Ilya Mazunin

Ilya Mazunin
Skolkovo Institute of Science and Technology | Skoltech · Center for Molecular and Cellular Biology

PhD

About

58
Publications
11,294
Reads
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424
Citations
Additional affiliations
November 2019 - present
Skolkovo Institute of Science and Technology
Position
  • Senior Researcher
September 2011 - present
School of Life Sciences
Position
  • Professor (Assistant)
Description
  • Molecular biology Genome engineering Synthetic biology
May 2011 - December 2018
School of Life Sciences
Position
  • Principal Investigator
Education
September 2006 - September 2009
September 2001 - September 2005
Chelyabinsk State University
Field of study
  • Genetics

Publications

Publications (58)
Article
Full-text available
Genome editing technologies became tremendously useful in laboratories around the world. ZFN and TALENs were successfully adapted for production specific doublestranded breaks in mtDNA. Recently developed more efficient and universal CRISPR\Cas9 based technology is still in the very beginning for its adaptation for mtDNA editing. In this article, w...
Article
Full-text available
Mutations in mitochondrial DNA (mtDNA) may result in various pathological processes. Detection of mutant mtDNAs is a problem for diagnostic practice that is complicated by heteroplasmy – a phenomenon of the inferring presence of at least two allelic variants of the mitochondrial genome. Also, the level of heteroplasmy largely determines the profile...
Article
Full-text available
Mitochondria possess their own genome that, despite its small size, is critically important for their functioning, as it encodes several dozens of RNAs and proteins. All biochemical processes typical for bacterial and nuclear DNA are described in mitochondrial matrix: replication, repair, recombination, and transcription. Commonly, their mechanisms...
Article
Full-text available
Apart from the nucleus, the mitochondrion is the only organelle of an animal cell that contains its own genome. Mitochondrial DNA is much less in size than the nuclear one and codes for only several dozens of biological macromolecules. Nevertheless, mutations in mitochondrial genes often result in the occurrence of serious hereditary neuromuscular...
Article
Full-text available
ATP and other metabolites, which are necessary for the development, maintenance, and functioning of bodily cells are all synthesized in the mitochondria. Multiple copies of the genome, present within the mitochondria, together with its maternal inheritance, determine the clinical manifestation and spreading of mutations in mitochondrial DNA (mtDNA)...
Article
The mutational spectrum of the mitochondrial DNA (mtDNA) does not resemble any of the known mutational signatures of the nuclear genome and variation in mtDNA mutational spectra between different organisms is still incomprehensible. Since mitochondria are responsible for aerobic respiration, it is expected that mtDNA mutational spectrum is affected...
Article
Full-text available
Type V Cas12a nucleases are DNA editors working in a wide temperature range and using expanded protospacer-adjacent motifs (PAMs). Though they are widely used, there is still a demand for discovering new ones. Here, we demonstrate a novel ortholog from Ruminococcus bromii sp. entitled RbCas12a, which is able to efficiently cleave target DNA templat...
Article
Full-text available
Congenital myasthenic syndrome (CMS) is a neuromuscular disorder caused by pathogenic variants in several genes encoding junction proteins. One of these genes is CHAT which encodes choline acetyltransferase. Here, we report a family with compound heterozygote CHAT disease-causing mutations. The c.1061C>T (p.Thr354Met) mutation has been known previo...
Preprint
Full-text available
The mutational spectrum of the mitochondrial DNA (mtDNA) does not resemble any of the known mutational signatures of the nuclear genome and variation in mtDNA mutational spectra between different tissues and organisms is still incomprehensible. Since mitochondria is tightly involved in aerobic energy production, it is expected that mtDNA mutational...
Article
Full-text available
CRISPR RNAs (crRNAs) directing target DNA cleavage by Type V-A Cas12a nucleases consist of constant repeat-derived 5'-scaffold moiety and variable 3'-spacer moieties. Here, we demonstrate that removal of most of the 20-nucleotide scaffold has only a slight effect on in vitro target DNA cleavage by a Cas12a ortholog from Acidaminococcus sp. (AsCas12...
Article
Full-text available
