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Projects / Programmes source: ARIS

Molecular mechanisms of regulation of cellular processes related to some human diseaes

Periods
Research activity

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

Code Science Field
P4   Natural sciences and mathematics  P4  

Code Science Field
3.01  Medical and Health Sciences  Basic medicine 
Keywords
Signal transduction, enzymes, gene expression, gene polymorphysm, drug delivery vectors, cell cultures, eukaryotic microorganisms, stressors, steroids, recombinant proteins
Evaluation (rules)
source: COBISS
Researchers (44)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  28352  PhD Jure Aćimović  Neurobiology  Researcher  2009 - 2013  99 
2.  29474  PhD Maja Anko  Biochemistry and molecular biology  Researcher  2009 - 2013  38 
3.  16130  PhD Aljoša Bavec  Neurobiology  Researcher  2009 - 2013  130 
4.  31946  PhD Nataša Beranič  Biochemistry and molecular biology  Junior researcher  2009 - 2013  30 
5.  25438  PhD Petra Bohanec Grabar  Metabolic and hormonal disorders  Junior researcher  2009  35 
6.  27575  PhD Petra Brožič  Biochemistry and molecular biology  Researcher  2009 - 2011  51 
7.  28343  PhD Mojca Brunskole Švegelj  Biochemistry and molecular biology  Researcher  2009 - 2012  31 
8.  36374  PhD Jerneja Čremožnik Zupančič  Microbiology and immunology  Junior researcher  2013  67 
9.  08777  PhD Bronislava Črešnar  Biochemistry and molecular biology  Researcher  2009 - 2013  98 
10.  11711  PhD Vita Dolžan  Biochemistry and molecular biology  Researcher  2009 - 2013  765 
11.  26236  David Fatur    Technical associate  2009 - 2013 
12.  29348  PhD Martin Fettich  Biochemistry and molecular biology  Junior researcher  2009 - 2011  11 
13.  19129  PhD Marko Goličnik  Neurobiology  Researcher  2009 - 2013  144 
14.  33110  PhD Katja Goričar  Oncology  Junior researcher  2010 - 2013  287 
15.  05935  PhD Nina Gunde-Cimerman  Biotechnology  Researcher  2009 - 2013  1,258 
16.  29240  PhD Neli Hevir  Pharmacy  Researcher  2009 - 2013  62 
17.  34327  PhD Sašo Jančič  Biotechnology  Junior researcher  2011 - 2013  20 
18.  35356  PhD Barbara Jenko Bizjan  Medical sciences  Junior researcher  2012 - 2013  73 
19.  28395  PhD Matej Kastelic  Psychiatry  Researcher  2009 - 2013  35 
20.  34355  PhD Anja Kejžar  Natural sciences and mathematics  Junior researcher  2011 - 2013  20 
21.  17883  Nevenka Klenovšek Špat    Technical associate  2009 - 2013 
22.  31947  PhD Tilen Konte  Biochemistry and molecular biology  Researcher  2009 - 2013  33 
23.  30749  PhD Anja Korenčič  Biology  Junior researcher  2012  49 
24.  24392  PhD Katja Kristan  Pharmacy  Researcher  2009 - 2013  95 
25.  18847  Marjan Kužnik    Technical associate  2009 - 2010 
26.  11699  PhD Tea Lanišnik Rižner  Metabolic and hormonal disorders  Researcher  2009 - 2013  574 
27.  02934  PhD Helena Lenasi  Biochemistry and molecular biology  Researcher  2009 - 2013  78 
28.  24288  PhD Metka Lenassi  Natural sciences and mathematics  Researcher  2009 - 2013  201 
29.  17884  Klavdija Makovec    Technical associate  2009 - 2013 
30.  07085  PhD Tomaž Makovec  Biochemistry and molecular biology  Researcher  2013  48 
31.  18845  Milena Marušič    Technical associate  2009 - 2013 
32.  28887  Špela Petrič    Technical associate  2009 - 2011  28 
33.  06777  PhD Ana Plemenitaš  Biochemistry and molecular biology  Researcher  2009 - 2013  379 
34.  34259  PhD Maša Sinreih  Biochemistry and molecular biology  Junior researcher  2011 - 2013  87 
35.  07086  Savica Soldat    Technical associate  2009 - 2013 
36.  03723  PhD Jurij Stojan  Neurobiology  Head  2009 - 2013  261 
37.  25593  PhD Tina Šmuc  Metabolic and hormonal disorders  Researcher  2009 - 2013  57 
38.  34402  PhD Nuša Trošt  Human reproduction  Junior researcher  2011 - 2013  10 
39.  18510  PhD Martina Turk  Biochemistry and molecular biology  Researcher  2009 - 2013  190 
40.  16114  PhD Katja Vouk  Biochemistry and molecular biology  Researcher  2009 - 2013  80 
41.  32061  PhD Janja Zajc  Plant production  Junior researcher  2009 - 2013  163 
42.  16103  PhD Polona Zalar  Microbiology and immunology  Researcher  2009 - 2013  462 
43.  04350  PhD Matjaž Zorko  Neurobiology  Researcher  2009 - 2013  190 
44.  03082  PhD Marija Žakelj-Mavrič  Biochemistry and molecular biology  Researcher  2009 - 2013  117 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  48,188 
2.  0481  University of Ljubljana, Biotechnical Faculty  Ljubljana  1626914  66,240 
Abstract
In scope of our research program we study the mechanisms involved in regulation of cellular processes at the level of isolated, recombinant wild type and mutant enzymes, at the level of signal transduction, triggered by specific hormones or changes in salinity of the environment, and at the level of identification and expression of genes. Studies at the level of enzyme action include the following enzymes: cholinesterases that are involved in propagation of nerve signals across the synapses, enzymes belonging to the superfamily of SDR (short chain dehydrogenases/reductases) and cytochrome P450 hydroxylases involved in steroid metabolism as well as enzymes, involved in carbohydrate metabolism and metabolism of xenobiotics in mesophilic and halophilic model microorganisms. Signal transduction is studied on model systems and is aimed in hormone - receptor interactions, signal transduction via G-proteins and transfer of the signal via the MAP kinase cascade. In scope of hormone - receptor interaction, we study the effect of non-steroid compounds on fungal cytosolic progesterone receptor, as well as the coupling of fungal membrane-bound progesterone receptor, human angiotensin receptor and human glucagon like peptide-1 receptor to G-proteins. HOG signal transduction pathway, which is involved in osmosensing and play an important role in the adaptation to changes in environmental salinity, is studied as an example of MAP protein kinase signalling cascade. Extremely salt tolerant H.werneckii, isolated from the environments with high NaCl concentration, is used as the model organism. At the genomic level, genes expressed under general and specific stressors are studied. The dynamics of the fungus R. nigricans molecular response to general stressors - fungitoxic steroids (progesterone, testosterone and deoxycorticosterone) is analyzed at the level of gene expression of cytosolic subgroup of Hsp70 family, enzymes of hydroxylation system and carbohydrate metabolizing enzyme. Moreover, we attempt to identify additional genes, which are up- or downregulated during exposure of this fungus to different stressors. Expression profile of Hog1 kinase target genes gpd and ena will be analysed in halophilic model organisms. By using global approach, we will try to identify novel, yet unidentified genes which are potentially involved in the mechanism of adaptation to high salt concentration, both at the level of transcriptome and at the level of proteome. In the field of genetic polymorphisms of xenobiotic metabolising enzymes we are mostly interested in polymorphisms that could affect the metabolism of drugs with a narrow therapeutic window. Using genotyping approach we study the influence of genetic polymorphisms on the interindividual variability in drug metabolism, drug efficiency and adverse drug effects, with the aims for rational and individualised drug treatment. Genetic susceptibility to environmental carcinogenesis due to interindividual variability in xenobiotic metabolism will be studied by comparing the frequency distribution of polymorphic alleles between cancer patients and healthy controls. In design and development of peptide drug-delivery vectors, we are focused in sequence modulation of the cell-penetrating peptide transportan with the aim to minimize damaging effect of this peptide on the membrane in order to improve its internalisation properties. We will also try to design peptides with combined cell-penetrating ability and ability to activate G-proteins in order to modulate physiological processes in the selected organs "ex vivo" and in model organisms; we are particularly interested in vascular system and blood pressure regulation.
Significance for science
The results of our research group made a major impact in the fields of our interest: in the field of basic enzymology we developed new kinetic methods for the analysis of complex reaction mechanisms; our studies of signal pathways in cell systems and model organisms helped to improved the current understanding of signal transduction and adaptation to stress; while studies of molecular mechanisms in health and diseases lead to identification of new diagnostic and prognostic biomarkers and new targets for treatment. The important contribution of our research for science is evident from over 150 original scientific papers published in the evaluation period. More than two-thirds of these papers were rated as important achievements, one third as very important achievements. The impact of our publications on the respective research fileds is reflected in over 8000 citations and the originality and novelty of our research topics is reflected in 24 completed doctoral theses. Members of the program group presented over 50 lectures and 280 contributions at international meetings. They also help to shape their respective scientific fields by serving as editors and members of editorial boards of scientific journals. High potential for dissemination and translation of our novel findings into technological processes and clinical studies is reflected in several basic, applied and postdoctoral research projects of the group members. However, most of the clinical collaborations occurs outside formal research projects due to a limited set of research hours and is reflected only in joint publications and co-mentorship of doctoral theses.
Significance for the country
The fact that 7 researchers in the programme group are full professors, speaks for our outstanding achievements in terms of research excellence, and teaching and professional quality. We lectured several core and elective courses in the field of biochemistry and molecular biology at the undergraduate and post-graduate studies and mentored 19 PhD theses and comentored 6 PhD theses in the last 5 years. We also mentored 21 and comentored 18 graduation theses. Considering the fact that students at the Faculty of Medicine do not have graduation theses, these numbers show that we also actively participate in teaching at other faculties. Thus we significantly contribute to the quality of the undergraduate and graduate education at the University of Ljubljana, as well as to the development of the field of biochemistry and molecular biology in Slovenia. When taking into account our full-time teaching load, our programme group achieved outstanding results per FTE unit. In addition to the development of higher education, the research program had significant impact on the international recognition of Slovenia. As the studied halophilic organisms were first isolated in Sečovlje salterns, Slovenian researchers in this field achieved unprecedented international recognition, which is very important for the promotion of Slovenia. The first results of studies on the genome of these organisms were already published, but the emerging results may lead to new patent applications and may also have a great importance for the economy, because organisms with enhanced tolerance to salt are interesting for bioremediation, biotechnology and agronomy. Our research programme also had a big impact on health care. Translation of basic research to clinical applications constituted an important part of our programme. In the course of our clinical studies in the field of hormone-related disorders, cancer and rheumatoid arthritis, we have identified new potential diagnostic and prognostic markers, new targets for treatment as well as pharmacogenetic markers of response to treatment. When supported by replication and multicenter studies, our research may support the transition from the current treatments, based on the characteristics of the total patient population, to the predictive, preventive and personalized medicine. In addition to more effective treatment, which means big savings for health care system, also patients' quality of life of will significantly improve.
Most important scientific results Annual report 2009, 2010, 2011, 2012, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2009, 2010, 2011, 2012, final report, complete report on dLib.si
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