imagine (Institute of molecular genetics and genetic engineering)
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High-performing structural optimization of graphene quantum dots as glyphosate herbicide photoluminescent probes: real case studies and mechanism insights
No full textThe widespread usage of the herbicide glyphosate calls for urgent action, aiming at the development of new, simple, low-cost, and eco-friendly detection approaches. In the last decade, investigation of graphene quantum dots (GQDs) as potential optical probes for various pollutants rapidly grew, thanks to their easy-manipulative structure, remarkable photoluminescence (PL) in the visible part of the spectrum, good dispersibility, biocompatibility, and non-toxicity, as well. Herein, a fast, simple, and environmentally friendly method for GQDs structural modification is presented. GQDs raw powder was exposed to γ- rays at three different doses (100, 200, and 300 kGy) in air, without any solvent or reagents. Irradiation of dots under such affordable conditions led to the additional incorporation of oxygen-containing moieties in the GQD structure. For the first time, oxygen-rich GQDs irradiated at a 300 kGy dose were successfully applied as direct turn-off PL probe for glyphosate detection. The high coefficient of determination (R-squared (R2) = 0.99) and very low limit of detection (3.02 μmol L-1) reveal good linearity between the potential sensor and analyte, as well as sensitivity. Glyphosate was successfully detected in celery samples, with a recovery value of 107 ± 0.85%. To evaluate the biological safety of the proposed sensing probe, [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) and the hemolysis assays were performed. Obtained results show that irradiated and non-irradiated GQDs did not cause the death of MRC-5 cells, and hemolysis of erythrocytes. The obtained results demonstrate that GQDs irradiated in an air medium can be potentially applied for glyphosate detection
Enhancing non-communicable disease research excellence through zebrafish capacity building (ZeNCure)
Get PDFZeNCure aims to foster collaborative research and enhance scientific excellence at the Institute of
Molecular Genetics and Genetic Engineering, University of Belgrade (IMGGE) in Serbia. This ambitious
initiative brings together IMGGE, with world-renowned research institutions in Germany (MPG), Portugal
(CF) and the United Kingdom (UoS) along with an associated partner from Latvia (BGI RFL). The
overarching goal is to elevate IMGGE's research profile by strengthening its capabilities in zebrafish (ZF)
research, particularly in the context of non-communicable diseases (NCDs).
NCDs pose a significant global health challenge, accounting for over 74% of all deaths worldwide. These
diseases are influenced by a complex interplay of genetic, physiological, environmental, and behavioral
factors. Recognizing the gravity of the situation, the EU has prioritized NCD research under the Cluster 1:
Health of Horizon Europe.
ZeNCure focuses on the critical role of in vivo models in NCD research, ranging from identifying genetic
and environmental risk factors to testing innovative therapeutics. It leverages cutting-edge technologies,
including next-generation sequencing (NGS) and bioinformatics, to enhance IMGGE's capabilities in this
field.
ZeNCure is poised to accelerate the professional development of both early-stage and senior researchers,
as well as administrative staff. This holistic approach will not only enhance IMGGE's competitiveness in
European research funding schemes but also create an inspiring and supportive research environment.
ZeNCure represents a transformative endeavor that aims to strengthen scientific collaboration, improve
research capabilities, and contribute to the global fight against NCDs. By bridging the gap between IMGGE
and leading European research institutions, the project aspires to elevate IMGGE into a competitive and
internationally recognized research institution in the Western Balkans, fostering regional integration and
convergence with the EU.Principal Investigator: Dr Aleksandra Divac Rankov, IMGGEDuration period: 2024-202
Can We Rely on AI?
No full textOver the last decade, adversarial attack algorithms have revealed instabilities in deep
learning tools. These algorithms raise issues regarding safety, reliability and interpretability
in artificial intelligence (AI); especially in high risk settings.
