PHD Student no. 46/2022/ICHB/PSD

Institute of Bioorganic Chemistry Polish Academy of Sciences, Poland

Updated: 3 months ago
Job Type: FullTime
Deadline: 06 Dec 2022

KEY WORDS: neurodegenerative disease, SCA3, spinocerebellar ataxia 3, ataxin-3, ATXN3, SCA3 mouse, knock-in, mutant protein, PolyQ, CAG repeats, autophagy, proteasome

Research topic: Investigation of a new therapeutic strategy to lower mutant protein in SCA3 / MJD

Principal Investigator: Maciej Figiel

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.

Additional information:

  • Research and doctoral theses shall be carried out within the 2021/41/B/NZ2/03881 project, entitled “Investigation of a new therapeutic strategy to lower mutant protein in SCA3 / MJD” funded by National Science Centre, Poland.
  • PhD students shall receive a stipend in the gross amount of ca 4300 PLN (3800 PLN net), for the period of 36 months with possible extension
  • PhD students shall be subject to social insurance, pursuant to article. 6 section 1 passage 7b of the act of October 13th, 1998 on the social insurance system (Journal of Laws of 2019, item 300, 303 and 730).

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