imagine (Institute of molecular genetics and genetic engineering)
Not a member yet
3088 research outputs found
Sort by
GENOMICS AS A BASIS FOR PRECISION MEDICINE
No full textBackground: Although medicine always aimed to be personalized, true implementation of
personalized medicine in health care practice has started recently. Fascinating progress of molecular
genetics has strongly contributed to this great achievement of modern medicine. Personalized
medicine, also known as genome-based medicine and precision medicine, uses the knowledge of
molecular basis of the disease in order to individualize treatment for each patient.
Methods: Development of novel powerful high-throughput technologies has enabled better insight
into “oms” landscape of many diseases, resulting in application of precision medicine approaches in
their treatment.
Results: There are four cornerstones of modern precision medicine: “omics”-based diagnostics,
pharmacogenomics, specific molecular targeted, gene and cellular therapy and predictive genomics.
One of the most important successes of precision medicine is a discovery of novel diagnostic molecular
markers. Furthermore, numerous newly discovered molecular markers have contributed to more
precise classification of patients in distinct prognostic groups, leading to specific, more successful
treatment protocols. Development of pharmacogenomics platforms and application of molecular–
targeted therapy have led to the individualization of therapy, tailored to genetic profile of a disease in
each patient. The development of gene therapies which can cure or prevent a disease by targeting
disease-causing molecular defect has confirmed that the precision medicine has responded
successfully to a great challenge. Additionally, cellular and tissue therapies have opened new
possibilities for personalized treatment of many patients. Growing knowledge in predictive genomics
leads to the preventive medicine, the most important goal of modern medicine.
Conclusion: There is no doubt that we are getting closer to full implementation of precision medicine
in every day clinical practice.32nd Meeting of the European Society of Paediatric Clinical Research (ESPCR) in Opatija, Croatia, May 24-25, 2024
POPULATION PHARMACOGENOMICS OF IMMUNOSUPPRESSIVE AND AMINOSALICYLATE THERAPY: POTENTIAL FOR THERAPY OPTIMIZATION IN SERBIAN PAEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS
No full textBackground: Inflammatory bowel disease (IBD) is a chronic inflammation of gastrointestinal tract (GIT)
represented by two types of the disease – ulcerative colitis where colon is primarily affected and
Chron’s disease with the entire digestive tract affected. In paediatric patients, IBD symptoms appear
to be more severe than in adults. This complex condition is characterized by strong variability in
phenotype and prognosis. Also, adverse drug reactions caused by drugs used in therapy of IBD are
often more severe in children then adults. We aimed to determine frequencies of variants in
pharmacogenes relevant for therapeutic success of immunosuppressants and aminosalicylates
administrated to paediatric IBD patients.
Methods: Genomic data of 895 Serbian paediatric patients were obtained by clinical (TruSight One,
Illumina) or whole exome (Exome 2.0 Plus, Illumina) sequencing. Pharmacogenomics variants of 6-
mercaptopurine, methotrexate, tacrolimus and sulfasalazine drugs response were selected for analysis
based on PharmGKB and CPIC databases: CPIC Level Final (TPMT, NUDT15, CYP3A5, G6PD) or CPIC
Level Provisional (CYP3A4, ABCB1, SLCO1B1, NAT2).Variant call format files (VCF) were created from
FASTQ files using in-house pipeline for alignment and annotation. Calling of star alleles was performed
using Stargazer bioinformatics tool and subsequent analysis of frequency differences in Serbian and
general European subpopulations were done using 1000 Genomes Project database, Chi square test
and R program.
Results: Alleles called in CYP3A5, G6PD and TPMT genes showed no differences comparing to other
European populations. Among Serbian paediatric cohort heterozygous diplotype TPMT *1/*3C
harbouring only variant rs1142345 C was less frequent than in overall European, Central European,
British and Ibearian populations. Significantly different frequencies in Serbian paediatric cohort versus
European subpopulations were found for nine haplotypes, one in ABCB1 and NUDT15 genes, two
haplotypes in CYP3A4 and NAT2 genes and three haplotypes in SLCO1B1 gene. Four haplotypes were
not observed in European population according to CPIC, but were present in our cohort, mainly *10,
*16 and *179 in G6PD gene and *10 in NAT2.
Conclusion: Results presented herein show that frequencies of several important pharmacogenomics
variants differ in Serbian and other European subpopulations. This could have serious clinical
implications and potential more frequent development of adverse drug reactions when treating
paediatric IBD patients and other patients in need with standard doses of immunosuppressive therapy.