At the heart of this landscape are ideas from optimization, numerical analysis and high
dimensional stochastic analysis. From a practical perspective, there has been a war of
escalation between those developing attack and defence strategies. At a more theoretical
level, researchers have also studied bigger picture questions concerning the existence
and computability of successful attacks. We will present examples of attack algorithms in
image classification and optical character recognition. We will also outline recent results
on the overarching question of whether, under reasonable assumptions, it is inevitable
that AI tools will be vulnerable to attack.Book of abstracts: 5th Belgrade Bioinformatics Conference, Serbia, Belgrade,17-20 june 2024
GENETIC SPECTRUM OF PRIMARY DYSLIPIDEMIAS IN CHILDREN - SINGLE CENTER EXPERIENCE
No full textPrimary dyslipidemias are heterogenous metabolic disorders caused by pathogenic genetic
variants. Over 100 genes have been identified that impact lipid metabolism, with familial
hypercholesterolemia being the most common form, occurring in the general population with a
frequency of 1:200–1:500. Dyslipidemias are considered as one of the most significant risk
factors for atherosclerotic cardiovascular diseases. Detection of primary dyslipidemia in
pediatric population is of crucial importance in preventing lifelong cardiovascular complitations.
Four patients in this series were followed from 2012 to 2024 at the Mother and Child Health
Care Institute of Serbia “Dr Vukan Cupic”. Three patients were identified on the basis of
persistent abnormality in lipid profile with definitive diagnosis established by next generation
sequencing (NGS) methodology. One patient was diagnosed with hyperalphalipoproteinemia on
the basis of incidental NGS finding.
This study presents the clinical features and genetic findings of four pediatric patients with
primary dyslipidemias. The causative variants were detected in the LDLR, APOA5, LIPA and
CETP genes, resulting respectively in familial hypercholesterolemia, familial
hypertriglyceridemia, lysosomal acid lipase (LAL) deficiency and hyperalphalipoproteinemia.
Diagnosis of LAL deficiency prompted the administration of enzyme replacement therapy.
Incidentally found variant in CETP gene is associated with benign hyperalphalipoproteinemia in
a child tested due to sensorineural deafness.
Identification of genetic variants in pediatric patients with primary dyslipidemias provides
valuable insights into the pathogenesis of particular lipid metabolism disorders. More
importantly it enables precise pharmacologic treatment and nutritional management, and
provides opportunity for selective familial screening.VII Congress of the Serbian Genetic Society Zlatibor; October 2 to 5, 2024
Decoding the functional roles of two highly homologous arabidopsis DSS1 genes: analytical approaches and biotechnological implications
No full textExploring the unknown functions of plant genes holds immense importance, not only within
the field of fundamental plant science but also for future biotechnology advancements. Understanding
the molecular mechanisms underlying plant responses to environmental stressors and
developing abiotic stress-tolerant plants are major goals of modern plant science. This research
is dedicated to uncovering functional differences between two closely related Arabidopsis DSS1
proteins in terms of their response to oxidative stress and maintenance of genome integrity. So
far, evidence from the literature indicates that DSS1 proteins, as a group of short, highly conserved
intrinsically disordered proteins, could play a crucial role in ensuring the stability of various biological
complexes. The functional characterization of two Arabidopsis thaliana isoforms, DSS1(I)
and DSS1(V), employed an integrated approach, combining different methods, such as: functional
complementation tests in a heterologous system, CRISPR/Cas9 knockout mutagenesis, overexpression
through the Gateway cloning system, and transcriptome analysis. Expressing AtDSS1(I) in
the Δdss1 mutant of Ustilago maydis restores the phenotypes of mutants sensitive to genotoxic
agents. This finding suggests that AtDSS1(I) is associated with homologous recombination (HR)
and DNA repair. Phenotypic characterization of mutant lines revealed differences in root and stem
lengths, as well as rosette area size compared to wild-type (WT) plants. Disruption of the AtDSS1(V)
gene led to lower survival rates and increased oxidized protein levels under oxidative stress. Phenotypes
of overexpressing lines showed no significant differences in comparison WT plants. RNASeq
analysis identified major gene expression changes in dss1 mutants, particularly in HR-related
pathways and metabolic pathways responsible for the synthesis of secondary metabolites. Our
research reveals that two highly homologous Arabidopsis DSS1 proteins exhibit both distinct and
overlapping functions.Book of abstract: 5th International Conference on Plant Biology (24th SPPS Meeting
Transcriptomic Identification of Dysregulated Genes Underlying Paclitaxel-Induced Multidrug Resistance in Colon Cancer Cells
No full textMultidrug resistance (MDR) is the main cause of therapeutic failure in the treatment of colon cancer.
