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Istraživačka grupa prof. Tanje Ćirković Veličković

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RAZVOJ I PRIMENA "OMICS" TEHNOLOGIJA I BIOLOŠKE MASENE SPEKTROMETRIJE
U OBLASTIMA HRANE, POŠOPRIVREDE I MEDICINE

Metodama "shotgun" proteomike i imunoproteomike se otkrivaju antigeni za dizajn vakcina za lečenje infekcija izazvanih intracelularnim bakterijama poput hlamidije, ali i za ispitivanje posttranslacionih modifikacija proteina i bolje razumevanje biologije ovih organizama i infekcija koje izazivaju [1]. Modifikacijama antigena može da se poboljša efikasnost i bezbednost vakcina. Novi proteinski terapeutici se testiraju in vitro i in vivo metodama [2, 3].

Posebno se proučava kako struktura i modifikacije proteina utiču na dinamiku degradacije proteina u endolizozomalnom odeljku a time i na tip imunog odgovora koji dati protein indukuje [4].

Modifikacije proteina izazvane obradom hrane mogu da utiču na procese digestije i preuzimanje proteina hrane u gastrointestinalnom sistemu, kao i na procese koje ovi proteini indukuju u ćelijama imunog sistema [5-7].

Metode protoemike i transkriptomike se kombinuju u cilju identifikacije i karakterizacije novih uzročnika alergija, unapređenja dijagnostike alergija i proizvodnje rekombinantnih alergena [8-10].

Metodama masene spektrometrije ispituje se polifenolni sastav različitih biljnih tkiva [11]. Mehanizam dejstva polifenola u imunomodulaciji se testira biohemijskim i metodama ćelijske biologije [12]. Metodama peptidomike se određuje struktura peptida nastalih dejstvom enzima digestivnog trakta [13, 14]. Nastali peptidi se izoluju u cilju karakterizacije biološke aktivnosti [15].

Interakcije biološki značajnih molekula hrane i proteina se proučavaju eksperimentalnim i teorijskim metodama. Određuje se afinitet vezivanja, tip interakcija uključenih u proces vezivanja, broj vezivnih mesta, efekti vezivanja na strukturu i stabilnost proteina i liganda [16-22].

