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Projects / Programmes source: ARIS

Systemic determination of legumain physiological roles

Research activity

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

Code Science Field
1.06  Natural Sciences  Biological sciences 
Keywords
legumain, proteolysis, degradomics, proteomics, transcriptomics, systems biology
Evaluation (rules)
source: COBISS
Points
4,895.6
A''
1,445.9
A'
2,871.8
A1/2
3,406.69
CI10
27,027
CImax
4,318
h10
58
A1
18.18
A3
6.07
Data for the last 5 years (citations for the last 10 years) on July 26, 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  408  32,567  29,821  73.09 
Scopus  423  35,593  32,703  77.31 
Researchers (12)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  19116  PhD Špela Baebler  Biotechnology  Researcher  2021 - 2024  319 
2.  18801  PhD Marko Fonović  Biochemistry and molecular biology  Head  2021 - 2024  189 
3.  38199  PhD Marija Grozdanić  Biochemistry and molecular biology  Junior researcher  2021 - 2024  13 
4.  12688  PhD Kristina Gruden  Biotechnology  Researcher  2021 - 2024  993 
5.  37409  PhD Maja Križnik  Biotechnology  Researcher  2021 - 2024  43 
6.  53968  Nastja Marondini  Biotechnology  Researcher  2021 - 2024  11 
7.  37797  PhD Georgy Mikhaylov  Biochemistry and molecular biology  Researcher  2021 - 2024  54 
8.  29617  PhD Marko Petek  Biotechnology  Researcher  2021 - 2024  174 
9.  34502  PhD Živa Ramšak  Biology  Researcher  2021 - 2024  121 
10.  52063  Tilen Sever  Biochemistry and molecular biology  Junior researcher  2021 - 2022  16 
11.  07561  PhD Boris Turk  Biochemistry and molecular biology  Researcher  2021 - 2024  1,038 
12.  33762  PhD Robert Vidmar  Biochemistry and molecular biology  Researcher  2021 - 2024  149 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0106  Jožef Stefan Institute  Ljubljana  5051606000  92,024 
2.  0105  National Institute of Biology  Ljubljana  5055784  13,485 
Abstract
Legumain is an evolutionary conserved cysteine protease with narrow substrate specificity. It is ubiquitously expressed in various cell and tissue types of animals, plants and other eukaryotes. Although it is primarily located in the endo/lysosomal compartments, legumain can be translocated to the cytosol, nucleus and extracellular space. In the last decade, numerous studies have connected legumain activity with several clinically relevant pathological processes such as cancer, neurodegeneration, atherosclerosis and acute cardiovascular events. However, only a handful of legumain physiological substrates has been identified so far and the exact mechanisms through which legumain influences biological processes remain largely unknown. In the course of our preliminary work using COFRADIC degradomic methodology, we were able to identify the largest set of legumain substrates reported to date and this finding puts us in a unique position to determine the pathways through which legumain affects physiology of cells and tissues on molecular level. Interestingly, majority of our identified legumain substrates are cytoplasmic proteins involved in regulation of gene transcription, RNA stability and intracellular signalling. Our finding therefore indicates the presence of completely novel legumain functions. The aim of the proposed work is to append the legumain substrate data with blood plasma peptidomic approach and to determine how proteolytic cleavage of legumain substrates influences processes like RNA metabolism and cellular signalling. To reveal that, we will perform a complex combination of proteomic, degradomic, phosphoproteomic and transcriptomic analysis of WT and leg-/- mice tissue samples. Obtained data will be bioinformatically integrated which will help us connect most relevant cleaved substrates with affected downstream processes and pathways. In the final stage, we will also develop cell-based assays, which will validate cleavages of selected substrates with specific cellular processes. We are convinced that such comprehensive analysis preformed in in vivo experimental setting will provide an unprecedented new insight into legumain biological function. This knowledge will also be able to expand the use of legumain targeting in clinical applications such as development of novel diagnostic, prognostic and therapeutic approaches.
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