A5054675754- Fungal and yeast genetics research
- Prion Diseases and Protein Misfolding
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Genetic Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Heat shock proteins research
- S100 Proteins and Annexins
- Studies on Chitinases and Chitosanases
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Genetic factors in colorectal cancer
- Signaling Pathways in Disease
- Peptidase Inhibition and Analysis
- Microbial Metabolic Engineering and Bioproduction
- Bioinformatics and Genomic Networks
- Cholinesterase and Neurodegenerative Diseases
- Neurological Disorders and Treatments
- Hereditary Neurological Disorders
- Acute Ischemic Stroke Management
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Computational Drug Discovery Methods
- Blood Pressure and Hypertension Studies
St Petersburg University
2015-2025
Umeå University
2021-2024
Amyloidosis Foundation
2016
Emory University
2013
Georgia Institute of Technology
2007-2012
Institute of Experimental Cardiology
2002-2009
In mammalian cells, abnormal proteins that escape proteasome-dependent degradation form small aggregates can be transported into a centrosome-associated structure, called an aggresome. Here we demonstrate in yeast single aggregate formed by the huntingtin exon 1 with expanded polyglutamine domain (103QP) represents bona fide aggresome colocalizes spindle pole body (the centrosome) microtubule-dependent fashion. Since polypeptide lacking proline-rich region (P-region) of (103Q) cannot...
Polyglutamine expansion causes diseases in humans and other mammals. One example is Huntington's disease. Fragments of human huntingtin protein having an expanded polyglutamine stretch form aggregates cause cytotoxicity yeast cells bearing endogenous QN-rich proteins the aggregated (prion) form. Attachment proline(P)-rich region targets polyglutamines to large perinuclear deposit (aggresome). Aggresome formation ameliorates containing only prion Rnq1 protein. Here we show that both with...
The formation of self-perpetuating protein aggregates such as amyloids is associated with various diseases and provides a basis for transmissible (infectious or heritable) isoforms (prions). Many human proteins involved in the regulation transcription contain potentially amyloidogenic regions. Here, it shown that short N-terminal PHC3, component chromatin-modifying complex PRC1 (Polycomb repressive 1), can form prion-like yeast assays, exhibit amyloid properties E. coli-based C-DAG assay,...
Mismatch repair (MMR) is a major DNA pathway in cells from all branches of life that removes replication errors strand-specific manner, such mismatched nucleotides are preferentially removed the newly replicated strand DNA. Here we demonstrate role for MMR helping create new phenotypes nondividing cells. We show mispairs yeast escape during can later be subject to activity strand-independent manner cells, resulting either fully wild-type or mutant sequence. In one case, this responsible what...
DNA mismatch repair greatly increases genome fidelity by recognizing and removing replication errors. In order to understand how this is maintained, it important uncover the relative specificities of different components repair. There are two major mispair recognition complexes in eukaryotes that homologues bacterial MutS proteins, MutSα MutSβ, with base-base mismatches small loop mispairs MutSβ larger mispairs. Upon a mispair, then interact MutL protein. Loops formed on primer strand during...
Pro-inflammatory and amyloidogenic S100A9 protein is central to the amyloid-neuroinflammatory cascade in neurodegenerative diseases. Polyoxometalates (POMs) constitute a diverse group of nanomaterials, which showed potency amyloid inhibition. Here, we have demonstrated that two selected nanosized niobium POMs, Nb10 TiNb9, can act as potent inhibitors assembly. Kinetics analysis based on ThT fluorescence experiments addition either or TiNb9 reduces formation rate quantity. Atomic force...
Age-related macular degeneration (AMD) is a complex disease in which inflammation implicated as key factor but the precise molecular mechanisms are poorly understood. AMD lesions contain an excess of pro-inflammatory S100A9 protein, its retinal significance was yet unexplored. shown to be intrinsically amyloidogenic vitro and vivo. Here, we hypothesized that effects related supramolecular conformation. ARPE-19 cultures were treated with native dimeric fibrillar preparations, cell viability...
We have developed a set of cloning vectors possessing modified Tn903 kanamycin resistance gene that enables the selection both kanamycin-resistant transformants in Escherichia coli and G418-resistant yeasts Saccharomyces cerevisiae, Hansenula polymorpha Pichia pastoris. Expression this yeast is controlled by H. glyceraldehyde-3-phosphate dehydrogenase promoter, while expression E. governed an upstream lacZ promoter. Applicability for disruption S. cerevisiae was demonstrated inactivation...
In yeast, functions of the endoplasmic reticulum (ER) depend on Golgi apparatus Ca2+ pool, which is replenished by medial-Golgi ion pump Pmr1p. Here, to dissect role pool in protein folding and elimination unfolded proteins ER, manifestations pmr1 mutation yeast Hansenula polymorpha were studied. The PMR1 gene was disrupted a H. diploid strain. Haploid segregants this bearing disruption allele viable, though they showed severe growth defect synthetic medium rapidly died during storage at low...
Human urokinase-type plasminogen activator (uPA) is poorly secreted by yeast cells. Here, we have selected Hansenula polymorpha mutants with increased productivity of active extracellular uPA. Several the obtained also demonstrated a defect sorting carboxypeptidase Y to vacuole and mutant loci been identified in six them. All these mutations damaged genes involved protein traffic between Golgi apparatus vacuole, namely PEP3, VPS8, VPS10, VPS17, VPS35. We shown that inactivation VPS10 gene...
Human urokinase-type plasminogen activator (uPA) is poorly secreted and aggregates in the endoplasmic reticulum of yeast cells due to inefficient folding. A screen for Hansenula polymorpha mutants with improved uPA secretion revealed a gene encoding homologue Saccharomyces cerevisiae protein-O-mannosyltransferase Pmt1p. Expression H. PMT1 (HpPMT1) abolished temperature sensitivity S. pmt1 pmt2 double mutant. As cerevisiae, inactivation HpPMT1 affected electrophoretic mobility O-glycosylated...
ABSTRACT In eukaryotic cells, COPI vesicles retrieve resident proteins to the endoplasmic reticulum and mediate intra-Golgi transport. Here, we studied Hansenula polymorpha homologue of Saccharomyces cerevisiae RET1 gene, encoding α-COP, a subunit protein complex. H. ret1 mutants, which expressed truncated α-COP lacking more than 300 C-terminal amino acids, manifested an enhanced ability secrete human urokinase-type plasminogen activator (uPA) inability grow with shortage Ca 2+ ions, whereas...
The amyloid cascade is central for the neurodegeneration disease pathology, including Alzheimer’s and Parkinson’s, remains focus of much current research. S100A9 protein drives amyloid-neuroinflammatory in these diseases. DOPA cyclen-based compounds were used as modifiers inhibitors previously, also a precursor dopamine Parkinson’s treatment. Here, by using fluorescence titration experiments we showed that five selected ligands: DOPA-D-H-DOPA, DOPA-H-H-DOPA, DOPA-D-H, DOPA-cyclen,...