Receptor biology and signaling
Our research aims to increase the understanding of basic pharmacology and underlying mechanisms of signal transduction and signaling specificity mediated by the Class Frizzled (FZD) receptors.
In mammals 10 FZDs (FZD1-10) are known. The FZDs are - among other ligands - activated by 19 mammalian WNTs, a group of secreted lipoglycoproteins with an important role in embryonic development, stem cell regulation and human diseases, such as cancer. So far, it remains obscure, which WNTs activate which FZDs and how ligand binding specifies the downstream signaling events.
Our goal is to map WNT-FZD interaction profiles and to characterize basic pharmacological parameters of distinct WNT/FZD pairs. The ultimate goal, of course, is to find mechanisms that could be employed at therepeutic targets to improve current therapy in human disease as diverse as cancer, neurodegenerative diseases, bone disease, etc.
Using biochemical and anatomical as well as live-cell imaging techniques the dynamics of receptor localisation and association of intracellular signalling molecules are investigated in recombinant cell systems and glial cellular models as well as in vivo.
Javier Becerril Ortega
|PhD, postdoctoral fellow|
|Jenny Dahlström||Med kand, master's student|
|Tilman Polonio||Student from Heidelberg University/ Germany|
|Roger Helbig||Phd, postdoctoral fellow|
|Tobias Ludwig||Student from the Free University of Berlin, Germany|
Natália Assaife Lopes
|PhD student, Faculty of Medicine, University of Lisbon, Portugal|
|Master's student from the Free University of Berlin, Germany|
|Frank Brand||Master's student from the Lausitz University of Applied Sciences, Germany|
The image shows the subcellular distribution of dishevelled (DVL2-myc; red) in transiently transfected Hek293 cells. DVL2-myc is either distributed evenly throughout the cytoplasm, or aggregates in a punctate pattern of variable size (see also Bryja et al, J Cell Sci 2007).
The general aim of the project is to generate pharmacological information about the Wnt/Frizzled signaling system as well as to clarify some major questions regarding Frizzled-mediated cellular communication. Issues such as WNT-FZD interaction and selectivity, signaling trafficking, FZD coupling to the phosphoprotein Disheveled as well as heterotrimeric G proteins are the focus of our work. To investigate those questions we use protein biochemistry, determination of second messengers, Calcium imaging, confocal microscopy and live cell imaging.
Graphical abstract from Halleskog et al 2013 (Cellular Signalling)
In addition to the pharmacological assessment of FZD function, we try to understand the role of WNT/FZD signaling in the macrophages of the brain, the microglia. Our recent publication (PhD project of Carina Halleskog) shed light on the proinflammatory effects of WNTs on microglia. These cells have also provided exciting insight into the role of heterotrimeric G proteins in WNT signaling in a physiologically relevant cellular environment with natural receptor stoichiometry.
Research support - past and present
Vetenskapsrådet, Hjärnfonden, Cancerfonden, Karolinska Institutet, Knut & Alice Wallenberg Stiftelse, Signhild Engkvists Stiftelse, Tore Nilson Stiftelse, Signe & Olof Wallenius Stiftelse, Max & Edith Follins Stiftelse, Fernströms Stiftelsen, Alex & Eva Wallström Stiftelse, Jeanssons Stiftelse, Åke Wiberg Stiftelse, Åhlén Stiftelse, Socialstyrelsen, STINT, KI/NIH Joint PhD, KID
Master's and PhD projects
Please see Master's and PhD projects from the lab.
Interested applicants should contact group leader Gunnar Schulte directly with inquiries.
I would be happy to assist with applications for external support in form of postdoctoral or PhD student fellowships (see list pdf ). I strongly encourage fellows eligible for postdoctoral application to Hjärnfonden and SSMF to contact me with a letter of interest, CV and letters of recommendation.
Please see Gallery - Gunnar Schulte group