NEW SYNERGISTIC STRATEGY TO TREAT CHRONIC WOUND INFECTIONS

Diabetes mellitus (DM) is one of the most prevalent chronic diseases worldwide, affecting 422 million people. It is estimated that the number of patients will double in the next 20 years. In 2015 in Serbia there were over 864.000 diagnosed DM patients and about 375.000 undiagnosed cases. Approximately 20–25% of DM patients will develop foot ulceration during the course of their disease. Up to a quarter of them will develop infections that will require amputation. Treatment of chronic wounds in DM patients has become extremely difficult due to infections caused by multidrug resistant organisms like antibiotic resistant Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus. Frequently, the cause of bacterial low sensitivity or resistance to antibiotics is their ability to form biofilms. Impaired healing in diabetic wounds is correlated with P. aeruginosa ability to form biofilms within the patients’ tissue(s).

The aim of this project is to discover novel drug leads for new antimicrobial agents targeting bacterial virulence and to develop new strategy for the efficient treatment of P. aeruginosa infections residing in chronic wounds including diabetic foot ulcers. The new drugs should exhibit anti-biofilm activity with low potential to develop resistance. Therefore, we will explore soil bacteria diversity for structurally new molecules and, based on structure-activity studies, derivatize selected anti-virulence drugs to improve their performance. The best candidate will be conjugated with novel two-component multifunctional nano-carriers to improve its therapeutic index and enable simultaneous bacterial biofilm disruption and clearance of deep tissue infection. This synergistic strategy is expected to provide effective therapy of difficult-to-treat chronic wound infections thus helping their timely healing.

Current projects

FUNDAMENTAL RESEARCH PROJECTS (2011–2017)
The role of transcription factors and small RNAs in abiotic stress in plants and genetic biodiversity of plant species in agriculture and biotechnology

Principal Investigator: Dr Vesna Maksimovic, IMGGE

OI 173005


Complex diseases as a model system for phenotype modulation – structural and functional analysis of molecular biomarkers

OI 173008

Principal Investigator: Dr Dragica Radojkovic, IMGGE 


Genes and molecular mechanisms promoting probiotic activity of lactic acid bacteria from Western Balkan

Principal Investigator: Dr Milan Kojic, IMGGE

OI 173019 


Microbial diversity study and characterization of beneficial environmental microorganisms

OI 173048

Principal Investigator: Dr Branka Vasiljevic, IMGGE 


Studying signal transduction pathways and epigenetic mechanisms that control human SOX genes expression: further insight into their roles in cell fate determination and differentiation

Principal Investigator: Dr Milena Stevanovic, IMGGE

OI 173051 


Molecular characterization of bacteria from genera Bacillus and Pseudomonas as potential agents for biological control

Principal Investigator: Prof. dr Djordje Fira, Faculty of Biology, University of Belgrade

Participants from IMGGE: Dr Milan Kojic and dr Sanja Mihajlovic

OI 173026 


Plant biodiversity of Serbia and the Balkans – assesment, sustainable use and protection

Principal Investigator: Prof. dr Dmitar Lakusic, Faculty of Biology, University of Belgrade

Participant from IMGGE: Dr Jelena Aleksic

OI 173030 


Cellular and molecular mechanisms of recovery of rats from experimental autoimmune encephalomyelitis

Principal Investigator: Dr Djordje Miljkovic, Institute for Biological Research "Sinisa Stankovic", University of Belgrade

Participant from IMGGE: Dr Gordana Timotijevic

OI 173035 


Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant in (bio)nanotechnology

Principal Investigator: Prof. dr Ivan Juranic, Faculty of Chemistry, University of Belgrade

Participant from IMGGE: Dr Djordje Francuski

OI 172035 


Combinatorial libraries of heterogeneous catalysts, natural products, modified natural products and their analogues: the way to new biologically active agents

Principal Investigator: Prof. dr Niko Radulovic, Faculty of Sciences and Mathematics, University of Nis

Participant from IMGGE: Dr Tatjana Ilic-Tomic

OI 172061 

III 41004

Principal Investigator: Dr Sonja Pavlovic, IMGGE 


Role of preoperative disease staging, prognostic, therapy markers, objectification of functional results in decision on rectal cancer treatment strategy, with the aim of improving oncology results and quality of life

Principal Investigator: Prof. Zoran Krivokapic, Faculty of Medicine, University of Belgrade

Participant from IMGGE: Dr Aleksandra Nikolic

III 41033


Development of new encapsulation and enzyme technology to produce biocatalysts and biologically active food components in order to increase its competitiveness, quality and safety

Principal Investigator: Prof. dr Branko Bugarski, Faculty of Technology and Metallurgy, University of Belgrade

Participants from IMGGE: Prof. dr Ljubisa Topisirovic and dr Ivana Strahinic

III 46010


Ethnogenesis of the Serbs during the Middle Ages (until c.1250): a comparative analysis of the historic-cultural heritage, genetic material and artefacts of material culture from the aspect of analytical chemistry

