Shedding light on circadian rhythms in drosophila : examining the mechanisms of timeless Rna cycling and the role of a Pas domain-containing kinase / Garrick Wang.

Format:

• Book
• Manuscript
• Microformat
• Thesis/Dissertation

Author/Creator:

• Wang, Garrick.

Contributor:

• Sehgal, Amita, advisor.
• University of Pennsylvania.

Language:

English

Subjects (All):

• Penn dissertations--Cell and molecular biology.
• Cell and molecular biology--Penn dissertations.
• Cell and Molecular Biology.
• Academic Dissertations as Topic.

Medical Subjects:

• Cell and Molecular Biology.
• Academic Dissertations as Topic.

Local Subjects:

• Penn dissertations--Cell and molecular biology.
• Cell and molecular biology--Penn dissertations.

Physical Description:

ix, 142 pages : illustrations ; 29 cm

Production:

2002.

Summary:

Like most other organisms, Drosophila display a daily or circadian pattern of physiological outputs that is regulated by an endogenous clock. This clock is dependent on the rhythmic expression of the proteins PERIOD and TIMELESS. Both proteins negatively regulate their own transcription through an interaction with their transcriptional activators, CYCLE and CLOCK. CYCLE and CLOCK activate transcription by recognizing a DNA sequence in the promoter of target genes known as an E-box. PERIOD, CYCLE, and CLOCK contain a PAS domain, which is a protein-protein interaction domain seen in a number of proteins involved in circadian rhythms and light sensitivity. This work addresses the mechanisms involved in the cycling of timeless RNA and behavioral rhythmicity, and examines how a newly discovered kinase with a PAS domain contributes to circadian rhythms and light sensitivity. In the first half of this work, we show that the upstream E-box in the timeless gene is required for behavioral rhythmicity but is insufficient to drive high-amplitude RNA cycling. High amplitude timeless RNA cycling requires genomic sequences, implying a role for intronic sequences in maintaining wild-type RNA expression. In addition, we demonstrate that an in vivo complex containing CYCLE and CLOCK binds the E box-containing timeless promoter sequence and can be detected at all times of day. Thus, we demonstrate that rhythmic timeless expression involves a number of cis- and trans-acting factors, but this RNA cycling is not required for behavioral rhythmicity. In the second half of this work, we examine the role in circadian rhythms of a kinase that contains a PAS domain. This PAS Kinase interacts with the Drosophila circadian photoreceptor CRYPTOCHROME. RNA expression of the PAS kinase is not under circadian control and is not affected in clock mutants. Protein expression in the head is strongest in the photoreceptor cells. Overexpression of the PAS kinase leads to an increased sensitivity to light in transgenic flies. Hence, this PAS kinase does not seem to affect the central clock of Drosophila, but may modulate sensitivity of the clock to light. This work sheds light on the mechanisms involved with maintaining circadian function in Drosophila.

Notes:

• Supervisor: Amita Sehgal.
• Thesis (Ph.D. in Cell and Molecular Biology) -- University of Pennsylvania, 2002.
• Includes bibliographical references.

Local Notes:

University Microfilms order no.: 3043973.

OCLC:

244972728