Določanje tarčnih proteinov bioaktivnih komponent v hrani s protirakavim delovanjem z uporabo bioinformacijskih orodij.
Nutrigenomika proučuje vpliv hrane na genomsko stabilnost, epigenetske modifikacije, transkriptom, proteom, metabolom ter na razvoj kroničnih bolezni, kot je tudi rak. Namen naloge je bil pregled literature najbolje raziskanih bioaktivnih komponent v hrani s protirakavim delovanjem ter izbor spojine, kateri smo z uporabo bioinformacijskih orodij napovedali tarčne proteine pri človeku. Zasledili smo, da je epigalokatehin galat (EGCG) ena izmed najbolje raziskanih spojin v hrani, ki deluje proti raku. Eksperimentalno dokazano preprečuje mutacije DNA, saj sodeluje v DNA popravljalnih mehanizmih in preprečuje razvoj raka, saj je inhibitor proliferacije, angiogeneze, invazije in metastaziranja ter je induktor apoptoze. Z uporabo bioinformacijskega programa inverznega molekularnega sidranja Proteus smo napovedali 100 tarčnih proteinov pri človeku z najmanj proste vezne energije v interakciji z EGCG. 59 proteinskih tarč je program Proteus našel na novo in predstavljajo izhodišče za kasnejše eksperimentalne raziskave. S tem namenom smo opredelili vpliv tarčnih proteinov na transkripcijske dejavnike in njihove ciljne gene, analizirali vpliv na signalne transdukcijske poti ter s programom za vizualizacijo molekul PyMOL predstavili interakcije med EGCG ter nekaterimi tarčnimi proteini. Pripomogli smo k validaciji nutrigenomskih študij ter programa Proteus in k razvijanju nutrigenomske zbirke. V kombinaciji z individualnim predpisovanjem zdravil glede na posameznikov genotip, lahko razvijemo učinkovit sistem terapije proti raku.
Nutrigenomics studies the impact of nutrition on genomic stability, epigenetic modifications, transcriptome, proteome, metabolome and development of chronic diseases, such as cancer. The purpose of our master’s thesis is to review the literature of the best studied bioactive components in cancer prevention diet and to select the compound for which, using bioinformatics tools, target proteins were predicted. We observed that epigallocatechin gallate (EGCG) is one of the best studied compounds in the diet that works against cancer. It is experimentally proven that EGCG prevents DNA mutations, because it participates in DNA repair mechanisms and prevents development of cancer being an inhibitor of proliferation, angiogenesis, invasion and metastasizing and an inducer of apoptosis. By application of bioinformatics programme of Proteus inverse molecular docking we predicted 100 target proteins in humans with the least free binding energy in interaction with EGCG. 59 protein targets have been rediscovered by Proteus and they represent the starting point for subsequent experimental research. To this end, we determined the influence of target proteins on transcription factors and their target genes, and we analysed the effect on signal transduction pathways. By application of the PyMOL molecule visualisation programme we demonstrated the interactions between EGCG and certain target proteins. In this way we contributed not only to validation of nutrigenomic studies and the Proteus programme but also to the development of a nutrigenomic database. In combination with individual drug prescribing according to individual genotype, we can develop an effective anti-cancer treatment system.
2018
2018-11-25 07:45:33
1060
bioaktivne komponente, biotehnologija, epigenomika, hrana, komponente hrane, nutrigenomika, rak, transkriptomika
bioactive components, biotechnology, epigenomics, food, food components, nutrigenomics, cancer, transcriptomics
mb22
[S. Škufca]
Sandra
Škufca
70
Janez
Konc
991
Tanja
Kunej
994
UDK
4
606:616-006:591.133.1:575.112(043.2)
VisID
16
162594
COBISS_ID
3
9114233
4599.pdf
3206160
Predstavitvena datoteka
2018-11-25 07:45:40