Annika Meinander, Docent, PhD
Academy of Finland Research Fellow 1.9.2914-31.8.2019
Senior Lecturer (Akademilektor)
Fanny Sundqvist, MSc student
Sabrina Benoit, MSc student
Faculty of Science and Engineering
BioCity, 2nd floor
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.
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
The Academy of Finland
The Sigrid Jusélius Foundation
The Magnus Ehrnrooth Foundation
The Liv och Hälsa Foundation
The Doctoral Network of Molecular Biosciences (MolBio)
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.