Inflammatory Signalling Lab

Inflammatory Signalling Lab

Group leader
Annika Meinander, Docent, PhD
Academy of Finland Research Fellow 1.9.2914-31.8.2019
Senior Lecturer (Akademilektor)
Cell Biology

Group Members
Anna Aalto, PhD student
Aravind Kumar Mohan, PhD student
Christa Kietz, PhD student
Douglas Richmond, PhD student

Vilma Pollari, MSc student
Fanny Sundqvist, MSc student
Sabrina Benoit, MSc student
Shamima Afrin Ruma, MSc student

Contact information

Faculty of Science and Engineering
Cell Biology
BioCity, 2 nd floor
Tykistokatu 6
FI-20520 Turku
Finland
Tel. +358 469201699
Tel. internal 215 4602
Email: annika.meinander @ abo.fi

 

Description of Project

Regulation of inflammatory signalling by ubiquitination

Proper regulation of inflammatory responses is important to avoid development of diseases such as chronic inflammation and cancer. To be able to control unwanted inflammation, flexible but precise mechanisms are required to tune inflammatory signals in the cells. To find molecular switches that may be used to target inflammatory signalling, we aim at understanding how inflammation is regulated in cells at the molecular level. A major regulator of inflammation is the NF-κB family of transcription factors, and these factors are chronically active in many inflammatory diseases. Post-translational modifications such as ubiquitination increase the possibilities to regulate protein functions, and my laboratory studies how signalling mediated via ubiquitination regulates the NF-κB signalling pathways. As regulation of inflammation is very complicated in mammalian cells, we use the fruit fly Drosophila melanogaster as a model organism. The signalling mechanisms controlling as well ubiquitination as NF-κB responses are well conserved between mammals and flies, hence, Drosophila serves as an excellent model organism to study the basic principles of this inflammation-promoting signalling pathway.

As ubiquitination is a post-translational modification that is induced and removed in a regulated, flexible manner, it may be used as a drug target for tuning inflammatory signalling. To be able to target ubiquitination, we will investigate how ubiquitination patterns are changed during inflammation. Further, we aim to find regulators of ubiquitination as well as to determine executors of ubiquitin signalling in the NF-κB pathways. Pinpointing the changes in ubiquitination during inflammation may also allow us to develop new diagnostic markers for inflammation. As intestinal inflammation is a specific interest of ours, and as the Drosophila intestine is a recognised and convenient model for intestinal disease, we are particularly interested in targeting ubiquitination events in intestinal inflammation.

 

Ongoing Projects

Characterisation of M1-linked ubiquitination in inflammatory signalling in Drosophila

Regulation of NF-κB signalling by ubiquitination

Caspase-mediated regulation of ubiquitination in inflammatory signalling in Drosophila

Intermediate filament networks in Drosophila epithelial tissues

 

Funding

The Academy of Finland
The Sigrid Jusélius Foundation
The Magnus Ehrnrooth Foundation
The Liv och Hälsa Foundation
The Doctoral Network of Molecular Biosciences (MolBio)

 

List of publications

Kietz C, Pollari V, Meinander A. (2018) Generating Germ-Free Drosophila toStudy Gut-Microbe Interactions: Protocol to Rear Drosophila under Axenic Condition. Curr Protoc Toxicol, In press

Gullmets J, Torvaldson E, Lindqvist J, Imanishi SY, Taimen P, Meinander A*, Eriksson JE*. (2017) Internal epithelia in Drosophila display rudimentary competence to form cytoplasmic networks of transgenic human vimentin. FASEB J. doi:10.1096, *equal contribution

Sahlgren C, Meinander A, Zhang H, Cheng F, Preis M, Xu C, Salminen TA, Toivola D, Abankwa D, Rosling A, Karaman DŞ, Salo-Ahen OMH, Österbacka R, Eriksson JE, Willför S, Petre I, Peltonen J, Leino R, Johnson M, Rosenholm J, Sandler N. (2017) Tailored Approaches in Drug Development and Diagnostics: From Molecular Design to Biological Model Systems. Adv. Healthc. Mater. doi: 10.1002

Meinander A, Runchel C, Tenev T, Chen L, Kim C-H, Ribeiro PS, Broemer M, Leulier F, Zvelebil M, Silverman N and Meier P. (2012) Ubiquitylation of the Initiator Caspase Dredd is Required for Innate Immune Signalling.  EMBO J. 31: 2770-2783.

