Research is primarily focused on understanding how eukaryotic cells maintain their proteins folded and functional by mechanistic studies of the cellular protein homeostasis (proteostasis) system.
Breakdown of the proteostasis system has severe consequences for the organism and results in the accumulation of toxic misfolded and aggregated proteins. Strikingly, protein aggregates are found in the brains of individuals with neurodegenerative disease, e.g. Alzheimer’s and Parkinson’s and is linked to disease progression. 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 linked to protein misfolding suggesting a connection between age-induced decline and impairment of the proteostasis system. Understanding the molecular mechanisms that maintain cellular proteins folded and functional is a fundamental challenge in the biological sciences and is crucial for the development of new strategies to combat disease and aging.
On-going projects
Current projects aim at providing insight 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 on human proteins and in cell culture.
Chaperone discovery
We aim at finding novel factors that act to chaperone the folding of newly produced proteins at the ribosome. 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 understanding how the molecular chaperones Hsp70 and Hsp104 are involved in protein quality control of misfolded proteins, including removal by refolding and degradation of the misfolded protein.
Stress transcription by Hsf1
Cells respond to the build-up of misfolded proteins by activating stress-responsive transcriptional programs. This includes the ancient transcription factor 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.
Selected publications
Masser AE, Ciccarelli M, Andréasson C. (2020) Hsf1 on a leash - controlling the heat shock response by chaperone titration. Exp Cell Res. Nov 1;396(1):112246. doi: 10.1016/j.yexcr.2020.112246.
Kohler V, Andréasson C. (2020) Hsp70-mediated quality control: should I stay or should I go? Biol Chem. Oct 25;401(11):1233-1248. doi: 10.1515/hsz-2020-0187.
Masser AE, Kang W, Roy J, Kaimal JM, Quintana-Cordero J, Friedländer MR, Andréasson C. (2019) Cytoplasmic protein misfolding titrates Hsp70 to activate nuclear Hsf1. Elife. Sep 25;8:e47791. doi: 10.7554/eLife.47791.
Andréasson C, Ott M, Büttner S. (2019) Mitochondria orchestrate proteostatic and metabolic stress responses. EMBO Rep. 2019 Oct 4;20(10):e47865. doi: 10.15252/embr.201947865.
Suhm T, Kaimal JM, Dawitz H, Peselj C, Masser AE, Hanzén S, Ambrožič M, Smialowska A, Björck ML, Brzezinski P, Nyström T, Büttner S, Andréasson C, Ott M. (2018) Mitochondrial Translation Efficiency Controls Cytoplasmic Protein Homeostasis. Cell Metab. 2018 Jun 5;27(6):1309-1322.e6. doi: 10.1016/j.cmet.2018.04.011.
Kandasamy G, Andréasson C. (2018) Hsp70-Hsp110 chaperones deliver ubiquitin dependent and independent substrates to the 26S proteasome for proteolysis. J Cell Sci Mar 5. pii: jcs.210948. doi: 10.1242/jcs.210948.
Gowda NKC, Kaimal JM, Kityk R, Daniel C, Liebau J, Öhman M, Mayer MP, Andréasson C. (2018) Nucleotide exchange factors Fes1 and HspBP1 mimic substrate to release misfolded proteins from Hsp70. Nat Struct Mol Biol. Jan;25(1):83-89.
Kaimal JM, Kandasamy G, Gasser F, Andréasson C. (2017) Coordinated Hsp110 and Hsp104 Activities Power Protein Disaggregation in Saccharomyces cerevisiae. Mol Cell Biol. May 16;37(11)
Gowda NK, Kaimal JM, Masser AE, Kang W, Friedländer MR, Andréasson C. (2016) Cytosolic splice isoform of Hsp70 nucleotide exchange factor Fes1 is required for the degradation of misfolded proteins in yeast. Mol Biol Cell. Apr 15;27(8):1210-9
