Determinants of Expression, Assembly and Function of the Noradrenaline Transporter. The noradrenaline transporter protein that is the focus of this project is important for mental health because it belongs to the family of proteins where psychostimulants, such as cocaine, and drugs used in the treatment of depression act. The project will lead to exciting advances in our understanding of how the structure of this protein controls its functions, and potentially to the design of better antidepress ....Determinants of Expression, Assembly and Function of the Noradrenaline Transporter. The noradrenaline transporter protein that is the focus of this project is important for mental health because it belongs to the family of proteins where psychostimulants, such as cocaine, and drugs used in the treatment of depression act. The project will lead to exciting advances in our understanding of how the structure of this protein controls its functions, and potentially to the design of better antidepressant drugs and to the design of drugs to prevent the effects of cocaine.Read moreRead less
Glycerotoxin, a unique tool to investigate the dynamic interactions between N-type Ca2+ channels and the exo-endocytic machinery. Communication between neurons relies on exocytosis, a process in which synaptic vesicles containing a neurotransmitter release their content in the extracellular synaptic cleft. We have recently discovered a unique neurotoxin called glycerotoxin (GLTx), which selectively activates Ca2+ channels (Cav2.2), linked with the exocytic machinery in the Central Nervous System ....Glycerotoxin, a unique tool to investigate the dynamic interactions between N-type Ca2+ channels and the exo-endocytic machinery. Communication between neurons relies on exocytosis, a process in which synaptic vesicles containing a neurotransmitter release their content in the extracellular synaptic cleft. We have recently discovered a unique neurotoxin called glycerotoxin (GLTx), which selectively activates Ca2+ channels (Cav2.2), linked with the exocytic machinery in the Central Nervous System. GLTx provide a new tool to further dissect the role of Cav2.2 in controlling neurotransmitter release. GLTx also greatly facilitates synaptic vesicle recycling, suggesting an unexpected link between Cav2.2 activation and the compensatory endocytic machinery. Our goal is to investigate functional coupling between Cav2.2 and the exo- and endocytic machineries using GLTx.Read moreRead less
The role of zinc in synaptic transmission in the central nervous system. By regulating the strength of synaptic transmission between neurons, zinc exerts dynamic control over many physiological processes including memory formation, fear conditioning and movement control. Zinc also controls neuronal cell death pathways. There is currently much controversy about the concentration that zinc reaches in the synaptic cleft and the length of time it remains elevated. By defining these parameters, this ....The role of zinc in synaptic transmission in the central nervous system. By regulating the strength of synaptic transmission between neurons, zinc exerts dynamic control over many physiological processes including memory formation, fear conditioning and movement control. Zinc also controls neuronal cell death pathways. There is currently much controversy about the concentration that zinc reaches in the synaptic cleft and the length of time it remains elevated. By defining these parameters, this project aims to understand which proteins zinc acts upon and the molecular mechanisms by which it exerts its synapse-modulating effects. The outcomes of this project could lead to better understanding of zinc dynamics that could underpin future research into many physiological processes.Read moreRead less
The molecular basis of ionic selectivity in nicotinic-type ion channel receptors. The ability of cell membranes to transport sodium, potassium and chloride selectively is important for many physiological processes. By elucidating the mechanisms by which membrane ion channels flux chloride ions, selectively this project will have wide-ranging ramifications from understanding physiological processes to nanofluidic device design.