imagine (Institute of molecular genetics and genetic engineering)
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Multiscale modeling uncovers 7q11.23 copy number variation–dependent changes in ribosomal biogenesis and neuronal maturation and excitability
No full textShort talk: September 13, Fifth Sessio
Establishment of induced pluripotent stem cells derived from patients with 22q11.2 microdeletion as a tool for studying neurodevelopmental disorders
No full textNeurodevelopmental disorders (NDDs), including autism spectrum disorders,
intellectual disability, schizophrenia, and bipolar disorder, present a public health
challenge in modern societies. The prevalence of NDDs is about 10 to 15% of all
births with tendency of increasing worldwide over the last years. On the other hand,
molecular mechanisms underlying NDDs are still unknown. One of the syndromes
with a high risk for NDDs is 22q11.2 Deletion Syndrome (22q11.2DS) caused by
microdeletion 22q11.2, which is the most common microdeletion in humans.
22q11.2DS is one of the strongest known risk factors for development of psychiatric
illness and one of the highest known genetic risks for schizophrenia (approximately
25% of patients with 22q11.2DS develop schizophrenia compared to 1% in the
general population).
Peripheral blood mononuclear cells from both patients with 22q11.2DS and healthy
individuals were reprogrammed using CytoTune™-iPS 2.0 Sendai Reprogramming
Kit. Generated iPSC lines were genotyped in order to identify if any additional
pathogenic CNVs exist. Pluripotency of iPSCs was analyzed by RT-PCR.
Peripheral blood mononuclear cells from five patients with 22q11.2 microdeletion
and three healthy individuals were reprogrammed. Genotyping revealed that some
of the iPSC lines contain additional CNVs. Obtained results revealed that iPSCs
were successfully generated.
Established patient-specific iPSCs provide a platform for studying molecular
mechanisms underlying NDDs.Book of abstracts: Belgrade Neuroscience Next Hub 2024 with international participation 24-25 May 2024. Belgrade, Serbi
Generation of induced pluripotent stem cells from patients with 22q11.2 Duplication Syndrome as an in vitro model system for exploring neurodevelopmental disorders
No full textNeurodevelopmental disorders (NDDs), such as schizophrenia, intellectual
disability, attention-deficit/hyperactivity disorder (ADHD), and autism spectrum
disorders (ASD), arise as a consequence of disruptions in the early development of
the brain. With a prevalence of 10 to 15% of all births and a trend to increase
worldwide, NDDs represent an important public health challenge. Due to
insufficient knowledge of the pathophysiological mechanisms underlying the
development of NDDs, their treatment is primarily focused on the symptoms. The
22q11.2 Duplication Syndrome (22q11.2DupS), caused by microduplication of the
q11.2 region on chromosome 22, is associated with a high risk of developing NDDs,
including ASD, ADHD, developmental delay, and intellectual disability. ASD is
detected in 14-25% of patients with 22q11.2DupS, making it one of the genetic
syndromes with the highest rate of ASD. On the other hand, schizophrenia is less
common in patients with 22q11.2DupS than in the general population, suggesting
that 22q11.2 microduplication could have a protective effect against schizophrenia.
iPSCs were generated by reprogramming peripheral blood mononuclear cells from
patients carrying 22q11.2 microduplication and healthy individuals using
CytoTune™-iPS 2.0 Sendai Reprogramming Kit. Genotyping of iPSC lines was
performed to identify potential additional pathogenic CNVs. Expression of
pluripotency markers was analyzed by RT-PCR.
Induced pluripotent stem cells were generated from three patients with an inherited
form of 22q11.2DupS and their mothers that carry the microdeletion, as well as three
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healthy individuals. Genotyping revealed that some of the iPSC lines contain
additional CNVs. Expression analysis showed that iPSCs were successfully
established.
