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Research Group 2 - RG2 - Marija Gavrović-Jankulović

Main area of interest:
Ongoing projects:
Research description:

The specific, site-directed and efficacious delivery of drugs, particularly peptides, proteins or other macromolecules to different compartments of the gastrointestinal tract through the oral route is a major challenge in pharmaceutical science.
Lectins are a heterogeneous group of proteins and glycoproteins which bind carbohydrates specifically and with high affinity. Lectins can mediate mucoadhesion, cytoadhesion and cytoinvasion of drugs. Because of their specific carbohydrate binding, lectins can interact with the glycoconjugates present on the cell surfaces of the GIT. Among reagents available to direct vaccines or drugs specifically to the gut epithelium, plant lectins are prime candidates due to their stability in low pH conditions and their ability to bind specifically to epithelial cells.
The banana lectin (BanLec), a member of the jacalin-related family of lectins and belongs to the glucose/mannose. Current research is focused on the investigation of rBanLec interactions with glycostuctures of mucosal surface of the mouse digestive tract.

Diagnostic tests for food allergy frequently have poor specificity and sensitivity, as the quality of allergen extracts from fruits and other plant foods can vary due to the inherent presence of proteolytic enzymes, the ripening stage and/or storage conditions of the allergenic source materials. A prerequisite for the improvement of predictive and prognostic values of in vitro diagnostic results in food allergy is the development of reliable allergen reagents. Kiwifruit (Actinidia deliciosa) has been recognized as a food allergen source for almost 30 years. Since early 1960s, when kiwifruit became available, its growing popularity has been accompanied with an increasing number of reports of allergic reactions to kiwifruit. In the focus of our work is evaluation of allergenic potential of natural kiwifruit allergens. In addition the recombinant DNA technology has been employed for the production of selected kiwifruit allergens. Various biochemical and immunochemical methods are employed for validation of recombinantly produced proteins.

Strains of lactic acid bacteria (LAB) are commonly used in fermentation processes, in food preservation and in dried form as probiotic pills for human and animal consumption. Bacteriocins are antimicrobial peptides synthesized by ribosomes of bacteria which have the property of inhibiting other bacteria.
Besides their application in the food industry and their relevance in the improvement of food quality and safety, the increased interest in bacteriocinogenic LAB strains has been ascribed to their potential to modulate the immune system. LAB bacteriocins immunomodulatory properties are under investigation.

One of research group recently demonstrated that the interior of red blood cells (RBCs) of healthy individuals may contain significant but variable amounts of cholesterol associated with phospholipids that is firmly bound to haemoglobin (Hb) yielding an Hb-lipid adduct (Hb-Ch) [0.2–52% of total Hb]. The levels of Hb-Ch were significantly higher in winter than in summer and correlated positively with the plasma high density lipoprotein (HDL) cholesterol, suggesting a direct influence of plasma lipoprotein metabolism on the formation of Hb-Ch. It was documented that consumption of dietary lipids, including saturated fat and cholesterol, has an important influence on the level of Hb-Ch in RBCs. The low levels of Hb-Ch (15% of total Hb) were found in the group of low-fat intake subjects compared with high-fat intake subjects (30% of total Hb). A high-lipid diet increased Hb-Ch (by approximately 50%) in subjects with low Hb-Ch at onset, whereas a low-lipid diet decreased Hb-Ch (by approximately 40%) in subjects with high Hb-Ch at onset [2]. Efflux of cholesterol and phospholipids from Hb-Ch to fasting plasma HDL fraction in vitro was demonstrated [3]. Epidemiological data consistently show that populations with high-fat diets have increased incidence of coronary heart disease. Our results indicate that typical Western-style diets, rich in saturated fat and cholesterol and relatively low in polyunsaturated fat and dietary fibre, are associated with the accumulation of cholesterol in the interior of erythrocytes. Therefore, Hb-Ch was postulated to represent a new form of cholesterol in circulation that contributes to the permanent removal of excess of (potentially detrimental) non-esterified cholesterol from the circulation. In this way, RBCs may form part of the complex (anti-atherogenic) mechanisms involved in the first line "defence" against an excess of free cholesterol in circulation, most probably of dietary origin. Current research focus is to decipher the contribution of individual lipids (e.g. saturated fat or cholesterol) on the Hb-Ch level, by employing more strictly controlled dietary studies in order to delve deeper into our observed phenomena.

