AgreenSkills session, year: 2nd session, 2014
Receiving laboratory: PRC Reproductive and Behavioural Physiology Tours, France
Country of origin : The Netherlands
Single-chain antibody fragments targeting GPCRs to modulate social interactions
Social interaction disorders may result from early psychological trauma, exposure to noxious chemicals or neurodevelopmental abnormalities. The etiology and neurophysiological mechanisms of these disorders remain poorly understood; recent studies evidenced deficient reward processes and altered neuronal connectivity in the striatum. Oxytocin, vasopressin, kisspeptides and opioids, and their associated G protein-coupled receptors (GPCRs), are key modulators of social behaviors and widely expressed throughout striatal regions. The proposed research project aims at assessing the therapeutic potential of modulating the activity of these GPCRs using small therapeutic single-chain antibodies in vitro and in vivo, in animal models of social interaction disorders.
All along my academic cursus, my research interests focused on developing neurobiological tools to improve nervous functions. I completed my PhD studies at the Institut de Génomique Fonctionnelle (IGF, Montpellier) where I worked on a G protein coupled receptor (GPCR) of serotonin, 5HT4. I used a mutant unable to bind serotonin as a pharmacological tool to explore GPCR oligomerisation, and evidenced neuroprotective properties in vitro. I graduated in 2009 in Neurobiology.
During my first postdoctoral fellowship, at the Netherlands Institute for Neuroscience (NIC, Amsterdam), I developed in vivo strategies and innovative viral tools to relieve retinal blindness. I demonstrated visual benefits of viral vectors in a novel mouse model for CRB1 retinal dystrophies. This work led to the publication of a patent. For a couple of months, I then joined the Amsterdam Medical Centrum (AMC, Amsterdam) to establish a rodent eye clinic and explore visual function in mouse models of age-related macular disease.
Since February, I have joined the team “Deficit of Reward, GPCRs and Sociability” (DRuGS) at the Physiologie de la Reproduction et des Comportements unit (PRC, Nouzilly). I aim at developing a novel category of small therapeutic antibodies targeting GPCRs involved in social behavior. The best candidate antibodies identified through an in vitro pharmacological screening will be tested in vivo for potential improvement of behavioural deficits in mouse models of social interaction deficits. This ambitious project represents a great opportunity to acquire additional skills and to take advantage of my own expertise in GPCR pharmacology and viral vectors.
- Meirsman ACC, Le Merrer J, Pellissier LP, Diaz J, Clesse D, Kieffer BL, Becker JAJ. Mice lacking GPR88 show motor deficit, improved spatial learning and low anxiety reversed by delta opioid antagonist. Biol Psy. Under revision.
- Pellissier LP, Quinn PM, Alves CH, Vos RM, Klooster J, Flannery JG, Heimer JA, Wijnholds J. Gene Therapy into Photoreceptors and Müller Cells Restores Retinal Structure and Function in CRB1 Retinitis Pigmentosa Mouse Models. Hum Mol Genet. 2015 Jul 15;23(14):3759-71.
- Pellissier LP, Lundvig DMS, Tanimoto N, Klooster J, Vos RM, Richard F, Sothilingam V, Garcia Garrido M, Le Bivic A, Seeliger MW, Wijnholds J. CRB2 acts as a modifying factor of CRB1-related retinal dystrophies in mice. Hum Mol Genet. 2014 Jul 15;23(14):3759-71.
- Pellissier LP, Alves CH, Quinn PM, Vos RM, Tanimoto N, Lundvig DM, Dudok JJ, Hooibrink B, Richard F, Beck SC, Huber G, Sothilingam V, Garcia Garrido M, Le Bivic A, Seeliger MW, Wijnholds J. Targeted ablation of crb1 and crb2 in retinal progenitor cells mimics leber congenital amaurosis. PLoS Genet. 2013 Dec;9(12):e1003976.
– International patent PCT/NL2014/050549 (Co-inventor) entitled “Recombinant AAV-Crumbs homologue composition and methods for treating LCA-8 and progressive RP”, published 12.02.2015.
– Travel Fellowship from the French Society for Neurosciences for 6th FENS meeting in Geneva, Switzerland (2008).
– Erasmus Fellowship for a PhD traineeship in Dr Leonardo Pardo’s laboratory, Barcelona, Spain (2008).
– Grant Fellowship from the Dutch Uitzicht (blindness funds) in 2013 (2k €) and 2014 (14k €).
– Assistant Professorship from Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM) (2005-2008).
– “MNRT” PhD Fellowship from the French Ministry of Education and Research (2005-2008).