Population-specific pharmacogenomics aspect should be taken into account for therapy optimization
in clinical practice, especially for vulnerable patients groups namely paediatric patients.32nd Meeting of the European Society of Paediatric Clinical Research (ESPCR) in Opatija, Croatia, May 24-25, 2024
Isolation and identification of novel glyphosate-degrading bacteria from soil samples in Serbia
No full textGiven the presence and abundance of bacteria
in diverse and even extreme conditions, and their
metabolic diversity, microbial biodegradation
poses as a promising approach towards the
removal of contaminants from the environment.
As part of our research for the discovery of new
enzymes degrading glyphosate, a widely used
pesticide, we isolated bacteria with the ability to
grow on glyphosate. Five soil samples from
Serbia were used, one from a forest and four from
agricultural intensive areas. Microorganisms have
been isolated from soil samples using different
media including ones with glyphosate as sole
source of carbon. The morphologically different
colonies and the fastest growers were selected for
further analysis. Seven best candidates were
identified by 16S rRNA sequencing. The resulting
sequences were analyzed by BLAST, and it was
shown that some of the isolates belong to genera
which have not previously been reported to
degrade glyphosate, including Cupriavidus,
Lelliottia and Pseudescherichia.
Biotransformations of glyphosate which ran for up
to 11 days using whole cells were monitored with
TLC for glyphosate transformation and HPLC
analysis was also used, in order to confirm the
degradation and investigate the presence of other
degradation products. Overall, our analysis has
identified potential new species with glyphosate
degrading activityThe 2nd Annual Bio3 Forum took place at Technopolis Gazi in Athens from September 1st to
5th, 2024. Th
Nanohybridosomes from spruce needles
No full textSiN-EV Meeting 2024, 17th of September 2024
Session 3 Short presentation
The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes
No full textAstrocytes are the main homeostatic cells in the central nervous system able to
respond to pathological conditions by transforming from quiescent to reactive state
throughout the process known as reactive astrogliosis. This is a compensatory
response that mediates tissue damage and recovery. During this process mature
astrocytes reacquire some of precursor properties, but the underlying molecular
mechanisms are still not fully understood. We focused our research on the
reactivation-related functional properties of astrocytes governed by transcription
factors SOX2 and SOX9. These transcription factors have important roles during
gliogenesis, they are downregulated in mature astrocytes and re-expressed in
reactive astrocytes. Initial screening of SOX2 and SOX9 expression after
sensorimotor cortex ablation injury in rat was performed using
immunohistochemistry. Further gain-of-function studies were done in vitro using
astrocytes derived from NT2/D1 cell line (NT2/A). SOX2 and SOX9 were overexpressed
in mature NT2/A by lentiviral transduction. The proliferative capacity of
NT2/A cells following SOX2 and SOX9 over-expression was analyzed by
immunostaining of Ki67, a nuclear protein associated with cellular proliferation.
Additionally, wound-scratch assay was conducted to investigate the migratory
potential of NT2/A cells post-SOX2 and SOX9 over-expression. The initial
screening of SOX2 and SOX9 expression after brain injury in rat sensorimotor
cortex showed up-regulation of these transcription factors in reactive astrocytes in
the vicinity of the lesion area. In vitro functional studies showed that SOX2 overexpression
leads to an increase in NT2/A proliferation and SOX9 over-expression
promotes migration of NT2/A. The study highlights the importance of SOX2 and
SOX9 in regulating the functional properties of astrocytes during reactive astrogliosis. The results imply that modulation of SOX genes expression may change
the functional properties of astrocytes that holds the promise for discovery of
potential therapeutic targets in development of novel strategies for tissue
regeneration and recoveryBook of abstracts: Belgrade Neuroscience Next Hub 2024 with international participation
24-25 May 2024. Belgrade, Serbi
Influence of promoter variants of uridine-diphosphateglucuronosyltransferase 1A1 gene on bilirubin metabolism and significance of UGT1A1*28 variant as pharmacogenetic markers
No full textGlukuronidacija je nezaobilazan korak u metabolizmu i ekskreciji bilirubina. Ekskluzivnu ulogu u ovom
procesu ima enzim UGT1A1 kodiran UGT1A1 genom. Do sada je opisano 130 varijanti ovog gena. Wildtype
UGT1A1*1 u svom promotorskom TATA regionu sadrži 6 TA ponovaka. Sa povećanjem TA ponovaka
u promotorskom regionu smanjuje se aktivnost promotora i posledično tome i aktivnost UGT1A1 enzima.
