This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie COFUND grant agreement No 665735.

Bio4Med Research Projects:


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11: Bio4Med - Involvement of novel Hsp90 co-chaperones, Sgt1 and CHP-1, in Parkinson’s disease

Supervisor:
prof. Anna Filipek
Foreign partner:
Prof. Serge Weis, Neurosychiatric Hospital Wagner-Jauregg, Linz, Austria
WWW
http://en.nencki.gov.pl/laboratory-of-calcium-binding-proteins
Background:
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the accumulation of Lewy bodies within neurons of substantia nigra. Lewy bodies, composed of alpha-synuclein, are the pathological hallmark of this disorder and the cascade that allows alpha-synuclein to misfold, aggregate and form these inclusions has been extensively studied. Many other proteins, including chaperones such as Hsp90, have been found to co-localize with Lewy bodies. Some studies have revealed that Hsp90 prevents alpha-synuclein aggregation and forms a complex with the transiently populated toxic oligomeric alpha-synuclein species. The function of Hsp90 is regulated by different co-chaperones, the list of which is still open. Quite recently, it has been shown that the Sgt1 and CHP-1 proteins are novel co-chaperones of Hsp90 (Zabka et al., 2008, Michowski et al., 2010). Both these proteins are present in mammalian brain, however, their function in the brain has not been, up to now, studied extensively. There is only one report showing changes in the level of Sgt1 in brain neurons of Alzheimer disease patients (Spiechowicz et al., 2006).
Aim:
Thus, the aim of this project is to examine the function of the novel Hsp90 co-chaperones, Sgt1 and CHP-1, in PD. Mainly, the level as well as cellular and subcellular localization of these two co-chaperones and of Hsp90 will be analyzed in brain slices derived from a mouse model of PD. In addition, the influence of Sgt1 and CHP-1 on Hsp90-dependent alpha-synuclein aggregation will be analyzed by applying in vitro assays such as transmission electron microscopy, size exclusion chromatography, isothermal titration, aggregation and cytotoxicity assays.
Requirements:
Interest in protein biochemistry, molecular biology and cell biology. Basic knowledge of protein purification methods, SDS-PAGE, western blotting, plasmid construction, cell culture and transfection. The candidate should also be prepared for the work with animals. In general, we will welcome a diligent, dedicated and communicative person with an ability to work in a team and with a very good knowledge of English. Candidates must not have resided or carried out their main activity (work, studies, etc.) in Poland for more than 12 months in the past 3 years.