imagine (Institute of molecular genetics and genetic engineering)
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Insight into immunoregulatory and neuromodulatory capability of Bacteroides cellulosilyticus and Bacteroides xylanisolvens human gut microbiota isolates
No full textAlterations in the abundance of Bacteroides species are linked to the disruption of the intestinal epithelial barrier and chronic inflammation and has been increasingly recognized as a factor in the development of neurological and neuropsychiatric disorders. Nevertheless, the exact role of Bacteroides species in the gut-brain cross-talk is still largely unexplored. Here, we investigated the immunoregulatory and neuromodulatory potential of two poorly characterized Bacteroides species, including Bacteroides cellulosilyticus and Bacteroides xylanisolvens. The results revealed that both Bacteroides isolates reduced inflammation in Caco-2 intestinal epithelial cells by decreasing the level of IL-8 chemokine and transcription of NF-kB, the two key factors involved in gut inflammation development and barrier disruption. In addition, the Bacteroides strains in the co-culture of Caco-2 cells and phytohemagglutinin-stimulated PBMCs reduced the production of pro-inflammatory cytokines TNF-α and IL-1β, as well as Th1-polarizing IFN-γ cytokine. Finally, in Caenorhabditis elegans, Bacteroides strains differently modulated the expression of the genes implicated in GABA, serotonin and dopamine signaling and synaptic vesicles release pointed to the strain-specific effects of these isolates on neural function. Altogether, these in vitro results show that tested Bacteroides strains may exert anti-inflammatory and neuromodulatory effects, indicating their potential role in microbiota-gut-brain axis
Novel cellular factors involved in regulation of BRCA2-driven homologous recombination in Ustilago maydis
No full textMaintaining genome integrity is critical for all organisms, requiring efficient DNA repair mechanisms to counteract damage from both internal and external sources. Homologous recombination (HR) is a conserved and accurate pathway for repairing DNA double-strand breaks (DSBs). While yeast uses Rad52 as a central HR mediator, higher eukaryotes, including humans, rely on BRCA2. The phytopathogenic fungus Ustilago maydis possesses a BRCA2 homolog, Brh2, and an HR system strikingly similar to that of humans, making it an excellent model for studying recombination. To uncover novel HR regulators, we conducted a genetic screen for suppressors of hydroxyurea (HU) sensitivity in blm mutants. Blm encodes a RecQ-family helicase, and its loss causes defects in replication-associated repair. The screen identified eight suppressor genes: three known HR factors (rad51, dna2, and mph), paraplegin (nuclear-encoded metalloprotease protein that is a member of the AAA protein family, that is located to the inner mitochondrial membrane) and four novel genes—rec3, zdr1, bls9, and bls2. • Rec3 is a Rad51-family ATPase essential for allelic recombination and meiosis, and shows a strong functional connection with Brh2. • Zdr1 is a C2H2-type zinc finger protein; although its deletion does not overtly affect HR, it contributes to general DNA repair processes. • Bls9 and Bls2 are uncharacterized proteins, but Bls9 is involved in HR between chromosome homologs, while Bls2 shows a slow-growth phenotype. Importantly, deletions of rec3, zdr1, bls2, and paraplegin also suppress HU sensitivity in Δgen1 and Δmus81 mutants, suggesting broader roles in recombination-associated repair. In contrast, bls9 deletion does not rescue HU sensitivity in Δgen1, indicating functional specificity. These newly identified factors expand our understanding of HR regulation and provide insights into the complexity and coordination of DNA repair pathways in eukaryotic cells.Book of abstract: 8th EU-US Conference on endogenous DNA damage and repair, TRONDHEIM, NTNU October 5th—8th | 202
A New Approach in Identifying dss1 Suppressors by Whole Genome Sequencing of Ustilago maydis
No full textDss1, a small and intrinsically disordered protein, is one of the crucial regulators of homologous recombination (HR), a key DNA repair pathway that ensures error-free repair of double-strand breaks, thereby preserving genome stability. Dss1 is highly conserved in eukaryotes and is present in a model organism Ustilago maydis, known for its extreme resistance to ionizing and UV irradiation. This microorganism is a valuable model for investigating HR, which combines high genetic tractability and a DNA-repair system remarkably similar to humans’, including conserved BRCA2 ortholog Brh2 and its partner Dss1.