Generated patient-specific iPSCs carrying 22q11.2 microduplication serve as a
valuable model for gaining insights into the molecular mechanisms underlying
NDDs.Book of abstracts: Belgrade Neuroscience Next Hub 2024 with international participation 24-25 May 2024. Belgrade, Serbi
Biotechnological model for ubiquitous mixed petroleum- and bio-based plastics degradation and upcycling into bacterial nanocellulose
Get PDFUbiquitous post-consumer plastic waste is often physically mixed combining recalcitrant petroleum-based plastics with bioplastics, forming (petro-bio)plastic streams. Finding appropriate end-of-life (EoL) strategies for mixed (petro-bio)plastic waste is highly pertinent in achieving environmental protection, sustainability for plastic value chain industries including recyclers and government policy makers worldwide. The presence of bioplastic mixed in with polyethylene terephthalate (PET) or other petroleum-based plastic streams poses a substantial drawback to mechanical recycling and strongly impedes the development of sustainable EoL routes. Here, we present a model system for the sustainable management of mixed (petro-bio)plastic waste, demonstrating a biotechnological route through synergy-promoted enzymatic degradation of PET–representing petrochemical polyester plastic–mixed with thermoplastic starch (TPS)–as a model bioplastic. Leaf-branch compost cutinase (LCCICCG) and commercial amylase (AMY) deliver effective depolymerization of this mixed (petro-bio)plastic material, with subsequent bio-upcycling of the mixed waste stream into bacterial nanocellulose (BNC) by Komagataeibacter medellinensis. Compared to LCCICCG and AMY, the LCCICCG/AMY combined treatment synergistically produced a 2.6- and 4.4-fold increase in enzymatic decomposition at 70 °C in four days, respectively, yielding sugars and terephthalic acid (TPA) as the main depolymerization building blocks. Bio-upcycling of post-enzymatic degradation hydrolysates resulted in a high BNC yield of 3 g L−1 after 10 days. This work paves the way for sustainable management routes for challenging mixed recalcitrant plastic and bioplastic waste and prepares opportunities for its participation in the circular production of sustainable eco-polymers
IMGGE Annual Research Program 2024
Get PDFDuring 2024, IMGGE researchers will continue exploring following areas:
- human molecular genetics and genomics,
- microbiology and ecology of microorganisms,
- plant molecular biology.
IMGGE researchers will focus on studying molecular mechanisms responsible for the
occurrence of selected rare and non-contagious diseases, as well as on identification of
molecular markers important for diagnosis, prognosis, therapy and prevention. Disease
modeling methodology will be developed using in vitro model systems (2D and 3D primary and
permanent cell lines, induced pluripotent stem cells) and in vivo model systems that include
different animal models. These stydies will aim at discovering the causes of the disease,
identifying new therapeutic targets, testing new therapeutics as well as individual response to
existing therapeutics.
During 2024, the existing IMGGE collection of microorganisms will be further expanded with
new isolates (industrial microorganisms, clinically relevant pathogens, and bacteriophages), and
IMGGI collaborators will devote themselves to studying the antimicrobial and antiviral potential
and application of new isolates, as well as mechanisms of resistance and virulence. The
genomes of selected microorganisms will be sequenced and analyzed to identify new genes of
interest, e.g. producers of bioactive proteins, enzymes and biosynthetic pathways.
Metagenomes of selected environmental or clinical samples will also be sequenced and
analyzed in order to study the biological diversity of complex communities of microorganisms.
