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Research Group 1 - RG1 - Tanja Cirkovic Velickovic

University of Belgrade, Faculty of Chemistry

Research description:
Beta-lactoglobulin (BLG) – 3D structure There is a lot of data on the linkage between the food digestion and human health. Hydrolysis of dietary proteins releases free amino acids and peptides resulting in a myriad of potential bioactivities such as antihypertensive, antimicrobial, immunomodulatory and appetite regulation properties. On the other hand, gut digestive system is a gate-keeper for food allergens, acting eather as a protective barrier by degrading food allergens thus preventing sensitization to digestion-labile allergens or by reducing the amount of a food allergen that can reach the digestive immune system in the elicitation phases of food allergy. The stability of protein sequences to digestion is considered to be a major factor in the sensitization of humans to dietary proteins leading to food allergy instead of inducing oral tolerance to abundant food proteins. Many of the food allergens sensitizing via the oral route are stable proteins that are very resistant to heat and digestion by gastrointestinal enzymes, or while digested give peptide fragments of significant size which retain their IgE binding and T cell stimulating capacities. New studies have also shown that readily digestible food allergens may sensitise and elicit reaction, probably because of aggregation of peptides.

Beside allergen structure, new data are emerging on the influence of various other factors on the allergen survival and uptake by the gut immune system, some of them related to the properties of the food matrix, and other to the way we process food.
Impairment of the digestion process by pepsin by elevation of the gastric pH, the therapeutic goal of anti-ulcer medication, has recently been linked to an increasing incidence of food allergies. Raised intragastric pH may be a contributory factor to allergenicity of food proteins in infants and older individuals who may have reduced gastric functioning.

Pepsin in action Beside structural stability of food proteins, others factors that are of influence on the food protein digestion are broad and those described so far include: food processing conditions (physical, chemical, enzymatic i.e. oxidases and transglutaminases), pepsin inhibition/activation by the food matrix components (plant hydrocolloids, polyphenols), effects of excipients and stabilizers (e.g surfactants, thickeners) on protein structure, effects of food supplements and medication, as well as increase in pH of the gastric fluid eather physiologically, by medication intake or by the buffering effect of food.

Links between food and human health are a top research priority for Europe. The built of knowledge on all those various and complex interactions between food components, digestive system and gut immune system can help us understand better immunopathologies, manufacture safer food and design improved protein therapeutics for oral intake.

The stability of protein sequences to digestion is considered to be a major factor in the sensitization of humans to dietary proteins leading to food allergy instead of inducing oral tolerance to abundant food proteins. Many of the food allergens sensitizing via the oral route are stable proteins that are very resistant to heat and digestion by gastrointestinal enzymes, or while digested give peptide fragments of significant size which retain their IgE binding and T cell stimulating capacities. New studies have also shown that readily digestible food allergens may sensitise and elicit reaction, probably because of aggregation of peptides.

Beside allergen structure, new data are emerging on the influence of various other factors on the allergen survival and uptake by the gut immune system, some of them related to the properties of the food matrix, and other to the way we process food.
Impairment of the digestion process by pepsin by elevation of the gastric pH, the therapeutic goal of anti-ulcer medication, has recently been linked to an increasing incidence of food allergies. Raised intragastric pH may be a contributory factor to allergenicity of food proteins in infants and older individuals who may have reduced gastric functioning.

Beside structural stability of food proteins, others factors that are of influence on the food protein digestion are broad and those described so far include: food processing conditions (physical, chemical, enzymatic i.e. oxidases and transglutaminases), pepsin inhibition/activation by the food matrix components (plant hydrocolloids, polyphenols), effects of excipients and stabilizers (e.g surfactants, thickeners) on protein structure, effects of food supplements and medication, as well as increase in pH of the gastric fluid eather physiologically, by medication intake or by the buffering effect of food.


Main areas of research of the group are:

Group members and ongoing projects:

TCV Group

Dragana Stanic, PhD, senior researcher
Projects: Physical, chemical and enzymatic modifications of proteins
Influence of new processing conditions on techno-funtional properties and biologial activity of food proteins
Development of new oral therapeutics of respiratory allergies to mugwort pollen

Natalija Milcic-Matic, PhD, part-time senior researcher
Projects: Major allergens of Ambrosia elatior in allergic dogs
Allergenicity of chemically and enzymatically modified allergens

Jelena Radosavljevic, PhD student
Projects: Allergenicity and sensitizing potential of bioprocessed milk and peanut proteins
Influence of gastric fluid acidity on digestion pattern of BLG in vitro and in vivo
Cloning and production of peanut allergens Ara h 2 and Ara h 6

Jana Ognjenovic, PhD student
Projects: Characterization of major linden pollen allergens
Creation of phage-display cDNA library of linden pollen

