, promoting its principles among young people has an impact on the moral and cultural state of society. We will continue and expand our activities in the future by offering Mini Symposia and summer research camps for high school students. However, the main focus of the researchers in the programme group will be to continue publishing high-impact research results in major scientific journals, thus further promoting Slovenian science at home and abroad.
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