Loss of dss1 function leads to the extreme sensitivity of the U. maydis mutant to genotoxic agents due to impaired DNA-repair and HR. The main aim of the research is to identify novel cellular factors involved in HR by searching for suppressors of dss1, secondary mutations that rescue genotoxic resistance of dss1 mutant.
To uncover such suppressors, several independent Δdss1 suppressor strains were generated by random mutagenesis and phenotypically characterized. While complementation cloning, classical genetic approach, could not reveal the suppressor identity, we applied whole-genome sequencing in combination with a modified pooled-linkage analysis. This strategy is based on sequencing DNA from pools of meiotic segregants, grouped according to their expected phenotype. By separating putative suppressor and wt segregants, it becomes possible to track how often specific variant appear in each pool. Variants that consistently co-segregate with the expected suppressor phenotype show a shift in allele frequency, which points to genomic regions that are likely to carry the suppressor mutation. Although the analysis is ongoing, the study demonstrates the applicability of pooled-linkage sequencing as a complementary method to classical genetic tools. The approach has the potential to facilitate the identification of novel factors involved in HR in U. maydis, thus, representing an applicable framework for uncovering genetic networks that maintain genome integrity.Book of abstract: 8th edition of Young Biologists Matter Congress (Molecular Biology & Physiology) Thessaloniki, Greece, 29th September – 4th October 202
The effect of the fibroblast secretome from the blind mole rat (Nannospalax leucodon) on HCT116 colon cancer cells
No full textSlepo kuče iz roda Nannospalax (Palmer 1903) je podzemni glodar koji veći deo života
provodi u sistemima tunela, u ekstremno hipoksičnim i hiperkapničnim uslovima, u potpunoj
tami. Telo je malo, čvrsto, bez repa, prekriveno gustim krznom sive boje sa jakom lobanjom bez
spoljašnjeg uha, sa izraženim donjim sekutićima koji služe za kopanje (Slika 1). Ekstremiteti su
kratki, zbog čega spadaju u vrste sa malom stopom disperzije. Na površinu izlaze retko, mahom
radi parenja ili potrage za hranom. Termin „slepo“ nije sasvim adekvatan, oči na glavi nisu
vidljive, ali je prisutan par rudimentarnih očiju ispod kože, koje i dalje omogućavaju
prepoznavanje svetlosti i tame, odnosno razlikovanje dana i noći1
. Pored morfoloških adaptacija
na podzemni način života, razvili su niz fizioloških i genetičkih specifičnosti, zbog čega
predstavljaju dragocen model-organizam u različitim oblastima istraživanja, uključujući
toleranciju na hiperkapniju i hipoksiju, otpornost na rak i dugovečnost, cirkadijalne ritmove i
senzornu neurobiologiju
WORM_PROFILER: THE ECHINOCOCCUS SPP. DATABASE FOR SERBIA
No full textObjectives: Echinococcus spp. tapeworms are endemic in Serbia. Reporting of human
and animal cases is mandatory, but the records are maintained in separate databases.
Records on widlife echinococcosis are scarce. To facilitate the development of
systematic monitoring of Echinococcus spp. transmission and strategies for targeted
control, a unified database of all confirmed cases is necessary.
Materials and methods: GPS data was used to map the origin of the tapeworm host by
Geographic Information System (GIS) software. Multiplex PCR has been used for the
detection and speciation of the tapeworm (Cox1 and/or Nad1 gene).
Results: Thus far, n = 170 samples of individual animals, representing two definitive host
species and three intermediate, were screened for the presence of the tapeworm. Eleven
samples were positive. The database displays a map of confirmed cases, the host species,
tapeworm species and haplogroup. Entry of the Cox1 sequences is pending. A serch
function for all parameters has been enabled, a data retrieval function is pending.
