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Laboratory Profile
Principal Investigator: Daphne Atlas
1) The molecular mechanism of fast transmitter release
2) Oxidative stress related disorders: Developing potential drugs to treat
Parkinson’s, Alzheimer’s and other oxidative stress related disorders
Location: Silberman, Wing 1, 6th floor, Room 1-607
Communication:
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E-Mail: [email protected]
Phone: 6585406
Web: http://biolchem.huji.ac.il/atlash/atlas.html
Brief Description of Research:
1) The mechanism of transmitter release is not fully understood. We explore whether the voltage
gated calcium channel could serve as the molecular On/Off signaling switch, where the predominance of
a conformational change in Ca2+-bound channel provides for the fast secretory process.
We use the heterologous Xenopus oocytes expression system to study direct interactions of the
channel co-expressed in combination with the exocytotic proteins by monitoring channel kinetics. We
use bovine-chromaffin cells to study direct effects of channel and exocytotic protein mutants on secretion.
We use semliki forest viral infected cells, monitoring direct effects on secretion from as ingle cell and
single vesicles by amperometry.
2) We are developing thioredoxin mimetic peptides and test their efficacy at alleviating oxidative
stress using a large number of primary and cell cultures, as well as animal models. We test for rescue the
cells form apoptosis, looking at MAPK phosphorylation and NF-KB nuclear translocation, as well as cell
viability.
Techniques used include: molecular biology (site directed mutagenesis) preparation of RNA, cloning,
expression in oocytes; preparation of Semliki forest viruses; amperometry; electrophysiology, western
blot analysis; biochemistry,
Proposed Research Projects:
Topic 1 Demonstrating that he channel serves as the molecular On/Off signaling switch, showing
the predominance of a conformational change in Ca2+-bound channel that provides for the fast secretory
process.
Topic 2: Developing small molecular weight thioredoxin peptides and testing their efficacy at
reversing cell death and inflammation