With the nucleus as an exception, mitochondria are the only animal cell organelles containing their own genetic information, called mitochondrial DNA (mtDNA). During oocyte maturation, the mtDNA copy number dramatically increases and the distribution of mitochondria changes significantly. As oocyte maturation requires a large amount of ATP for cont...
Conference Paper
Full-text available
Most pathogenic mitochondrial DNA (mtDNA) mutations are commonly heteroplasmic, whereby wild type and mutant genomes coexist in the same organelle. An increase in the number of mutant molecules can lead to the reaching of a certain threshold of heteroplasmy and the manifestation of mitochondrial disease. We propose a strategy for modifying the comp...
Article
Full-text available
The generally accepted theory of the genetic drift of mitochondrial alleles during mammalian ontogenesis is based on the presence of a selective bottleneck in the female germline. However, there is a variety of different theories on the pathways of genetic regulation of mitochondrial DNA (mtDNA) dynamics in oogenesis and adult somatic cells. The cu...
Article
Epiphyseal chondrodysplasia, Miura type (ECDM) is a skeletal dysplasia with tall stature and distinctive skeletal features caused by heterozygous NPR2 pathogenic variants. Only four families have been reported. We present a family with five affected individuals (mother, three sons, and daughter). The mother's phenotype was relatively mild: borderli...
Article
Full-text available
It has long been known that defects in the structure of the mitochondrial genome can cause various neuromuscular and neurodegenerative diseases. Nevertheless, at present there is no effective method for treating mitochondrial diseases. The major problem with the treatment of such diseases is associated with mitochondrial DNA (mtDNA) heteroplasmy. I...
Preprint
Full-text available
Mitochondrial mutational signature is very conserved and low deviations between species have been associated with longevity. By reconstructing species-specific mtDNA mutational spectrum for ray-finned fishes (Actinopterygii), we observed that temperature is a strong additional factor shaping the mtDNA mutational spectrum in ectotherms. The analysis...
Preprint
Full-text available
Ageing is associated with accumulation of somatic mutations. This process is especially pronounced in mitochondrial genomes (mtDNA) of postmitotic cells, where the accumulation of somatic mitochondrial deletions is associated with healthy ageing and mitochondrial encephalomyopathies. Deletions are often flanked by direct nucleotide repeats, however...
Article
Full-text available
Currently, the mitochondrial component is becoming increasingly significant in the development and progression of glaucoma optic neuropathy. Since mitochondria have their own genetic apparatus, the study of qualitative and quantitative changes in mitochondrial DNA (mtDNA) becomes part of the disease diagnosis, in addition to studying the functional...
Article
Full-text available
Our data first represent the variety of Leber's hereditary optic neuropathy (LHON) mutations in Western Siberia. LHON is a disorder caused by pathogenic mutations in the mitochondrial DNA (mtDNA), inherited maternally and presents mainly in young adults, predominantly males. Clinically, LHON manifests itself as painless central vision loss, resulti...
Article
Full-text available
Gypsy moth Lymantria dispar L. 1758 (Lepidoptera: Erebidae) is one of the most dangerous forest pests of the Holarctic region. Outbreaks of gypsy moth populations lead to significant defoliation of local forests. Within the vast territory of the West Siberian Plain, we noted the outbreak front movement in the north-east direction with a speed 100-2...
Article
Full-text available
Mitochondrial DNA (mtDNA) encodes core subunits of oxidative phosphorylation complexes and, as a result of intricate regulatory crosstalk between nuclear and mitochondrial genomes, the total number of mtDNA copies fits the requirements of each cell type. Deviations from the physiological number of mtDNA copies are expected to be deleterious and mig...
Preprint
Full-text available
It has been shown recently that mitochondrial (mtDNA) somatic variants are numerous enough to trace cellular lineages in our body. Here we extend this statement and demonstrate that mtDNA variants can be interpreted not only as neutral markers of cell divisions but the relative frequency of different mtDNA substitutions (i.e. mtDNA mutational spect...
Article
Full-text available
Background Inflammatory response plays a key role in the development of insulin resistance (IR) in obesity. Oxidative stress triggers the replication of the mitochondrial genome and division of the organelle. The purpose of this study was to identify the relationship of chemerin and TNF-α with mitochondrial DNA (mtDNA) copy number in subcutaneous a...