Opisane su promotorske varijante UGT1A1*36, UGT1A1*28 i UGT1A1*37 sa 5, 7 i 8 TA ponovaka, respektivno.
Smanjenjem aktivnosti UGT1A1 enzima dolazi do hiperbilirubinemije i ikterusa, kao i do pojave Žilberovog
sindroma (ŽS) koji se smatra benignim kliničkim stanjem. Najčešći uzrok ŽS je prisustvo UGT1A1*28
varijante u homozigotnom stanju. Značajno je i to da je ustanovljeno da učestalost ove varijante pokazuje
izrazitu populacionu specifičnost. Osim toga UGT1A1*28 alel je značajan farmakogenetički marker za brojne
farmaceutike, a posebno je značajan za lek irinotekan. Detekcija UGT1A1*28 se takođe može koristiti za
diferencijalnu dijagnozu hepatitisa C i sumnje na druga oboljenja jetre. Istovremeno, varijante gena
UGT1A1 tretiraju se kao tercijarni modifikatori kod sindroma β-talasemije minor i drugih hemolitičkih
anemija.Glucuronidation is an indispensable step in the metabolism and excretion of bilirubin. An exclusive role
in this process is played by the enzyme UGT1A1, encoded by the UGT1A1 gene. 130 variants of the UGT1A1
gene have been described. Wild-type UGT1A1*1 contains 6 TA repeats (TA6) in its promoter TATA region.
With the increase in TA repeats in the promoter region, the activity of the promoter decreases and
consequently the activity of the UGT1A1 enzyme will be reduced. Described promoter variants are
UGT1A1*36, UGT1A1*28, and UGT1A1*37 with 5, 7, and 8 TA repeats, respectively. A decrease in the activity
of the UGT1A1 enzyme leads to hyperbilirubinemia and the appearance of Gilbert's syndrome (GS)
considered a benign clinical condition. The most common cause of GS is the presence of UGT1A1*28 in a
homozygous state. Also, it was established that the frequency of this variant shows a distinct population
specificity. In addition, the UGT1A1*28 allele is an important pharmacogenetic marker for numerous
pharmaceuticals, and for drug irinotecan it is particularly important. Detection of UGT1A1*28 can also be
used for the differential diagnosis of hepatitis C and other suspected liver diseases. At the same time,
UGT1A1 gene variants are treated as tertiary modifiers in β-thalassemia minor syndrome and other
hemolytic anemias
Decoding Pyocin Import Mechanisms: Insights for Antibiotic Development
No full textPiocins are a diverse group of bacteriocins, protein antibiotics produced by strains of the bacterium
Pseudomonas aeruginosa. This bacterium has been declared a priority pathogen for the development of
new antibiotics by the World Health Organization, because some strains are resistant to all currently
available antibiotics. Piocins are highly specific and potent antibiotics that could be used to combat
resistant strains of this bacterium, particularly in the case of chronic infections in immunocompromised
individuals. This chapter provides an overview of new discoveries related to the mechanism of action of
piocins and how these multi-domain protein antibiotics traverse the bacterial cell wall. Our journey begins
with TonB-dependent receptors that transport piocins across the outer membrane, and concludes with the
TonB system and the FtsH protease and their activity in transferring piocins through the inner membrane.
Also, the structural parts of piocins involved in various stages of their uptake into the bacterial cell will be
discussed. Additionally, the molecular-biological methods currently used to study the process of piocin
uptake will be presented. The aim of the chapter is to explain how understanding the molecular details of
piocin uptake can assist in their development into a new group of potent antibiotics.Piocini su raznovrsna grupa bakteriocina, proteinskih antibiotika koje produkuju sojevi bakterije
Pseudomonas aeruginosa. Ova bakterija je od strane Svetske zdravstvene organizacije proglašena za
patogena od prioriteta za razvoj novih antibiotika, zato što su pojedini sojevi rezistentni na sve trenutno
dostupne antibiotike. Piocini su visoko-specifični i potentni antibiotici koji mogu pronaći primenu u
suzbijanju rezistentnih sojeva ove bakterije, a naročito u slučaju hroničnih infekcija kod
imunokompromitovanih osoba. Ovo poglavlje daje prikaz novih otkrića koja se odnose na mehanizam
delovanja piocina, i način na koji ovi višedomenski proteinski antibiotici prolaze kroz bakterijski ćelijski
zid. Priča započinje sa TonB zavisnim receptorima koji prenose piocine preko spoljašnje membrane, a
završava sa TonB sistemom i FtsH proteazom i njihovom aktivnošću u prenosu piocina kroz unutrašnju
membranu. Takođe ćemo se osvrnuti na delove u strukturi piocina koji su angažovani u pojedinim fazama
njihovog unosa u bakterijsku ćeliju. Prikazaćemo i molekularno-biološke metode koje se trenutno koriste
za izučavanje procesa unosa piocina. Cilj poglavlja je da objasni kako poznavanje molekularnih detalja o
unosu piocina može pomoći njihov razvoj u novu grupu potentnih antibiotika
EXPRESSION PATTERN OF LONG NON-CODING RNA GAS5 IN PLASMA SAMPLES AND BONE MARROW MONONUCLEAR CELLS FROM MULTIPLE MYELOMA PATIENTS: PRELIMINARY RESULTS
No full textUvod: GAS5 (transkript 5 specifičan za zaustavljanje rasta) je duga nekodirajuća
RNK koja ima ulogu u patogenezi mnogih malignih oboljenja. Međutim, klinički
značaj ekspresije GAS5 u multiplom mijelomu (MM) nije ispitivan.