Systematical approaches are needed to understand the underlying mechanisms and to find new
therapeutic strategies to overcome MDR. The aim of this study was a comparative analysis of
transcriptome profiles of sensitive and paclitaxel-induced multidrug resistant DLD1 cells to identify
genes and pathways associated with resistance to therapeutics used for colon cancer treatment. The
cells grown as adherent cells and spheroids were exposed to the treatment with two types of
therapeutics used for colon cancer treatment: conventional chemotherapeutic drugs (5-fluorouracil,
oxaliplatin and irinotecan) and targeted therapeutics (bevacizumab and cetuximab). Cell viability was
assessed, and among analyzed therapeutics, the highest resistance factor was recorded for oxaliplatin.
The culture medium used for cell cultivation was analyzed by high-performance liquid chromatography
and none of the therapeutics were detected in the medium in which the sensitive or resistant cells were
grown, indicating resistance mechanism independent of drug efflux. Total RNA isolated from
untreated sensitive and resistant spheroids was subjected to the next generation RNA sequencing to
identify differentially expressed genes associated with baseline resistance to therapeutics. The results
identified PIGR as the most upregulated gene in resistant cells. Additionally, genes encoding markers
of cancer stem cells (PROM1 and ISY1-RAB43), modulators of oxidative stress (AKR1B10) and tumor
microenvironment (MMP20), and cell-cell adhesion protein (CLN4) were found to be significantly
dysregulated suggesting their association with the MDR phenotype. According to the Gene Ontology
enrichment analysis, most of upregulated genes were associated with ribosomal processes, while
downregulated genes were predominantly related to cellular responses to chemical stimuli. Considering
that PIGR encodes a protein involved in activation of ribosome pathway, our findings suggest that
targeting PIGR and ribosome biogenesis could be a promising strategy to overcome MDR in different
treatment modalities.Book of abstract: “HDIR-7: Advances in Cancer Research & Treatment” The 7th Meeting of the Croatian Association for Cancer Research with International Participation November 7 & 8, 2024 Hotel International, Zagreb, Croati
Immobilization of yeast cells in biopolymer systems using freeze-drying technique
No full textThe application of advanced yeast cell immobilization techniques has significantly enhanced
beer production processes. This study aimed to immobilize yeast cells (Saccharomyces pastorious)
in alginate-based carriers using the freeze-drying technique. For this purpose, mediumviscosity sodium alginate was utilized. After lyophilization, the resulting powders were
analyzed for cell viability, storage stability, particle size, and moisture content. Morphological
characteristics were examined using scanning electron and optical microscopy. The low
moisture content in the obtained powders indicates that these types of systems are
microbiologically stable. The average diameter of immobilized yeast cells was larger than that
of non-immobilized cells, measuring 7.33±0.97 and 3.21±0.39 µm, respectively. Surface charge
analysis confirmed the physicochemical stability of the immobilized cell systems, showing a
negative surface charge. The low surface charge of free cells indicated a tendency to aggregate,
as confirmed by optical microscopy. SEM micrographs showed successful cell immobilization in
the carriers. The study concludes that the freeze-drying technique is effective for yeast cell
immobilization and suitable for industrial applications, offering high productivity and
maximum cell protection.Twenty-fifth Jubilee Annual Conference YUCOMAT 2024 & Thirteenth World Round Table Conference on Sintering XIII WRTCS 2024, Herceg Novi, Montenegro, September 2 to 6, 202
Towards optimized 3D cancer cell cultures in alginate-based microfiber
No full textIn recent years, the importance of three-dimensional (3D) models in cancer research has been
increasingly recognized, as they better mimic the in vivo tumor microenvironment. However,
each cancer is unique and requires a specific 3D model that can accommodate its needs. The
aim of this study was to develop and optimize a simple, tunable 3D model based on alginate
microfibers that can support cultures of diverse cancer cell types. Microfibers with
immobilized cells were produced by manual extrusion of cell-alginate suspensions (4×106
cells/ml, 1.6-2.8 wt% Na-alginate) into a gelling bath containing Ca2+ or Ba2+ ions for alginate
gelation. The procedure was optimized regarding the microfiber composition suited to
osteosarcoma cells K7M2-wt (i.e., Ca-alginate with or without 2 wt% HAP) or non-small-cell
lung cancer cells NCI-H460 (i.e., Ba-alginate) as well as regarding the needle gauge (22- 25
G), extrusion velocity and gelation time (1-15 min). Live/dead staining of cells revealed that
while the needle size and gelation time did not significantly influence cell viability, extrusion
