Differently from the “traditional” MMPs whose activation occurs in the extracellular space, the most recently identified family of MMPs, the ADAM-TS family are activated intracellularly. However, not much is known about the mechanism of ADAM-TSs intracellular regulation, trafficking and interactors. The working hypothesis is that the regulation of adult plasticity is due to local release of ADAM-TSs. Therefore, understanding the intracellular pathways leading to ADAM-TSs activation and secretion will allow to modulate their release and to test this hypothesis studying the effects on synaptic plasticity.
The student will conduct imaging studies on neuronal cell lines first and primary cells afterwards, by overexpressing fluorescent-tagged ADAM-TSs or by silencing using RNA interference to dissect their intracellular pathways and understand how the activity and the secretion of the ADAM-TS are regulated at cellular level.
Our research groups are part of the NorMIc Imaging Platform (http://www.mn.uio.no/ibv/english/research/about/infrastructure/imaging/) and CINPLA (www.cinpla.org). The findings will be used in computational models in collaboration with researchers at CINPLA and after having identified the molecular mechanisms regulating MMPs activation and secretion, the results can be used to modulate ADAM-TS activity in in vivo models for testing the effect on brain plasticity.