Cilj: Određivanje nivoa ekspresije GAS5 kod pacijenata sa MM i analiza njegove
povezanosti sa kliničkim i laboratorijskim karakteristikama, prognostičkim skorovima,
terapijskim odgovorom (ORR), vremenom do progresije bolesti (PFS) i
ukupnim preživljavanjem (OS).
Metode: U istraživanje je uključeno 36 pacijenata sa MM koji su dijagnostikovani
u Kliničko-bolničkom centru (KBC) „Bežanijska kosa” i KBC „Zemun” u periodu od
novembra 2022. do maja 2024. godine. Analiza je urađena na 63 uzorka: (36 uzoraka
plazme i 27 uzoraka aspirate koštane srži) i 10 kontrola. Ekspresija GAS5 je
detektovana metodom kvantitativne RT-PCR, korišćenjem TaqMan hemije. Analiza
relativne GAS5 ekspresije je rađena pomoću komparativne ddCt metodologije.
Rezultati: U grupi je bilo 23(63,8%) muškarca i 13 žena (36,2%). 24 (66,6%)
pacijenta je bilo starije od ≥ 65godina. Visokorizične citogenetske aberacije su
registrovane kod 13 (36,1%) pacijenata. Povoljan terapijski odgovor je postignut
kod 17 (62,96%), a kod 9 pacijenata lečenje je u toku. Ekspresija GAS5 u plazmi i
koštanoj srži pacijenata sa MM je značajno niža u odnosu na kontrolne uzorke (p
= 0,04; p < 0,001). Međutim, nije pronađena povezanost između ekspresije GAS5
i kliničkih karakteristika, prognostičkih skorova, ORR, PFS i OS.
Zaključak: Snižen nivo ekspresije GAS5 ukazuje na njegovu ulogu u patogenezi
MM. Rezultati ukazuju da nivo njegove ekspresije nema uticaja na prognozu bolesnika
sa MM, ali za donošenje definitivnih zaključaka neophodno je sprovesti
dalja istraživanja na većoj grupi bolesnika.Introduction: GAS5 (growth arrest-specific 5 transcript) is a long non-coding
RNA known to play a role in the pathogenesis of many malignant diseases. However,
the significance of GAS5 expression in multiple myeloma (MM) has not been
investigated.
Objective: To determine the expression levels of GAS5 in MM patients and analyze
its association with clinical and laboratory characteristics, prognostic scores,
overall response rate (ORR), progression-free survival (PFS) and overall survival
(OS).
Methods: The study included 36 MM patients diagnosed at the Clinical Hospital
Center (CHC) Bežanijska kosa and CHC Zemun between November 2022 and May
2024. A total of 63 samples were analyzed: 36 plasma samples, 27 bone marrow
samples, and 10 controls. GAS5 expression was detected using quantitative RTPCR
with TaqMan chemistry. Relative GAS5 expression analysis was performed
using comparative ddCt methodology.
Results: The study group consisted of 23 (63.8%) males and 13 (36.2%) females.
Twenty-four patients (66.6%) were aged 65 years or older. High-risk cytogenetic
abnormalities were observed in 13 (36.1%) patients. Favorable treatment
response was achieved in 17 (62.96%) patients, with 9 patients still undergoing
treatment. GAS5 expression in plasma and bone marrow of MM patients was significantly
lower compared to control samples (p = 0.04; p < 0.001). However,
no association was found between GAS5 expression and clinical characteristics,
prognostic scores, ORR, PFS or OS.
