Projects

Traditionally, inhibition has been considered to be static. Our research has played a significant role in shaping this new idea that GABAergic inhibition is dynamic, allowing flexible, input-specific adaptations at excitatory connections. Hence, our research focuses on novel aspects of “versatility” within inhibitory neurotransmission. Furthermore, identification and characterization distinct inhibitory interneuron subtypes has not been sufficient to explain how the principal cells receive and interpret this information in a relevant fashion. Hence, our specific research projects address this issue by tackling specific mechanisms that allow inhibitory postsynapse to adapt dynamically to fluctuations in inputs. 

 

1.  Gephyrin post-translational modification facilitates dynamic adaptation in GABAergic neurotransmission.

A major tenet of this project is that synaptic adaptability depends on signaling cascades regulating in parallel the efficacy of glutamatergic and GABAergic transmission. We employ state of the art molecular tools to manipulate selective neuronal population in a Cre dependent manner in vivo and in collaboration with Prof. Weber (IPT, UZH) we study the functional consequences of dynamic GABAergic neurotransmission using 2-Photon Ca2+ imaging.  

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2.  Circadian fluctuations in synaptic mRNA levels mediate neurotransmission plasticity.

In collaboration with the lab of Prof. Brown (IPT, UZH) we have uncovered a novel molecular component within the neuronal clock unit consisting of DBHS proteins NONO, SFPQ, and PSPC1, whose function converge at GABAergic postsynapse. We employ next generation RNA seq, RIP seq, quantitative MS/MS analysis, biochemistry and neuro-morphology to study circadian output-dependent adaptation at inhibitory synapse.  

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3.  Extracellular matrix shapes GABAergic synapse plasticity.

Half-life of memory encoding proteins is a critical factor for any hypothesis that posits that synaptic strength is a marker for memory. The influence of extracellular matrix in mediating connectivity and facilitating signalling that encodes a previous experience remains unexplored. This project will employ in vitro primary neuron culture and in vivo conditional KO mouse model to characterize a novel extracellular matrix protein for synaptic remodeling during memory consolidation.

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4.  Novel gephyrin point-mutant mouse models to understand the GABAergic bases for neurological disorders.

Individual networks within the brain showcase different properties at different level (neurons, neuronal circuits, and systems). Hence, it is important not just to understand how the individual synapses work but also to understand how properties change at the level of neuronal circuit and system with specific alteration(s) within synapses. We employ, neuro-morphological, biochemical, behavioural, and functional analysis to characterize our CRISPR/cas9 based gephyrin knock-in mice and gephyrin conditional knock-in mice, in the context of neurological disorders.

 

 The projects and techniques within the group are diverse. Interested students can directly apply via email describing their reason to join our research team. A strong scientific curiosity is a necessity to fit into our Internationally diverse and dynamic work environment.

 

Techniques

Basic molecular biology, protein biochemistry, immunostaining, dynamic live imaging, confocal imaging, cell biology (sub cellular fractionations, targeting, trafficking), functional genomics (RNA seq, RIP seq, MS/MS analysis), primary neuron culture, in vivo Ca2+ imaging and electrophysiology.

We collaborate with both local and international groups to complement our skills and knowledge.