Stockholm university

Research group Group Andréasson

We study how cells safeguard health and aging by maintaining their proteomes functional. Our research develops fundamental insight into the mechanisms of the proteostasis system.

Group description

We study how cells maintain their proteomes functional with the help of the proteostasis system to ensure health and aging. Our projects develop insight into the mechanisms of the proteostasis system, including chaperone-assisted protein folding at the ribosome, protein quality control (UPS and autophagy) and transcriptional stress responses (Hsf1). The experimental approaches integrate genetics, biochemistry and cell biology and we employ budding yeast (Saccharomyces cerevisiae) and mammalian cell culture as models.

The proteostasis system is burdened by mistakes during protein biosynthesis as well as by structural damage caused by intrinsic and environmental stressors. This endangers the health of the organism by accelerating the production of toxic misfolded and aggregating proteins.

Protein aggregates are linked to disease progression and are found in the brains of individuals with neurodegenerative disease, e.g. Alzheimer’s and Parkinson’s. Furthermore, cancer cells with its high growth rates, genetic instability and stressful tumor environments accumulate misfolded and aggregated proteins. The age-related decline of physiology is also associated with protein misfolding suggesting a connection between age-induced decline and impairment of the proteostasis system.

Understanding the molecular mechanisms that counter-balance proteostasis damage is a fundamental scientific challenge and is crucial for the development of new strategies to combat disease and aging. We work to unravel these mechanisms.

Current projects aim at providing insight into the setup of the proteostasis system at the molecular level. We combine methods from molecular biology, biochemistry, genetics and cell biology. Concepts are developed in the model eukaryote budding yeast (Saccharomyces cerevisiae) and tested in human system using biochemistry and cell culture.

  • Chaperone discovery

We are expanding the known proteostasis system by exploring new putative chaperones starting with the yeast model. Characterization unravels how these orphan molecular chaperones function on the biochemical level as well as their role and interactions within the cellular proteostasis system.

  • Protein quality control

The research group has a long-standing interest in the mechanisms of protein quality control, i.e. how the cell ensures removal of toxic misfolded proteins. We mainly focus on developing insight into the function of molecular chaperones Hsp70 and Hsp104 and how they participate in protein quality control, including removal by refolding (disaggregation) and degradation (UPS and autophagy) of the misfolded and aggregated proteins.

  • Stress transcription by Hsf1

Cells respond to the accumulation of misfolded proteins by activating ancient stress-responsive transcriptional programs. This includes the transcriptional activator Heat-shock Factor 1 (Hsf1). We are deciphering how the transcriptional activity of Hsf1 is controlled by misfolded proteins and chaperones in yeast and human cells.
 

Group members

Group managers

Claes Andreasson

University Lecturer

Department of Molecular Biosciences, The Wenner-Gren Institute
Claes Andréasson

Members

Andrea Lobo Municio

PhD student

Department of Molecular Biosciences, The Wenner-Gren Institute

Jany Quintana Cordero

PhD student

Department of Molecular Biosciences, The Wenner-Gren Institute

Magdalena Marchewa

Student

Department of Molecular Biosciences, The Wenner-Gren Institute

Michela Ciccarelli

PhD student

Department of Molecular Biosciences, The Wenner-Gren Institute
Michela Ciccarelli

Mihaela Pravica

Guest PhD student

Department of Molecular Biosciences, The Wenner-Gren Institute

Pasquale Sileo

Postdoc

Department of Molecular Biosciences, The Wenner-Gren Institute
Pasquale Sileo

Terence Infant Wilson Lawrence

PhD student

Department of Molecular Biosciences, The Wenner-Gren Institute
Terence Infant Lawrence Wilson

Publications