Toivonen HT, Meinander A, Asaoka T, Westerlund M, Pettersson F, Mikhailov A, Eriksson JE, and Saxén H. (2011) Modeling reveals that dynamic regulation of c-FLIP levels determines cell-to-cell distribution of CD95-mediated apoptosis. J. Biol. Chem. 286: 18375-18382.

Petre I, Mizera A, Hyder CL, Meinander A, Mikhailov A, Morimoto RI, Eriksson JE, Sistonen L, Morimoto RI, and Back R-J. (2011) A simple mass action model for the eukaryotic heat shock response and its mathematical validation. J. Natural Computing 10: 595-612.

Blom T, Bergelin N, Meinander A, Löf C, Slotte JP, Eriksson JE, and Törnquist K. (2010) An autocrine sphingosine-1-phosphate signaling loop enhances NF-κB-activation and survival. BMC Cell Biology 11: 45 .

Kaunisto A, Kochin V, Asaoka T, Mikhailov A, Poukkula M, Meinander A, and Eriksson JE. (2009) PKC-mediated phosphorylation regulates c-FLIP ubiquitylation and stability. Cell Death Differ. 16: 1215-1226.

Rosenholm JM, Meinander A, Peuhu E, Niemi R, Eriksson JE, Sahlgren CM, and Lindén M. (2009) Targeting of porous hybrid silica nanoparticles to cancer cells. ACS Nano. 3: 197-206.

Elphick LM, Hawat M, Toms NJ, Meinander A, Mikhailov A, Eriksson JE, and Kass GEN. (2008) Opposing roles for caspase and calpain death proteases in L-glutamate-induced oxidative neurotoxicity. Toxicol. Appl. Pharmacol. 232: 258-267.

Meinander A, Söderström TS, Kaunisto A, Poukkula M, Sistonen L, and Eriksson JE. (2007) Fever-like hyperthermia controls T-lymphocyte persistence by inducing degradation of c-FLIPshort. J. Immunol. 178: 3944-3953.

Elphick LM, Meinander A, Mikhailov A, Richard M, Toms, NJ, Eriksson JE, and Kass GEN. (2006) Live cell detection of caspase-3 activation by a Discosoma-red-fluorescent-protein-based fluorescence resonance energy transfer construct. Anal. Biochem. 349: 148-155.

Tran SEF, Meinander A, and Eriksson JE. (2004) Instant decisions: transcription-independent control of death receptor-mediated apoptosis. Trends Biochem. Sci. 11: 601-606.

Tran SEF, Meinander A, Holmström TH, Riviero-Muller A, Heiskanen KM, Linnau EK, Courtney MJ, Mosser DD, Sistonen L, and Eriksson JE. (2003) Heat stress downregulates FLIP and sensitizes cells to Fas receptor-mediated apoptosis. Cell Death Differ. 10: 1137-1147.

Härmälä-Braskén AS, Mikhailov A, Söderström T, Meinander A, Holmström TH, Damuni Z, and Eriksson JE. (2003) Suppression of TNF-a, TRAIL and Fas-receptor induced apoptosis by inhibition of type-2A protein phosphatase activity. Oncogene 22: 7677-86.

Holmberg CI, Hietakangas V, Mikhailov A, Rantanen JO, Kallio M, Meinander A, Hellman J, Morrice N, MacKintosh C, Morimoto RI, Eriksson JE, and Sistonen L. (2001) Phosphorylation of serine 230 promotes inducible transcriptional activity of heat shock factor 1. EMBO J. 20: 3800-3810.

Uppdaterad 5.4.2018