When it comes to the molecular biology of plants, the response mechanisms of different model
organisms to abiotic and biotic stress will further be investigated. IMGGE researchers will
analyze the role of different proteins in maintaining cell homeostasis (eg LEA) and genome
stability (Ustilago maydis). The genomes, epigenomes and proteomes of the muscat flower will
be sequenced in order to study the response to stress.Principal Investigator: Dr. Ivana Strahinić, IMGGEDuration period: 202
Gelatin-/Alginate-Based Hydrogel Scaffolds Reinforced with TiO2 Nanoparticles for Simultaneous Release of Allantoin, Caffeic Acid, and Quercetin as Multi-Target Wound Therapy Platform
Get PDFThis study proposes synthesis and evaluation of gelatin-/alginate-based hydrogel scaffolds reinforced with titanium dioxide (TiO2) nanoparticles which, through their combination with allantoin, quercetin, and caffeic acid, provide multi-target therapy directed on all phases of the wound healing process. These scaffolds provide the simultaneous release of bioactive agents and concurrently support cell/tissue repair through the replicated structure of a native extracellular matrix. The hydrogel scaffolds were synthesized via a crosslinking reaction using EDC as a crosslinker for gelatin. Synthesized hydrogel scaffolds and the effect of TiO2 on their properties were characterized by structural, mechanical, morphological, and swelling properties, and the porosity, wettability, adhesion to skin tissue, and simultaneous release features. The biocompatibility of the scaffolds was tested in vitro on fibroblasts (MRC5 cells) and in vivo (Caenorhabditis elegans) in a survival probe. The scaffolds revealed porous interconnected morphology, porosity of 88.33 to 96.76%, elastic modulus of 1.53 to 4.29 MPa, full hydrophilicity, favorable skin adhesivity, and biocompatibility. The simultaneous release was investigated in vitro indicating dependence on the scaffold’s composition and type of bioactive agents. The novel scaffolds designed as multi-target therapy have significant promise for improved wound healing in a beneficial and non-invasive manner
A novel thermostable YtnP lactonase inhibits biofilm formation and induces decomposition of preformed Pseudomonas aeruginosa biofilms
Get PDFBiofilm-associated infections are the main cause of biomaterial implant failure today. The increasing prevalence of antibiotic-resistant pathogens often results in the only solution of implant movement, with serious consequences for patients. Recently, various antimicrobial agents have been recognized as a promising strategy to prevent biofilm formation on implant surfaces. Quorum sensing (QS) plays a central role in the control of bacterial virulence and biofilm formation. The use of quorum quenching (QQ) enzymes to target QS is therefore a promising innovative approach for the development of enzyme-based antivirulence therapeutics, which represent a potential solution to combat infections caused by multidrug-resistant pathogens. This study aimed to characterize the novel YtnP lactonase from the clinical isolate Stenotrophomonas maltophilia 6960 and to investigate its potential to combat the virulence of multidrug-resistant (MDR) Pseudomonas aeruginosa MMA83
AI-Driven Optimization of PCL/PEG Electrospun Scaffolds for Enhanced In Vivo Wound Healing
No full textHere, an artificial intelligence (AI)-based approach was employed to optimize the production of electrospun scaffolds for in vivo wound healing applications. By combining polycaprolactone (PCL) and poly(ethylene glycol) (PEG) in various concentration ratios, dissolved in chloroform (CHCl3) and dimethylformamide (DMF), 125 different polymer combinations were created. From these polymer combinations, electrospun nanofiber meshes were produced and characterized structurally and mechanically via microscopic techniques, including chemical composition and fiber diameter determination. Subsequently, these data were used to train a neural network, creating an AI model to predict the optimal scaffold production solution. Guided by the predictions and experimental outcomes of the AI model, the most promising scaffold for further in vitro analyses was identified. Moreover, we enriched this selected polymer combination by incorporating antibiotics, aiming to develop electrospun nanofiber scaffolds tailored for in vivo wound healing applications. Our study underscores three noteworthy conclusions: (i) the application of AI is pivotal in the fields of material and biomedical sciences, (ii) our methodology provides an effective blueprint for the initial screening of biomedical materials, and (iii) electrospun PCL/PEG antibiotic-bearing scaffolds exhibit outstanding results in promoting neoangiogenesis and facilitating in vivo wound treatment
A genetic screen for blm suppressors in Ustilago maydis identifies novel proteins affecting DNA repair and recombination
No full textThe maintenance of genome integrity is a fundamental cellular process, and it is highly conserved among all domains of life.