Article
Full-text available
Background Mitochondria play a central role in the regulation of energy metabolism, and the biogenesis of mitochondria is enhanced by the action of nitric oxide (NO), which is the key signaling molecule in the regulation of vascular homeostasis. A disturbance in the regulation of energy metabolism can be a key reason for the formation of insulin re...
Article
Full-text available
Many mitochondrial genes have been transferred to the nucleus in course of evolution. The products of expression of these genes, being still necessary for organelle function, are imported there from the cytosol. Molecular mechanisms of protein import are studied much deeper than those of nucleic acids. The latter, it seems to us, retards the develo...
Article
Full-text available
Background Maternally inherited Wolbachia symbionts infect D. melanogaster populations worldwide. Infection rates vary greatly. Genetic diversity of Wolbachia in D. melanogaster can be subdivided into several closely related genotypes coinherited with certain mtDNA lineages. mtDNA haplotypes have the following global distribution pattern: mtDNA cla...
Article
Full-text available
Pathogenic mitochondrial DNA (mtDNA) mutations are often in a state of heteroplasmy. The increasing mtDNA mutation load with age generally related to aggravation of symptoms and is also one of the main sign of organism ageing. Heteroplasmy shifting which can alleviate mitochondrial functionality is the most perspective approach to fight mitochondri...
Conference Paper
Full-text available
Nuclear genome size (nucDNA) is higher in long-lived chordata species, where selection against expansion of selfish elements is relaxed due to: (i) lower effective population size (Ne), (ii) higher cell volume, (iii) extended cell cycle period, etc. Mitochondrial genome (mtDNA) has one more, intracellular level of selection, which might change evol...
Poster
Full-text available
RGEN/Cpf1 is a gene editing system for AT-rich sequences, which generates staggered ends in its PAM-distal target site. This system, which in its RNA part recognizes a DNA target site through Watson-Crick interactions, has not been applied to mtDNA yet. We expected that both RNA and protein parts of the system require modifications for its effectiv...
Poster
Full-text available
Cas9-BE4-GAM and Cas9-ABE 7.10 nucleases were cloned into a vector containing the mitochondrial targeting signal from the subunit VIIIA of cytochrome c-oxidase (COX8A MTS) and 3xFLAG for visualization intracellular protein localization. For fluorescence lifetime imaging from the 3’ end in ORF with the base editing proteins TurboGFP gene is located...
Article
Full-text available
Many mitochondrial genes have been transferred to nucleus in course of evolution. The products of these genes expression, being still necessary for organelle function, are imported there from cytosol. Molecular mechanisms of protein import are studied much deeper than that for nucleic acids. The latter, as it seems to us, retards the development of...
Conference Paper
Full-text available
Article
Full-text available
Mitochondrial DNA encodes core subunits of oxidative phosphorylation complex, and as a result of a complex regulatory crosstalk between nuclear and mitochondrial genomes the total number of mtDNA copies fits the requirements of each cell type. Deviations from the optimal number of mtDNA copies are expected to be deleterious and thus can cause some...
Article
Full-text available
The development of the metabolic syndrome (MS) involves many genes. Certain evidence exists in the literature on the association of polymorphism in the mitochondrial DNA (mtDNA) oriB site, also known as the polycytosine pathway, with the development of insulin resistance, type 2 diabetes mellitus (T2DM) and other metabolic disorders in various ethn...
Article
Full-text available
Leber hereditary optic neuropathy is characterized by bilateral, painless loss of vision in children and young adults (generally up to 25 years old). Since its first description in 1871, the understanding of its etiology and pathogenesis has improved considerably. The article considers Leber neuropathy from the points of view of ophthalmology, neur...
Article
Full-text available
Different genes are involved in the development of pathology and formation the metabolic syndrome (MS) phenotype. In the literature, there is a data connection to the site oriB polymorphisms of mitochondrial DNA (mtDNA), known as 16184-16193 polycytosine tract, with insulin resistance, type 2 diabetes (T2DM) and other metabolic abnormalities in dif...
Poster
Full-text available