velocity can have adverse effects on the cells. To valuate this finding, hydrodynamic shear
stresses were calculated, being 2.4-fold higher at high extrusion velocity compared to that at
medium velocity. Additionally, the concentrations of Na-alginate and Ba2+ were shown to
affect the NCI-H460 cell viability so that 2 wt.% Na-alginate and 45 mM Ba2+ yielded optimal
results. 3D cultures of the immobilized cells in optimal microfibers for up to 21 days
demonstrated that the model supports cell viability and proliferation. Treatments with 0.25-20
μM doxorubicin or 0.5-50 μM cisplatin showed that 3D cultured cells exhibit higher resistance
to anticancer drugs compared to traditional 2D cultures, consistent with increased resistance
in patients. Efficient transport of doxorubicin in microfibers was confirmed by mathematical
modeling. Overall, the results demonstrate the potential of the proposed 3D model for use in
cancer research.Twenty-Second Young Researchers Conference – Materials Science and Engineering December 4 – 6, 2024, Belgrade, Serbi
PHARMACOGENOMICS AND PHARMACOTRANSCRIPTOMICS OF ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDHOOD: ON THE WAY TO PERSONALIZED MEDICINE
No full textPersonalized medicine is focused on research disciplines that contribute to the individualization of
therapy, such as pharmacogenomics and pharmacotranscriptomics. Acute lymphoblastic leukemia (ALL)
is the most common childhood malignancy. It is one of the pediatric malignancies with the highest cure
rate, but still a lethal outcome due to therapy accounts for 1–3% of deaths. Further improvement of
treatment protocols is needed through the implementation of pharmacogenomics and
pharmacotranscriptomics. The research study was aimed at discovering pharmacogenetic and
pharmacotranscriptomic markers of response to therapy with thiopurine and glucocorticoid drugs,
methotrexate and vincristine in children with ALL in Serbia. Blood and bone marrow samples from
children with ALL were collected at the University Children's Hospital in Belgrade. Variants in the
studied genes were detected by PCR and Sanger sequencing. The expression level of NUDT15 in
mononuclear cells was determined by real-time PCR. Next-generation sequencing using cancer panel
TruSeq Amplicon, Illumina was also performed to assess drug resistance. Correlation of
pharmacomarkers with clinical parameters was performed using statistical tests. A polygenic risk score
based prediction model for the development of methotrexate-induced hepatotoxicity was developed. A
number of molecular markers responsible for the efficacy, side effects and toxicity of drugs used to treat
ALL, ie. glucocorticoids, vincristine, asparaginase, anthracyclines, thiopurines and methotrexate. Their
application in clinical practice is still insufficient. Research efforts should be focused on analyzing data
and designing predictive models that use machine learning algorithms. Bioinformatics tools and the
implementation of artificial intelligence will help personalized medicine come to life in clinical practice.Book of abstracts: 2nd B&H Symposium of Laboratory Geneticists and Molecular Biologists (with International Participation) May, 202
The axes of biology: a novel axes-based network embedding paradigm to decipher the functional mechanisms of the cell
No full textCommon approaches for deciphering biological networks involve network embedding
algorithms. These approaches strictly focus on clustering the genes’ embedding vectors and
interpreting such clusters to reveal the hidden information of the networks. However, the
difficulty to unambiguously cluster the embeddings of genes in space and the limitations of
the functional annotations’ resources hinder the identification of the currently unknown cell’s
functioning mechanisms from the gene clusters.
We propose a new approach that shifts this functional exploration from the embedding vectors
of genes in space to the axes of the space itself. We assign interpretable and fine-grained
semantic meanings to the axes (basis vectors) that span the embedding space to identify the
functional mechanisms of a cell.
Our axes-based methodology captures 1.32 times more functional information (GO BP
terms associated with the axes) from the embedding spaces than the standard gene-centric
approach (GO BP terms enriched in at least one gene cluster). This captured information is
also better stratified, as GO BP terms associated with the same axis are, on average, 1.42
times more semantically coherent than those enriched in the same gene cluster. Moreover,
it uncovers new data-driven functional interactions that are unregistered in the functional
ontologies, but biologically coherent. We exploit these interactions to define new higher-level
annotations that we validate through literature curation. Finally, we leverage our methodology
to discover evolutionary connections between cellular functions and the evolution of species.Book of abstracts: 5th Belgrade Bioinformatics Conference, Serbia, Belgrade,17-20 june 2024