Odabrane reference:
  1. Mihailovic J, Inic-Kanada A, Smiljanic K, Stein E, Barisani-Asenbauer T, Cirkovic Velickovic T: Lysine acetylation of major Chlamydia trachomatis antigens. EuPA Open Proteomics 2016, 10:63-69.
  2. Stanic-Vucinic D, Stojadinovic M, Mirkov I, Apostolovic D, Burazer L, Atanaskovic-Markovic M, Kataranovski M, Cirkovic Velickovic T: Hypoallergenic acid-sensitive modification preserves major mugwort allergen fold and delivers full repertoire of MHC class II-binding peptides during endolysosomal degradation. RSC Advances 2016, 6(91):88216-88228.
  3. Apostolovic D, Luykx D, Warmenhoven H, Verbart D, Stanic-Vucinic D, De Jong GAH, Velickovic TC, Koppelman SJ: Reduction and alkylation of peanut allergen isoforms Ara h 2 and Ara h 6; Characterization of intermediate- and end products. Biochimica et Biophysica Acta - Proteins and Proteomics 2013, 1834(12):2832-2842.
  4. Stojadinovic M, Pieters R, Smit J, Velickovic TC: Cross-linking of β-lactoglobulin enhances allergic sensitization through changes in cellular uptake and processing. Toxicological Sciences 2014, 140(1):224-235.
  5. Mihajlovic L, Radosavljevic J, Nordlund E, Krstic M, Bohn T, Smit J, Buchert J, Cirkovic Velickovic T: Peanut protein structure, polyphenol content and immune response to peanut proteins: In vivo are modulated by laccase. Food and Function 2016, 7(5):2357-2366.
  6. Radosavljevic J, Nordlund E, Mihajlovic L, Krstic M, Bohn T, Buchert J, Velickovic TC, Smit J: Sensitizing potential of enzymatically cross-linked peanut proteins in a mouse model of peanut allergy. Molecular Nutrition and Food Research 2014, 58(3):635-646.
  7. Perusko M, Al-Hanish A, Velickovic TC, Stanic-Vucinic D: Macromolecular crowding conditions enhance glycation and oxidation of whey proteins in ultrasound-induced Maillard reaction. Food Chemistry 2015, 177:248-257.
  8. Apostolovic D, Tran TAT, Hamsten C, Starkhammar M, Cirkovic Velickovic T, Van Hage M: Immunoproteomics of processed beef proteins reveal novel galactose-α-1,3-galactose-containing allergens. Allergy: European Journal of Allergy and Clinical Immunology 2014, 69(10):1308-1315.
  9. Smiljanic K, Apostolovic D, Trifunovic S, Ognjenovic J, Perusko M, Mihajlovic L, Burazer L, van Hage M, Cirkovic Velickovic T: Subpollen particles are rich carriers of major short ragweed allergens and NADH dehydrogenases: Quantitative proteomic and allergomic study. Clinical and Experimental Allergy 2017.
  10. Apostolovic D, Tran TAT, Ssnchez-Vidaurre S, Cirkovic Velickovic T, Starkhammar M, Hamsten C, Van Hage M: Red meat allergic patients have a selective IgE response to the α-Gal glycan. Allergy: European Journal of Allergy and Clinical Immunology 2015, 70(11):1497-1500.
  11. Mihajlovic L, Radosavljevic J, Burazer L, Smiljanic K, Cirkovic Velickovic T: Composition of polyphenol and polyamide compounds in common ragweed (Ambrosia artemisiifolia L.) pollen and sub-pollen particles. Phytochemistry 2015, 109:125-132.
  12. Krstic M, Stojadinovic M, Smiljanic K, Stanic-Vucinic D, Cirkovic Velickovic T: The anti-cancer activity of green tea, coffee and cocoa extracts on human cervical adenocarcinoma HeLa cells depends on both pro-oxidant and anti-proliferative activities of polyphenols. RSC Advances 2015, 5(5):3260-3268.
  13. Apostolovic D, Stanic-Vucinic D, De Jongh HHJ, De Jong GAH, Mihailovic J, Radosavljevic J, Radibratovic M, Nordlee JA, Baumert JL, Milcic M et al: Conformational stability of digestion-resistant peptides of peanut conglutins reveals the molecular basis of their allergenicity. Scientific Reports 2016, 6.
  14. Apostolovic D, Krstic M, Mihailovic J, Starkhammar M, Velickovic TC, Hamsten C, van Hage M: Peptidomics of an in vitro digested α-Gal carrying protein revealed IgE-reactive peptides. Scientific Reports 2017, 7.
  15. Minic SL, Stanic-Vucinic D, Mihailovic J, Krstic M, Nikolic MR, Cirkovic Velickovic T: Digestion by pepsin releases biologically active chromopeptides from C-phycocyanin, a blue-colored biliprotein of microalga Spirulina. Journal of Proteomics 2016, 147:132-139.
  16. Perusko M, Al-Hanish A, Mihailovic J, Minic S, Trifunovic S, Prodic I, Velickovic TC: Antioxidative capacity and binding affinity of the complex of green tea catechin and beta-lactoglobulin glycated by the Maillard reaction. Food Chemistry 2017, 232:744-752.
  17. Radibratovic M, Minic S, Stanic-Vucinic D, Nikolic M, Milcic M, Velickovic TC: Stabilization of human serum albumin by the binding of phycocyanobilin, a bioactive chromophore of blue-green alga spirulina: Molecular dynamics and experimental study. PLoS ONE 2016, 11(12).
  18. Al-Hanish A, Stanic-Vucinic D, Mihailovic J, Prodic I, Minic S, Stojadinovic M, Radibratovic M, Milcic M, Cirkovic Velickovic T: Noncovalent interactions of bovine α-lactalbumin with green tea polyphenol, epigalocatechin-3-gallate. Food Hydrocolloids 2016, 61:241-250.
  19. Vesic J, Stambolic I, Apostolovic D, Milcic M, Stanic-Vucinic D, Cirkovic Velickovic T: Complexes of green tea polyphenol, epigalocatechin-3-gallate, and 2S albumins of peanut. Food Chemistry 2015, 185:309-317.
  20. Minic SL, Milcic M, Stanic-Vucinic D, Radibratovic M, Sotiroudis TG, Nikolic MR, Velickovic TC: Phycocyanobilin, a bioactive tetrapyrrolic compound of blue-green alga Spirulina, binds with high affinity and competes with bilirubin for binding on human serum albumin. RSC Advances 2015, 5(76):61787-61798.
  21. Ognjenovic J, Stojadinovic M, Milcic M, Apostolovic D, Vesic J, Stambolic I, Atanaskovic-Markovic M, Simonovic M, Velickovic TC: Interactions of epigallo-catechin 3-gallate and ovalbumin, the major allergen of egg white. Food Chemistry 2014, 164:36-43.
  22. Stojadinovic M, Radosavljevic J, Ognjenovic J, Vesic J, Prodic I, Stanic-Vucinic D, Cirkovic Velickovic T: Binding affinity between dietary polyphenols and β-lactoglobulin negatively correlates with the protein susceptibility to digestion and total antioxidant activity of complexes formed. Food Chemistry 2013, 136(3-4):1263-1271.
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