Conclusion: The Worm_Profiler database will facilitate a One Health approach to
echinoccosis in Serbia, by providing a platform for accessing information on confirmed
animal cases, focusing particularly on wildlife, to the scientific community, veterinarians,
physicians and the general public.Book of abstract: 57th Days of Preventive Medicine, International Congress Contemporary Challenges in Public Health, 23-26. September 2025. Niš, Serbi
Violacein kao potencijalni agens za terapiju sarkoma
No full textSarcomas, particularly pediatric types such as rhabdomyosarcoma and osteosarcoma, remain difficult to
treat due to limited therapeutic efficacy and significant toxicity of current regimens. Natural compounds
are gaining attention as potential alternatives or adjuvants in sarcoma therapy. Among them, violacein, an
indole-derived pigment produced by Chromobacterium violaceum, has demonstrated promising antitumor
effects across several cancer types. This review outlines the biological features of violacein, as well as its
anticancer properties, particularly in sarcoma models. Current evidence highlights violacein’s ability to
selectively target tumor cells by inducing apoptosis and inhibiting cell migration. Mechanistic insights
and observed effects in sarcoma models are discussed. Additionally, formulation and delivery challenges
are addressed, along with strategies to enhance its therapeutic potential. By synthesizing current findings,
this review positions violacein and similar compounds as compelling candidates for further investigation
in the context of sarcoma therapy.Sarkomi, posebno pedijatrijski tipovi kao što su rabdomiosarkom i osteosarkom, i dalje predstavljaju
terapijski izazov zbog ograničene efikasnosti trenutnih režima lečenja i značajne toksičnosti postojećih
hemioterapeutika. Prirodna jedinjenja sve više privlače pažnju kao potencijalne alternative ili adjuvansi u
terapiji tumora. Među njima, violacein, indolski pigment koji proizvodi Chromobacterium violaceum,
pokazao je obećavajuće efekte na različitim tipovima tumora. Trenutni dokazi ukazuju na sposobnost
violaceina da selektivno deluje na tumorske ćelije indukujući apoptozu i inhibirajući migraciju ćelija. Ovaj
pregled opisuje biološke karakteristike violaceina, kao i njegova antitumorska svojstva, posebno na
modelima sarkoma. Posebna pažnja posvećena je novim uvidima u mehanizme njegovog delovanja. Pored
toga, diskutovani su izazovi vezani za formulaciju i isporuku violaceina, zajedno sa strategijama za
unapređenje njegovog terapeutskog potencijala. Sintezom postojećih saznanja, ovaj pregled pozicionira
violacein i slična jedinjenja kao perspektivne kandidate za dalja istraživanja u kontekstu terapije sarkoma
Cancer 3D Models: Essential Tools for Understanding and Overcoming Drug Resistance
No full textAnticancer drug resistance remains a major challenge in cancer treatment hindering the efficacy of
chemotherapy and targeted therapies. Conventional two-dimensional (2D) cell cultures cannot replicate the complexity of the in vivo tumor microenvironment (TME), limiting their utility for drug resistance research. Therefore,
three-dimensional (3D) tumor models have proven to be a promising alternative for investigating chemoresistance
mechanisms. In this review, various cancer 3D models, including spheroids, organoids, scaffold-based models, and
bioprinted models, are comprehensively evaluated with a focus on their application in drug resistance studies. We
discuss the materials, properties, and advantages of each model, highlighting their ability to better mimic the TME
and represent complex mechanisms of drug resistance such as epithelial-mesenchymal transition (EMT), drug efflux,
and tumor-stroma interactions. Furthermore, we investigate the limitations of these models, including scalability,
reproducibility and technical challenges, as well as their potential therapeutic impact on personalized medicine.
