Mathiasen group – Adhesion GPCR signalling function
We focus on investigating the signaling properties and unexplored biology of Adhesion G protein-coupled receptor (GPCRs) and the implications of this receptor family in human health and disease.
Adhesion GPCRs are crucial regulators of diverse functions in the nervous, musculoskeletal, cardiac and immune systems, and their dysregulation has been linked to a variety of diseases and cancers. In the Mathiasen lab we have a special focus on the adhesion GPCR ADGRL3 (historically latrophilin 3 or LPHN3).
ADGRL3 compose a giant protein structure that combines several functions. On the one hand, it can bridge between neurons to stabilize the synapse by binding extracellular transsynaptic protein ligands, and on the other hand, it can control intracellular signaling cascades through its transmembrane GPCR domain.
In the lab we are interested in mapping ADGRL3's basic biological functions such as how the receptor is activated, what downstream signaling cascades are turned on as a consequence of activation as well as what cellular response ADGRL3 activation leads to. To do so we combine a suite of molecular biology techniques and advanced GPCR signaling assays with the development of novel single molecule microscopy approaches.
ADGRL3 has been associated with increased risk of ADHD, and knockdown in multiple animal species leads to dopamine dysfunction, thus ADGRL3 is a potential new target for treatment of neuropsychiatric disorders that involve dopamine dysfunction such as e.g., schizophrenia. Understanding the basic signaling functions of ADGRL3 is a first step towards exploring this receptor as a target in mental health.
- Live cell GPCR signalling assays: Bioluminescence resonance energy transfer (BRET) based assays, Bioluminescence complementary assays, Förster Resonance Energy Transfer (FRET) based assays
- Microscopy techniques: Confocal microscopy, Optical tweezers, single molecule total internal reflection fluorescence microscopy
- General molecular biology techniques and mammalian cell culture.