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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

Fanny Sundqvist, MSc student
Sabrina Benoit, MSc student

Contact information

Faculty of Science and Engineering
Cell Biology
BioCity, 2nd 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

Targeting ubiquitin signalling in chronic inflammation

Targeting chronic intestinal inflammation by interfering with ubiquitin signaling

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)

 

Selected publications

Aalto A, Mohan AK, Schwintzer L, Kupka S, Walczak H, Broemer M, Meinander A. (2018) M1-linked ubiquitination by LUBEL is required for inflammatory responses to oral infection in Drosophila. Cell Death Differ. Ahead of print, doi: 10.1038/s41418-018-0164-x

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, Ahead of print, doi: 10.1002/cptx.52

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.

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.

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.

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

Uppdaterad 5.2.2019