The overarching goal for the Molecular Neuromodulation team is to bring together frontline gene-based technologies with in vivo gene transfer, behavioral and cognitive assessments in disease models of Parkinson’s disease and related disorders for the development of clinical therapies for tomorrow.
Towards this ultimate goal, the team works along three major areas of research, briefly outlined below:
In vivo therapeutic target identification and validation
In vivo neuronal modulation using an AAV toolbox
The emergence of gene based in vivo neuronal modulation in the form of optogenetics has brought about a number of promising technologies for selective, modulatable control of nerve cell function is the adult brain.
With this research we aim to deploy and develop novel adeno-associated viral (AAV) vector based technologies enabling “pharmacogenetic” control of selected neuronal pathways in the parkinsonian brain. The combination of transgenesis and AAV vectors will allow for temporal elucidation of mechanisms such as the induction of involuntary movements (dyskinesias) in Parkinson’s disease as well as cognitive impairments in related disorders.
In vivo gene expression studies
Building on the data generated in the above-mentioned research line, this line of projects aims to dissect cellular signaling pathways and degenerative mechanisms that are at the core of neurodegenerative disorders.
Through the utilization of transgenic reporter strains AAV vectors and next-generation molecular probes, this project aims to allow for direct FACS aided sorting of distinct, distributed neuronal populations for deep sequencing and RNAseq.
In vivo massively parallel functional genetic screening
Advancements in viral vector technology, molecular biology tools and massively-parallel sequencing strategy has opened up for an entirely new view on in vivo studies of gene function and molecular mechanisms. In this project we aim to develop a novel toolset where a priory hypothesis based, iterative dissection of function in vitro and in vivo is replaced by an unbiased massively-parallel in vivo screening approach.
Translational gene-based medicine
The Molecular Neuromodulation team works closely together with internationally leading AAV experts and clinicians to bring AAV based therapies for Parkinson’s disease to the clinic. The long-term goal of this project is to build a foundation of non-clinical and clinical experience to allow for rapid development of advanced, gene-based therapies in the future.