A5001321124- Genetic Neurodegenerative Diseases
- Hereditary Neurological Disorders
- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Genetics and Neurodevelopmental Disorders
- Erythrocyte Function and Pathophysiology
- Immunodeficiency and Autoimmune Disorders
- Neurological diseases and metabolism
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- Growth Hormone and Insulin-like Growth Factors
- Signaling Pathways in Disease
- RNA regulation and disease
- RNA Research and Splicing
- Autophagy in Disease and Therapy
- Metabolism, Diabetes, and Cancer
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Hippo pathway signaling and YAP/TAZ
- Cardiomyopathy and Myosin Studies
Mossakowski Medical Research Institute, Polish Academy of Sciences
2018-2024
Polish Academy of Sciences
2018-2024
Institute of Biochemistry and Biophysics, Polish Academy of Sciences
2015-2019
The rare human disorder chorea-acanthocytosis (ChAc) is caused by mutations in hVPS13A gene. hVps13A protein interacts with actin and regulates the level of phosphatidylinositol 4-phosphate (PI4P) membranes neuronal cells. Yeast Vps13 involved vacuolar transport and, like hVps13A, participates PI4P metabolism. proteins are conserved eukaryotes, but their molecular function remains unknown. One found ChAc patients causes amino acids substitution I2771R which affects localization skeletal...
In 2002 a series of mutations in the GDAP1 gene were reported patients suffering from Charcot‑Marie‑Tooth disease manifesting as early-onset, progressive distal‑muscle wasting and weakness. The molecular etiology ‑GDAP1 has been elucidated but its pathogenesis remains unclear, especially given seemingly contradictory function protein. Expression is observed almost exclusively neuronal cells, however, protein present mitochondria, where it plays role fission, ubiquitous process occurring all...
VPS13 proteins are evolutionarily conserved. Mutations in the four human genes (VPS13A-D) encoding VPS13A-D linked to developmental or neurodegenerative diseases. The relationship between specific localization of individual proteins, their molecular functions, and pathology these diseases is unknown. Here we used a yeast model establish determinants Vps13's interaction with membranes Golgi apparatus. We analyzed different phenotypes arf1-3 arf2Δ vps13∆ strain, reduced activity Arf1 GTPase,...
ABSTRACT Chorea-acanthocytosis (ChAc) is a rare neurodegenerative disease associated with mutations in the human VPS13A gene. The mechanism of ChAc pathogenesis unclear. A simple yeast model was used to investigate function single VSP13 orthologue, Vps13. Vps13, like VPS13A, involved vesicular protein transport, actin cytoskeleton organisation and phospholipid metabolism. newly identified phenotype vps13Δ mutant, sodium dodecyl sulphate (SDS) hypersensitivity, screen genomic library for...
Charcot-Marie-Tooth disease (CMT) is a heritable neurodegenerative that displays great genetic heterogeneity. The genes and mutations underlie this heterogeneity have been extensively characterized by molecular genetics. However, the pathogenesis of vast majority CMT subtypes remains terra incognita. Any attempts to perform experimental therapy for are limited lack understanding at level. In study, we aim identify pathways disturbed in gene encoding GDAP1 using both yeast human cell, based...
The question of whether a newly identified sequence variant is truly causative mutation central problem modern clinical genetics. In the current era massive sequencing, there an urgent need to develop new tools for assessing pathogenic effect variants. Charcot-Marie-Tooth disorders (CMT) with their extreme genetic heterogeneity and relatively homogenous presentation, addressing rare variants within 80 CMT genes extremely challenging. presence multiple single CMT-affected patient makes...
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a heritable neurodegenerative disease characterized by rapid failure within the first months of life and progressive muscle weakness wasting. Although causative gene, IGHMBP2, well defined, information on IGHMBP2 mutations not always sufficient to diagnose particular patients, as gene highly polymorphic pathogenicity many variants unknown. In this study, we generated simple yeast model establish significance for...