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INSTITUTE OF MOLECULAR GENETICS
AND GENETIC ENGINEERING
University of Belgrade

IMGGE work program for 2022

Ministry of Education, Science and Technological Development of the Republic of Serbia
451-03-68/2022-14/200042

In 2022, research within IMGGE will be continued in the direction of: Research in the field of HUMAN MOLECULAR GENETICS will be focused on studying molecular markers significant for the diagnosis and treatment of selected rare diseases (metabolic diseases, Fabry disease, transthyretin amyloidosis). Innovative therapeutics will be tested on cellular model systems for rare diseases glycogenosis and primary ciliary dyskinesia (created by CRISPR / Cas technology). In the field of malignancy research, biobanks of ctDNA and regulatory RNA will be formed from liquid biopsies of patients with non-microcellular lung and pancreatic cancers. Associative studies will identify new biomarkers. The same approach will be used to assess placental function in pregnant women. New generation sequencing and artificial intelligence methods, machine learning at the IMGGE Center for Genome Sequencing and Bioinformatics will be used in pharmacogenomic and pharmacotranscriptomic studies to monitor response to therapy in leukemia and Crohn's disease and design predictive testing panels. A GWAS study of the association of genomic markers and the course of COVID-19 disease will be conducted. Research aimed at illuminating the molecular basis of complex diseases will continue. In the field of molecular pathophysiology of tumors, research will be focused on the characterization of potential therapeutic targets and diagnostic markers of colorectal cancer, lung cancer and rhabdomyosarcoma. The role of genetic and epigenetic factors on malignant cell processes will be examined. The mechanisms of resistance of tumor cells to chemotherapeutics will be studied, and the antitumor potential of selected compounds will be additionally tested. Tests of selected molecules that participate in the process of inflammation and response to oxidative stress will continue. These studies will monitor the effects that bacteria can have on chronic lung diseases, as well as the impact of electronic cigarettes on the development of lung diseases. The study of the etiopathology of cardiovascular diseases will continue with the study of genetic risk factors for their occurrence, as well as factors important for the effects of pharmacotherapeutic. In the field of regenerative biology, the process of skeletal muscle repair on the zebra model system and the mechanisms of action of selected proteins on tissue regeneration will be studied. The role of the SOX gene in the maintenance of nerve tissue homeostasis as well as in the induction of neural differentiation of pluripotent cells after stress induced by ischemia and reperfusion on in vitro model systems will be studied. Xenografts obtained by transplanting human tumor cells into zebrafish will be used as a platform to examine the assessment of tumor mass growth and metastatic spread as well as to examine responses to potential antitumor therapeutics. The achieved results will contribute to the identification of individual SOX genes as biomarkers of cellular stress and different types of tumors. The potential neurotoxic effects of the simultaneous consumption of energy drinks and alcohol will be analyzed in in vitro models of human neurogenesis systems. The detected biological activity of the tested compounds will be applied for the development of new therapeutic strategies. Research in the field of MOLECULAR MICROBIOLOGY, BIOTECHNOLOGY AND ECOLOGY OF MICROORGANISMS is based on the unique collections of microorganisms that IMGGE possesses. Part of this collection will be the basis for research in sociomicrobiology. Research will include the study of host-pathogen interactions, as well as small molecules and enzymes that modulate microbiological communication and virulence and inhibit bacterial, fungal, and mixed biofilms. New functionalized materials with antibiofilm activities will also be tested. In the field of pathogen epidemiology and molecular mechanisms of antibiotic resistance based on the "One Health" principle, research will be performed on samples of clinical origin, from animals as well as from the environment. In order to solve the problem of treating infections caused by multiple resistant pathogens (MRP), new antimicrobial molecules will be isolated and characterized, which will be tested in vitro and in vivo. Selected molecules will be further analyzed as potential therapeutics / alternatives to antibiotics. Work will also be done on the isolation and characterization of new lytic bacteriophages active against MRP, on the sequencing of their genomes as well as the genomes of bacteriophages ISTD by the RNA sequencing approach from phage-infected host cells. Research related to the characterization of the antimicrobial activity of Brevibacilllus and its application in agriculture in the control of fungal and bacterial infections will continue. The area of research that includes the interaction of probiotics and microbiota with the host will be focused on: the relationship between microbiota composition and the effectiveness of immunotherapy, examining the role of microbiota in neurodevelopmental and autoimmune diseases and the aging process, molecular characterization of probiotic potential of LAB and application of probiotics in lung diseases, study of the role of exopolysaccharides as postbiotics in prevention and mitigation of toxicity caused by heavy metals, the role of microbiota and probiotics in stimulating the growth of farmed fish and the role of the microbiota of flour and sourdough on the bio- and techno-functionality of bread and on the effects of bread on the intestinal cell model. The collection of microorganisms will be enriched with newly isolated microorganisms from polluted habitats, landfills and plastic waste collected from rivers. Selected microorganisms will be sequenced with the purpose of identifying new enzymes and biosynthetic pathways and will be a source of enzymes for the degradation and recycling of plastic waste into value-added molecules and materials. Work will be done on the development and optimization of eco-sustainable bioprocesses for the conversion of various waste materials into bacterial bioplastics, nanocellulose, biopigments and other valuable bioactive molecules, including antibiotics, antifungals and antitumor compounds. Bioactive molecules produced in fermentation processes will be characterized in detail and used as a basis for further structural optimizations aimed at improving their activity. In the field of MOLECULAR BIOLOGY OF PLANTS, it will be worked on the mechanisms of plant response to stress and mechanisms involved in maintaining the stability of the genome. Sequencing of the genome of Arabidopsis mutants is planned, as well as the generation of Arabidopsis lines that more strongly express the genes involved in the response and resistance to oxidative stress. Interactions between plants, beneficial bacteria and viruses will also be studied via an integrative "omix" approach, which will provide the knowledge necessary for application in agriculture. Molecular characterization of new cellular factors involved in the modulation of homologous recombination will continue. Transcriptome analysis will identify and analyze new cellular factors involved in both the recycling of oxidatively damaged molecules and the preservation of genome integrity. In the next year, special attention will be paid to the assessment, conservation and sustainable use of genetic resources and biodiversity of indigenous, rare and endangered plant and animal species, as well as species that are of special importance for agriculture. The results obtained in the field research combined with the application of the most modern molecular techniques will contribute to the qualitative improvement of activities in the fields of conservation, breeding and agricultural production, as well as environmental protection. The most significant progress in research at IMGGE was made possible by the opening of the Center for Genome Sequencing and Bioinformatics, which significantly expanded the capacity to apply the methods of NEW GENERATION SEQUENCING and BIOINFORMATIC ANALYSIS OF RESULTS that will be available to researchers from 2022. Thanks to these technologies, within the Unit for Work on Infectious Agents, the continuous monitoring of the SARS-CoV2 virus genome and the appearance of new mutations from January 2022 will be enabled, and non-invasive testing of prenatal blood samples within the NIFTY Unit will begin in March 2022.

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