Tel Aviv University, Department for Neurobiology, Life Sciences Faculty
"The Molecular Mechanisms of Synaptic Function Under Normal and Pathological Conditions"
The human brain is composed of more than a trillion (1012) nerve cells whose signal-carrying protrusions are interconnected at special points of contact called synapses. Neurotransmitter release at the synapse is a multi-step process that is coordinated by a large number of synaptic proteins and depends on proper protein-protein interactions. Modulation of these processes is believed to underlie the processes of learning and memory. Our main interest is to study the molecular mechanisms of these processes under normal conditions and during neurodegenerative diseases such as Huntington and Alzheimer diseases. In the last years we have been investigating the function of key synaptic proteins in this process using molecular biology, electrophysiology, biochemistry, imaging and computer simulation techniques. To that aim we took advantage of a unique experimental approach that allows efficient manipulations of the level and composition of specific proteins in define neurons, using transgenic mice model and overexpression systems. The approach allows studying structure-function relationships of synaptic proteins and their role in normal and pathological conditions. We perform detail electrophysiological and fluorescent measurements from specific neurons from specific area of the mouse brain and compare the phenotype to neurons expressing the different mutated proteins. Currently, we investigate the function of Munc13, Munc18, tomosyn, PLD and DOC2 in exocytosis.
In addition we have developed a novel simulation program that describes the process of exocytosis as dynamic interactions between synaptic proteins. This study provides an excellent platform to predict and quantify the effects of protein manipulations on exocytosis. We have started to expend this approach and our long-term goal is to develop a general methodology that will allow modeling the dynamics of complex interactions of hundreds of proteins in processes like signal transduction or neuronal communication. This will provide researchers from the biomedical field with a tool to understand how large sets of proteins assemble together to execute cellular processes. These models once available, can be used to test possible strategies for altering or bypassing specific steps in these processes during pathological conditions, thus allowing efficient curing and recovery of diseases.
Updated Details January 2011 :
Prof. Uri Ashery, Ph.D.
Chair, Department of Neurobiology.
Head, Interdisciplinary Doctoral Program for Neuroscience (IDPN)
Dept. of Neurobiology
Sherman building room 719
The George S. Wise Faculty of Life Sciences
Tel-Aviv University, Ramat Aviv
Tel Aviv 69978
PhD Program: http://neuroscience.tau.ac.il/IDPN/