Conclusion: Reduced GAS5 expression indicates its role in MM pathogenesis.
The results suggest that GAS5 expression levels do not influence the prognosis of
MM patients, but further research on a larger patient cohort is necessary to draw
definitive conclusions.Book of abstract: NACIONALNI KONGRES 6. KONGRES HEMATOLOGA SRBIJE, NATIONAL CONGRESS 6TH CONGRESS OF HEMATOLOGISTS OF SERBIA, Hotel Crowne Plaza, Beograd 17–19. oktobar 2024. godin
Towards Implementing Genetic Information in Health Care and Prevention
No full textVariance among individuals in disease susceptibility, treatment response and/or
progression, is determined -in part- by genetic variation. Human genome sequencing has
uncovered hundreds of millions of genetic variants, while DNA analysis technology has
progressed to allow sequencing a human genome in <24hours, and to analyze millions of
SNPs in millions of DNA samples using arrays.
Array technology has identified thousands of genetic factors for common disease by
Genome Wide Association Studies (GWAS) in cohort studies and biobanks. Thousands of
SNPs associated with disease risk for hundreds of diseases, have been combined in many
disease-specific Polygenic Risk Scores (PRS). Some PRS are now evaluated in clinical trials
to assess their added value in risk prediction, e.g. in population screening programs such
as mammography for breast cancer. Interestingly, such PRS-es and clinically relevant DNA
variants can be assessed using array genotyping (< 30 euro’s/sample).
World-wide large-scale sequencing projects are now ongoing, such as the European 1
million Genomes (1MG) Project, and stimulate national genome programs. The recently
funded Genome of Europe (GoE) project will target to whole genome sequence (WGS)
100,000 citizens from 29 countries across Europe. Such WGS data will be made accessible
for research and applications in care and prevention, such as comparison of particular DNA
variations across ethnic groups and countries, specifying the population genetic structure
of subgroups in the general population, and optimizing imputation capacity against
improved genomic reference data.
Together, these developments have led to genetic information now entering the
hospital clinic, whereby –in theory- all patients can be assessed by array genotyping
for mutations, PRS, pharmacogenetics (PGx), and blood group/HLA typing for example,
to help clinicians in decision making for diagnosis and treatment, and to provide selfempowerment
for patients for prevention. Such a program, called GOALL (Genotyping On
ALL patients) is currently running at Erasmus MC, The Netherlands. However, also outside
of the (academic) hospital setting applications of using genetic information are explored,
such as in population screening programs for breast or colon cancer. Aspects of these
developments and outlooks to the future will be discussed.Book of abstracts: 5th Belgrade Bioinformatics Conference, Serbia, Belgrade,17-20 june 2024
Future directions in network biology
No full textrevolutionized understanding of cellular functions and diseases. The field, which has existed
for two decades, has witnessed rapid evolution, accompanied by emerging challenges. These
challenges stem from various factors, notably the growing complexity and volume of data
together with the increased diversity of data types describing different scales of biological
organization.
This talk will discuss some of key research areas in network biology and highlight recent
breakthroughs in these areas; offer a perspective on the future directions of network biology;
and touch on scientific communities, educational initiatives, and the importance of fostering
diversity within the field.
Two specific research directions will be discussed. The first is on our network-of-networks
analyses of multi-scale biological systems with application to protein function prediction. The
function of a protein is determined by the protein’s 3D structure, which also affects which
other proteins the protein interacts with. Because of this, and because nodes in a proteinprotein
interaction (PPI) network can be represented as protein structure networks (PSNs),
we modeled the integrated PPI and PSN data as a network-of-networks. We found that the
multi-scale network-of-network analysis often resulted in more accurate protein function
prediction than traditional single-scale analysis of PPI data alone or PSN data alone.
Second, the talk will discuss our network-based analyses of protein folding. We had proposed
several approaches for modeling protein 3D structures as PSNs. Static PSNs model the whole,
final 3D structure of a protein. Because the folding of a protein is a dynamic process, where
some parts (3D sub-structures) of a protein fold before others, most recently, we modeled a
protein as a dynamic PSN that captures these sub-structures. We evaluated our PSN models
in the task of protein structural classification. We found that our PSN models outperformed
state-of-the-art approaches for the same task, with dynamic PSNs being superior to static
PSNs.Book of abstracts: 5th Belgrade Bioinformatics Conference, Serbia, Belgrade,17-20 june 2024