KEY WORDS: neurodegenerative disease, SCA3, spinocerebellar ataxia 3, ataxin-3, ATXN3, SCA3 mouse, knock-in, mutant protein, PolyQ, CAG repeats, autophagy, proteasome
Principal Investigator: Maciej Figiel
Research topic: Investigation of a new therapeutic strategy to lower mutant protein in SCA3 / MJD
I. Project description
Neurodegenerative diseases, including polyglutamine diseases and Alzheimer's disease, are currently incurable. A model disease in this group is spinocerebellar ataxia type 3 (SCA3), which is a genetic neurodegenerative disease caused by a particular type of mutation that results in an increased number of CAG nucleotide repeats in the ATXN3 gene sequence. The mutation in the ATXN3 gene results in the defective protein ataxin-3, which forms toxic aggregates in the cell and also increases the cellular level of beta-amyloid. Ataxin-3 plays a crucial role in controlling which proteins and organelles should be cleared in the cell through two related cellular mechanisms called autophagy and UPS. Ataxin-3 recognizes a protein tag called ubiquitin that directs a protein or cell fragment for breakdown, and detaches this tag from the protein, thereby preventing premature removal of the proteins from the cell. In this project, we will investigate whether forcing the controlled removal of cell fragments by small molecule drugs will repair the disrupted cellular processes resulting from the ATXN3 mutation.
We hope that thanks to this project, we will learn more about the specific role of one of the key pathogenic processes in neurodegenerative diseases related to the dysfunction of protein clearance mechanisms. A detailed study of this mechanism will provide a better understanding of SCA3 and other neurodegenerative diseases, which will enable the design of appropriate treatments.
Postdoc Or Ph D Student In Unfolded Protein Response In Gut Homeostasis, VIB, Belgium, about 3 hours ago
About the lab and the project The VIB Center for Inflammation Research is part of the VIB Life Sciences institute and is connected to Ghent University. Our center focuses on the mechanisms driving...
Ph D Position In Microtubule Targeting Agents In Organoids (1.0 Fte), Utrecht University, Netherlands, 2 days ago
PhD position in Microtubule Targeting Agents in Organoids (1.0 FTE) PhD position in Microtubule Targeting Agents in Organoids (1.0 FTE) Published Deadline Location today 26 Oct Utrecht Join our te...
Ph D Candidate Parkinson’s Disease, Erasmus MC (University Medical Center Rotterdam), Netherlands, 11 days ago
PhD candidate Parkinson’s disease PhD candidate Parkinson’s disease Published Deadline Location yesterday 17 Oct Rotterdam Job description This project will study how genetic variants in the DJ-1 ...
Ph D Position – The Role Of Tick Salivary Proteins In (Auto)Immune Disease, VIB, Belgium, about 3 hours ago
We are interested in the effects of tick derived immunomodulatory proteins on the immune balance and their potential in human disease. This is a joint PhD project between VIB/Hasselt University (B...
Ph D Position In Epigenetics And Gene Regulation (1.0 Fte), Utrecht University, Netherlands, 3 days ago
PhD position in Epigenetics and Gene Regulation (1.0 FTE) PhD position in Epigenetics and Gene Regulation (1.0 FTE) Published Deadline Location today 24 Oct Utrecht Are you interested in mechanism...
Postdoctoral Position In Molecular Biology – University Of Toronto, Canadian Society for Molecular Biosciences CSMB, Canada, about 20 hours ago
The Rhee Lab at the University of Toronto Mississauga has one or two postdoctoral positions available for candidates with expertise in molecular biology, cell biology, or related biological areas....