Group members and ongoing projects:

dr Rajna Dimitrijević, senior researcher

dr Milan Nikolić, senior researcher

Milica Popović, PhD student

Milica Grozdanović, PhD student

Milena Spasić, PhD student

Mohamed Salem Alzwam Abugren, PhD student

Selected recent publications:
  1. Marija Gavrović-Jankulović, Rajna Dimitrijević, Marijana Stojanović: Banana Lectin Interactions with the Immune System: Implications for Future Therapeutic Applications. In: Bananas: Nutrition, Diseases and Trade Issues. Editor: Alisha E. Cohen. ISBN 978-1-61761-124-7 in press.
  2. Burazer L, Milovanović K, Milovanović M, Vučković O, Veličković TC, Gavrović-Jankulović M. Impact of Dermatophagoides pteronyssinus mite body raw material on house dust mite allergy diagnosis in a Serbian population. Med Vet Entomol. 2010 in press.
  3. Marija Gavrović-Jankulović, Milica Grozdanović. Application of plant-derived food lectins in proteoglycomics and immunomodulation. In: Handbook of Nutritional Biochemistry: Genomics, Metabolomics and Food Suply. Editors: S. Haugen, S. Meijer. ISBN: 978-1-60741-916-7.
  4. Rajna Dimitrijević, Milka Jadranin, Lidija Burazer, Sanja Ostojić, Marija Gavrović-Jankulović. Evaluation of the thermal stability and digestibility of heterologously produced banana lectin. Food Chemistry 2010; 120:1113-1118.
  5. Popović MM, Milovanović M, Burazer L, Vučković O, Hoffmann-Sommergruber K, Knulst AC, Lindner B, Petersen A, Jankov R, Gavrović-Jankulović M. Cysteine proteinase inhibitor Act d 4 is a functional allergen contributing to the clinical symptoms of kiwifruit allergy. Mol Nutr Food Res. 2010; 54(3):373-80.
  6. Stojanović MM, Zivković IP, Petrusić VZ, Kosec DJ, Dimitrijević RD, Jankov RM, Dimitrijević LA, Gavrović-Jankulović MD. In vitro stimulation of Balb/c and C57 BL/6 splenocytes by a recombinantly produced banana lectin isoform results in both a proliferation of T cells and an increased secretion of interferon-gamma. Int Immunopharmacol. 2010 Jan;10(1):120-9.
  7. Dimitrijević R, Stojanović M, Zivković I, Petersen A, Jankov RM, Dimitrijević L, Gavrović-Jankulović M. The identification of a low molecular mass bacteriocin, rhamnosin A, produced by Lactobacillus rhamnosus strain 68. J Appl Microbiol. 2009;107(6):2108-15.
  8. Nikolić M., Stanić D., Antonijević N., Niketić V. Cholesterol bound to hemoglobin in normal human erythrocytes: a new form of cholesterol in circulation? Clin. Biochem. 2004;37:22-26.
  9. Nikolić M., Ristić Medić D., Stanić D., Poštić M., Arsić A., Niketić V. Dietary lipid intake influences the level of cholesterol bound to haemoglobin in human erythrocytes, Eur. J. Nutr. 2008;47:123-130.
  10. Nikolić M., Stanić D., Baričević I., Jones D.R., Nedić O., Niketić V. Efflux of cholesterol and phospholipids derived from the haemoglobin-lipid adduct in human red blood cells into plasma, Clin. Biochem. 2007;40:305-309.
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