Since the DNA molecule is under constant threat from endogenous and exogenous factors that cause its damage, organisms
have evolved several DNA repair mechanisms. Homologous recombination (HR) is essential for the error-free repair of DNA
double-strand breaks, which are the most deleterious lesions. Despite extensive research on HR in different organisms, not only all
functions of known HR factors and interactions among them are still unknown, but the question also arises as to whether there
is a possibility of the existence of unknown factors. The focus of our research is to uncover novel cellular factors that regulate
HR by isolating suppressors of blm in U. maydis, a unicellular phytopathogen that is extremely resistant to radiation and has a
DNA repair system similar to that in humans with highly conserved BRCA2 (named Brh2). We have identified 4 novel factors
of unknown functions (named Rec3, Zdr1, Bls9 and Bls2), and 3 known factors: Rad51, Dna2 and Mph. Mutations in each of
these genes suppress the hydroxyurea sensitivity of blm. Rec3 is a member of the family of Rad51 ATPases. It plays a critical
role in induced allelic recombination and is crucial for the completion of meiosis. We have shown that there is a close functional
connection between Brh2 and Rec3. Zdr1 is Cys2-His2 zinc finger (C2H2-ZF) protein whose loss doesn’t cause a detectable
change in HR, but it is involved in DNA repair. Bls9 doesn’t have any characterised domains. It is involved in DNA repair and HR
between chromosome homologs. Bls2 is an uncharacterized protein that displays a slow-growth phenotype that can be suppressed
by truncated Bls9. These novel factors can provide insights into HR regulation, interactions among HR participants, and relations
to other cellular processes.Book of abstracts: The 52nd EEMGS & 15th ICAW Meeting, Rovinj, Croatia, 23rd - 27th September 202
Genetics of autism
No full textAutizam predstavlja heterogenu grupu neurorazvojnih poremećaja koji karakterišu problemi u
društvenoj interakciji i komunikaciji, kao i prisustvo repetitivnih radnji i stereotipnog ponašanja. Tokom
posljednje tri decenije došlo je do dramatičnog povećanja broja dijagnostikovanih slučajeva. Danas se
smatra da autizam ima više od 2% djece, dominantno dječaka. Rana detekcija ovog poremećaja doprinosi
ranom tretmanu, a samim tim, i boljem ishodu liječenja. Paralelno sa porastom broja oboljelih, raste i
zaisteresovanost javnosti i naučne zajednice za ovaj poremećaj, u prvom redu za njegovu etiologiju. Iako
ona nije velikim dijelom rasvijetljena, pouzdano se zna da autizam ima snažnu i složenu genetsku
komponentu. Zahvaljujući savremenim genetičkim analizama, poput komparativne genomske
hibridizacije i sekvenciranja cijelog egzoma i genoma, genetsku etiologiju autizma je danas moguće
utvrditi kod 30-40% slučajeva. Autizam je dio kliničke slike desetina različitih sindroma, a otkriveno je više
stotina gena koji predstavljaju faktore rizika za njegov nastanak, koji vjerojatno igraju i ključnu ulogu u
modulaciji širokog fenotipskog spektra ovog poremećaja. Sa porastom broja oboljelih raste i broj djece i
članova njihovih porodica koji se u traganju za etiološkom dijagnozom i genetičkim savjetom javljaju u
službe kliničke genetike. Postavljanje precizne dijagnoze genetičkim analizama može modifikovati
terapijski pristup, poboljašavati ishod i omogućiti roditeljima da bolje razumiju bolest i koliki je rizik od
recidiva za porodicu. U ovom članku dat je pregled naučnih saznanja o genetici autizma i aktuelne
smjernice za genetička testiranja ovog poremećaja.Autism represents a heterogeneous group of neurodevelopmental disorders characterised by problems
in social interaction and communication, as well as the presence of repetitive movements and stereotyped
behaviour. During the last three decades, there has been a dramatic increase in the number of diagnosed
cases. Today, it is considered that more than 2% of children, predominantly boys, have autism. Early detection
of this disorder contributes to early treatment and, therefore, to a better treatment outcome. Parallel
to the increase in the number of patients, the interest of the public and the scientific community in
this disorder, primarily in its etiology, is also growing. Although it is not largely illuminated, it is reliably
known that autism has a strong and complex genetic component. Thanks to modern genetic analyses,
such as comparative genomic hybridisation and whole exome and genome sequencing, the genetic etiology
of autism can now be determined in 30-40% of cases. Autism is part of the clinical picture of dozens
of different syndromes, and hundreds of genes have been discovered that represent risk factors for its origin,
which probably play a key role in the modulation of a wide phenotypic spectrum of this disorder. With
an increase in the number of patients, there is a growing number of children and their family members who
come to clinical genetics services in search of etiological diagnosis and genetic counselling. Establishing
a precise diagnosis by genetic analysis can modify the therapeutic approach, improve the outcome and
allow parents to better understand the disease and what the recurrence risk is for the family. This article
provides an overview of scientific knowledge about the genetics of autism and current guidelines for genetic
testing of this disorder