Through a thorough comparison of model performance, we provide insights into the strengths and weaknesses of each
approach and offer guidance for model selection based on specific research needs
SEASONAL DYNAMICS OF METAL AND BIOCIDE RESISTANCE GENES IN AIRBORNE METAGENOMES ACROSS BELGRADE
No full textAir as a vector for resistance gene dissemination remains understudied, particularly regarding
genes conferring resistance to metals and biocides, which are often co-located with antibiotic
resistance genes on mobile genetic elements. This study analyzed the diversity and abundance
of such resistance genes in airborne metagenomes collected from sites across Belgrade, Serbia,
during autumn and winter of 2024/2025. Air samples were collected using hydrophobic
polypropylene membrane filters, DNA was extracted by the phenol-chloroform method,
sequenced on the Illumina NovaSeq X Plus platform, and analyzed using the AMR++ v3.0
pipeline with the MEGARes database. The diversity and abundance of both metal and biocide
resistance genes were more pronounced in autumn, while winter samples showed greater
uniformity across sites. Quaternary ammonium compounds (QACs) and multibiocide
resistance genes dominated in 5 of 7 sites in autumn, reaching 70.4% in Leštane, 68.4% in
Zeleno Brdo, and 63.3% in Veliki Crljeni for QACs. Barajevo and Borča lacked QACs in
autumn and, along with all sites in winter, were dominated by multibiocide (up to 39.9%) and
acid resistance genes (up to 39.4%). In winter, QACs were entirely absent. For resistance to
metals, autumn samples were dominated by multimetal (up to 61,4%) and copper (up to
28.9%), with iron resistance genes uniquely abundant in Despota Stefana (13.5%). In winter,
iron resistance extended to Leštane (1.9%) and Veliki Crljeni (5.1%), alongside broader
representation of zinc (up to 11.4%) and nickel resistance genes (up to 9.2%). These findings
emphasize seasonal and spatial variability in airborne resistomes and the role of environmental
pressures in shaping their composition in Belgrade.Zbornik sažetaka: V simpozijum biologa i ekologa Republike Srpske sa međunarodnim učešćem - SBERS 2025 Prirodnomatematički fakultet, Univerzitet u Banjoj Luci, 13-15. novembar 2025
Beyond colonization: Candida albicans exhibits substantial pathogenic potential in cystic fibrosis environments
No full textCystic fibrosis (CF) sputum represents a highly permissive niche for microbial colonization, yet the contribution of Candida albicans to disease progression remains insufficiently investigated despite its frequent detection in CF airways. We hypothesized that the heterogeneous nature of CF lung, reflected through the emergence of oxygen-depleted niches during disease progression, modulates C. albicans pathogenicity and antifungal susceptibility. Using complementary in vitro and in vivo approaches, we show that clinical CF isolates of C. albicans are virulent in CF-mimicking environments. Synthetic CF medium (SCFM2) supported robust filamentation, with oxygen-nutrient interplay critically shaping fungal growth and drug response. In a novel CF infection model using zebrafish morphants, we observed heightened susceptibility to C. albicans compared to wild-type embryos. Reporter strains showed elevated ECE1 expression, indicating increased candidalysin production and virulence in vivo. Our study provides compelling evidence that CF isolates of C. albicans have pathogenic potential, warranting consideration in future therapeutic strategies
Assessing Internal Consistency of the Autism Spectrum Disorder Gastrointestinal and Related Behaviors Inventory and the Frequency and Socio-Emotional Correlates of Gastrointestinal Difficulties in Children With the Autism Spectrum Disorder: A Cross-Sectional Study
No full textGastrointestinal (GI) difficulties are common in children diagnosed with autism spectrum disorder (ASD). However, these difficulties can frequently remain unrecognized. Therefore, we aimed to translate a newly developed instrument, The Autism Spectrum Disorder Gastrointestinal and Related Behaviors Inventory in Children (ASD-GIRBI), to assess its reliability and to explore the frequency of various gastrointestinal difficulties and related behaviors, as well as to explore the association of GI difficulties with the measures of social functioning and emotional and behavioral difficulties in children with ASD. A total of 98 children and adolescents (aged 4–18 [M age = 10.67 ± 3.705], 82.7% male), previously diagnosed with ASD at the Institute of Mental Health in Belgrade, Serbia, took part in this research. Their parents filled out the following questionnaires: ASD-GIRBI (an assessment of gastrointestinal and related symptoms), Stanford Social Dimensions Scale (SSDS) (a measure of social functioning) and Strengths and Difficulties Questionnaire (SDQ) (a measure of emotional and behavioral problems). Our results indicate that the ASD-GIRBI is a reliable instrument for GI difficulties assessment (Cronbach's α = 0.841) with the total score successfully discriminating between the participants with and without a GI disorder diagnosis (p = 0.040). Any gastrointestinal symptom was present in 54.1% of the participants, most commonly flatulence, diarrhea, and constipation. The severity of gastrointestinal difficulties correlated to emotional problems (r = 0.261, p < 0.01), conduct problems (r = 0.219, p < 0.05), hyperactivity (r = 0.381, p < 0.01), peer problems (r = 0.266, p < 0.01), total difficulties (r = 0.454, p < 0.01) and total difficulties impact (r = 0.321, p < 0.01). Our data emphasize the potential importance of GI difficulties for various areas of functioning of individuals with ASD