Principal Investigator: Dr Irena Cvijanovic, The Institute of History Belgrade

Participants from IMGGE: Dr Natasa Kovacevic-Grujicic, dr Milena Stevanovic, dr Marija Mojsin, dr Andrijana Klajn, dr Jelena Popovic, Slobodan Davidovic and Vladanka Topalovićc

III 47025 

INNOVATION PROJECTS
 

Development of technological processes for production of innovative probiotic products for prevention and treatment of intestinal infections in animals

Principal Investigator: Dr Natasa Golic, IMGGE

Project 2616 of the Innovation Fund


Development of innovative probiotic fermented product based on natural isolates of lactic acid bacteria for the treatment of dogs and cats suffering from diabetes

Principal Investigator: Dr Maja Tolinacki, IMGGE

Innovation project of the Ministry for Education, Science and Technological Development 

INTERNATIONAL PROJECTS
Dss1’s roles in genome integrity and protein oxidative damage control

International Centre for Genetic Engineering and Biotechnology (ICGEB), CRP/YUG14-01, 2015-2017

Principal Investigator: Dr Milorad Kojic, IMGGE


Survey for antimicrobials effective against carbapenem-resistant Gram-negative bacteria

International Centre for Genetic Engineering and Biotechnology (ICGEB), CRP/SRB15-02, 2016-2018

Principal Investigator: Dr Branko Jovcic, Faculty of Biology, University of Belgrade 


New synergistic strategy to treat chronic wound infections

Principal Investigator: Dr Lidija Senerovic, IMGGE
International Centre for Genetic Engineering and Biotechnology (ICGEB), CRP/SRB16-02, 2017-2019

BILATERAL PROJECTS
Functional characterization of striated muscle signaling protein Ankrd2 in aves

Research project within scientific and technological cooperation between Republic of Serbia and People's Republic of China, 2015-2017

Principal Investigator: Dr Snezana Kojic, IMGGE


The role of prothrombin in colon cancer

Research project within scientific and technological cooperation between Republic of Serbia and Republic of Croatia, 2016-2017

Principal Investigator: Dr Valentina Djordjevic, MGGE


Mining microbial resources for novel antifungal drug leads

Research project within scientific and technological cooperation between Republic of Serbia and Federal Republic of Germany

Principal Investigator: Dr Jasmina Nikodinovic-Runic, IMGGE

 

OTHER PROJECTS
 

Comparative studies on the in vitro neural differentiation of embryonic stem and embryonic carcinoma cells using expression profiling and cell interaction analysis

EVB. F23, Serbian Academy of Sciences and Arts, 2010-

Principal Investigator: Prof. dr Ljubisa Rakic, Serbian Academy of Sciences and Arts


Optimization (individualization) of the rectal cancer treatment using predictive molecular genetic biomarkers

F-20, Serbian Academy of Sciences and Arts, 2013-

Principal Investigator: Prof. dr Zoran Krivokapić, Faculty of Medicine, University of Belgrade

Participants from IMGGE: Dr Dragica Radojkovic and dr Aleksandra Nikolic


Functionalisation of bacterial polymers

BP2013, Bioplastech Ltd., Dublin, Ireland, 2013-

Principal Investigator: Dr Jasmina Nikodinovic-Runic, IMGGE


Unrevealing the taxonomic status of Fagus moesiaca in Serbia

National project of the Forestry Directorate of the Republic of Serbia, 401-00-1846/2016-10, 2016-2017

Principal Investigator: Prof. dr Mirjana Sijacic-Nikolic, Faculty of Forestry, University of Belgrade

Participant from IMGGE: Dr Jelena Aleksic

 

COST ACTIONS
Cooperation Studies on Inherited Susceptibility to Colorectal Cancer

BM1206, 2013-2017 


Networking towards clinical application of antisense-mediated exon skipping

BM1207, 2103-2017 


Systems Biocatalysis

CM1303, 2013-2017 


Gene regulation ensemble effort for the knowledge commons

CA15205, 2016-2020 


Diagnosis, monitoring and prevention of exposure-related noncommunicable diseases (DiMoPEx)

CA15129, 2016-2020 


Open Multiscale Systems Medicine (OpenMultiMed)

CA15120, 2016-2020

Optimization (individualization) of rectal cancer treatment using molecular and genetic predictive markers

Principal Investigator: Prof. dr Zoran Krivokapic, Faculty of Medicine, University of Belgrade

            The project aims to investigate prognostic and predictive molecular markers that could improve (individualize) treatment of rectal cancer. Treatment of this disease is still dominantly surgical. On the other hand surgery reached its current maximum in terms of local control. Further improvement in the treatment could be achieved using adjuvant and neoadjuvant therapy; better selection of patients for this treatment modality could be achieved using novel molecular markers.

Rational design and synthesis of biologically active and coordination compounds relevant for (bio)nanotechnology

Principal Investigator: Prof. dr Ivan Juranic 

            In this theoretical project we are looking deeper into how differences in electron properties of elements are directing their non-covalent interactions as well as how they influence the whole molecule by spreading their properties through chemical bonds. How do they influence the non-covalent interactions is answered by the studies of chemical bonding and electron properties of elements and molecules which we conduct using specialized software on high resolution X-Ray data.