Project Details
Projekt
Transcriptional regulation in the Drosophila circadian clock network.
Applicant
Dr. Matthias Schlichting
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2015 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 288916993
In order to predict the cyclic changes of the environment during the alternation of day and night, all so far investigated organisms have developed circadian clocks, which lead to an increase in fitness. In animals the central oscillator is located in the brain and consists of several thousand neurons in the Suprachiasmatic Nucleus (SCN) in mammals, or of up to several hundred neurons distributed in the lateral and dorsal brain in insects. One of the best investigated model organisms is Drosophila melanogaster which possesses 150 clock neurons which can be subdivided into several clusters. These neurons are strongly interconnected and form a network in which external stimuli are integrated and changes in physiology are driven. However, little is known about how the neuronal interaction affects the molecular mechanism of the circadian clock. This mechanism consists of several interlocked feedback loops in which clock proteins re-enter the nucleus and thereby inhibit their own transcription. As the majority of the clock proteins are either transcriptional activators or transcriptional repressors I want to go back on the transcriptional level and investigate, how transcription is regulated as a function of time. To do so I want to develop a live imaging assay based on the MS2 stem loop system which will allow me to follow transcription within certain clock neurons in the explanted brain. Once established this tool can be used to record transcription in real-time while manipulating single neuron clusters of the network. The results will give first mechanistic evidence of how the clock mechanism is synchronized among the neuronal network.
DFG Programme
Research Fellowships
International Connection
USA