Luka Mihajlovic, PhD student
Projects: Structure and biological activity of polyphenolic compounds of pollens
Immunomodulatory and anti-allergic properties of food matrix

Marija Stojadinovic, PhD student
Projects: Influence of new food processing methods on structure and biological activity of BLG
In vitro bioavailability, in vivo transit and uptake of modified/processed whey proteins

Ivana Prodic, PhD student
Projects: Modifications of food proteins by high intensity ultrasonication

Danijela Apostolic, MS student
Projects:Influence of plant polyphenols on pepsinolysis and bioavailability of whey proteins

Ayah Musbah, MS student
Projects: In vitro bioavailability testing of micronutrients

Maja Krstic, MS student
Projects: Mechanism of cytotoxic activities of polyphenolic extracts of coffee, tea and cocoa

Jelena Vesic, MS student
Projects: Binding of catechins to major food allergens: binding affinities, docking analysis and relevance in prevention of IgE binding in vitro and in cellular assays


Research skills and methods applied by the group:
Selected recent publications:
  1. Stanic, Dragana; Radosavljevic, Jelena; Stojadinovic, Marija; Cirkovic Velickovic, Tanja. Application of Ion-exchanger in the Separation of Whey Proteins and Lactin from Milk Whey. In: Ion-exchange Technology II - Applicationss (2012), Springer, Inamuddin; Luqman, Mohammad (Eds.), ISBN 978-94-007-4025-9
  2. Stanic-Vucinic, Dragana; Cirkovic Velickovic, Tanja. Enzymatic and chemical modifications of food allergens. In: Allergic Diseases - highlights in the clinic, mechanisms and treatment (2012), InTech Open Access Publisher, Celso Pereira (Ed.), ISBN 978-953-307-986-8
  3. Tanja Cirkovic Velickovic, Jana Ognjenovic and Luka Mihajlovic. Separation of Amino Acids, Peptides and Proteins by Ion-Exchange Chromatography. In Ion-exchange Technology II- Applications (2012), Inamuddin; Luqman, Mohammad (Eds.), ISBN 978-94-007-4025-9
  4. M. Stojadinovic, L. Burazer, D. Ercili-Cura, A. Sancho, J. Buchert, T. C. Velickovic and D. Stanic-Vucinic (2012) One-step method for isolation and purification of native B-lactoglobulin from bovine whey. Journal of the Science of Food and Agriculture, in press
  5. Z. Tantoush, D. Stanic, M. Stojadinovic, J. Ognjenovic, L. Mihajlovic, M. Atanaskovic-Markovic and T. Cirkovic Velickovic (2011) Digestibility and allergenicity of B-lactoglobulin following laccase-mediated cross-linking in the presence of sour cherry phenolics. Food Chemistry 125 (1):84-91
  6. D. Stanic, E. Monogioudi, E. Dilek, J. Radosavljevic, M. Atanaskovic-Markovic, O. Vuckovic, L. Raija, M. Mattinen, J. Buchert and T. Cirkovic Velickovic (2010) Digestibility and allergenicity assessment of enzymatically crosslinked beta-casein. Mol Nutr Food Res 54 (9):1273-84. doi:10.1002/mnfr.200900184 [doi]
  7. N. Polovic, A. Obradovic, M. Spasic, B. Plecas-Solarovic, M. Gavrovic-Jankulovic and T. Cirkovic Velickovic (2010) In vivo digestion of a thaumatin-like kiwifruit protein in rats. Food Digestion 1 (1-2):5-13
  8. T. C. Velickovic, J. Radosavljevic and D. Stanic (2009) Digestibility of food allergens. CAB Reviews: Perspectives in Agriculture, Veterinary Science, Nutrition and Natural Resources 4 (6)
  9. D. Stanic, J. Radosavljevic, N. Polovic, M. Jadranin, M. Popovic, O. Vuckovic, L. Burazer, R. Jankov and T. C. Velickovic (2009) Removal of N-terminal peptides from beta-lactoglobulin by proteolytic contaminants in a commercial phenol oxidase preparation. International Dairy Journal 19 (12):746-52.
  10. I. Perovic, M. Milovanovic, D. Stanic, L. Burazer, D. Petrovic, N. Milcic-Matic, G. Gafvelink, M. van Hage, R. Jankov and T. C. Velickovic (2009) Allergenicity and immunogenicity of the major mugwort pollen allergen art v 1 chemically modified by acetylation. Clinical and Experimental Allergy 39 (3):435-46. doi:10.1111/j.1365-2222.2008.03158.x
  11. T. C. Velickovic, S. Thunberg, N. Polovic, T. Neimert-Andersson, H. Gronlund, M. van Hage and G. Gafvelin (2008) Low levels of endotoxin enhance allergen-stimulated proliferation and reduce the threshold for activation in human peripheral blood cells. International Archives of Allergy and Immunology 146 (1):1-10. doi:10.1159/000112497
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