Motivation and Aim: A significant barrier to new insights in mitochondrial biology and clinical applications for mtDNA disorders is our general inability to manipulate the mtDNA sequence. The CRISPR/Cas9 system uses a specific sgRNA to direct a Cas9 nuclease to the target DNA site, where it induces a double-stranded DNA break. This system has not b...
Poster
Full-text available
Numerous works describe correlations between mitochondrial DNA (mtDNA) properties and species-specific life-history traits: GC content increases with species longevity and decreases with basal metabolic rate; abundance of direct, inverted and complementary repeats decreases with maximal lifespan; mtDNA length decreases with mammalian body mass but...
Article
Full-text available
A strain of a hyperthermophilic filamentous archaeon was isolated from a sample of Kamchatka hot spring sediment. Isolate 1807-2 grew optimally at 85 °C, pH 6.0-6.5, the parameters being close to those at the sampling site. 16S rRNA gene sequence analysis placed the novel isolate in the crenarchaeal genus Thermofilum; Thermofilum pendens was its cl...
Article
Full-text available
The research objective is to establish the link between heat shock protein 27 and ubiquitin mRNA expression as well as Jukart tumor cell apoptosis.The method of flow cytofluorometry has been used to evaluate apoptosis realization using FITC-labeled annexin V and propidium iodide along with the amount of reactive oxygen species. Spectrofluorimetry h...
Article
Full-text available
Mitochondria are key cellular organelles responsible for many different functions. The molecular biology of mitochondria is continuously subject to comprehensive studies. However, detailed mechanisms of mitochondrial biogenesis are still unclear. Fusion and fission are among the most enigmatic processes connected with mitochondria. On the other han...
Article
Full-text available
Opposite effects of common γ-chain cytokines (IL-2, IL-7, and IL-15) on the expression of Gfi1 and U2af1l4 genes regulating alternative splicing of Ptprc gene in T cells at different stages of differentiation were demonstrated in vitro. Generally, produced a dose-dependent activating effect on T cells, while to the effects of rIL-7 and rIL-15 on T...
Article
Full-text available
Metabolic syndrome is a complex of metabolic, hormonal, and clinical disorders. Defects in mitochondrial functions play an important role in the metabolic syndrome pathogenesis. Here, variations in the number of mitochondrial DNA (mtDNA) copies were evaluated in different fat-tissue and peripheral-blood-leukocyte samples from metabolic syndrome pat...
Article
Full-text available
In this review we discuss the molecular mechanisms of insulin resistance concomitant with metabolic inflammation. We also analyze the world results of experimental and clinical studies which aimed at identifying the molecular targets for the development of new prevention and treatment of insulin resistance.
Article
Full-text available
Alternative splicing of Ptprc gene is a key event in memory T cell differentiation. This gene encodes transmembrane tyrosine phosphatase CD45. One of potential mechanisms of alternative splicing regulation is based on antagonistic effects of auxiliary splicing factor U2AF26 and transcription factor Gfi1. These two proteins regulate antigen-dependen...
Article
Full-text available
The alternative splicing of the Ptprc gene is a key event in memory T-cell differentiation. This gene encodes a transmembrane tyrosine phosphatase CD45. One of the potential mechanisms of alternative splicing regulation is based on the antagonistic effects of a U2AF26 auxiliary splicing factor and Gfi1 transcription factor. These two proteins regul...
Article
Full-text available
To fill remaining gaps in mitochondrial DNA diversity in the least surveyed eastern and western flanks of Siberia, 391 mtDNA samples (144 Tubalar from Altai, 87 Even from northeastern Siberia, and 160 Ulchi from the Russian Far East) were characterized via high-resolution restriction fragment length polymorphism/single nucleotide polymorphisms anal...
Article
Full-text available
Through extended survey of mitochondrial DNA (mtDNA) diversity in the Nganasan, Yukaghir, Chuvantsi, Chukchi, Siberian Eskimos, and Commander Aleuts, we filled important gaps in previously unidentified internal sequence variation within haplogroups A, C, and D, three of five (A-D and X) canonical mtDNA lineages that defined Pleistocenic extension f...

Projects

Projects (6)
Project
Diagnosis and management of hereditary disorders
Project
Metagenomic data analysis to discover novel proteins for efficient genome editing
Project
Influence of mitochondrial DNA qualitative and quantitative characteristics on the success of fertilization and subsequent development of the human embryo