Abstract: Circadian clocks regulate molecular oscillations that manifest into physiological and behavioral rhythms in all kingdoms of life. A long-term goal of my laboratory is to dissect the molecular network and cellular mechanisms that control the circadian oscillator in animals, and investigate how this molecular oscillator interacts with the environment and cellular metabolism to drive rhythms of physiology and behavior.

Given the similarities in design principle of circadian oscillators across kingdoms, the knowledge gained from studies using Drosophila melanogaster as a model will lead to a better universal understanding of circadian oscillator function and properties. In this presentation, I will discuss the contribution of protein posttranslational modifications (PTMs) in regulating circadian rhythm by focusing on analyzing PTMs of key transcription factors such as PERIOD (PER), a key biochemical timer of clockwork.

My laboratory has recently optimized the PTM profiling of circadian proteins in vivo using affinity purification and mass spectrometry. This breakthrough allows us to follow the temporal multi-site PTM program of PER and other clock proteins in vivo at physiological conditions throughout the circadian day in a high throughput and quantitative manner, and sets the stage for understanding how the PTM programs of clock proteins, and hence clock function, are modulated by genetic, nutrition, and environmental factors.

Suggested Reading:

  1. The Catalytic and Non catalytic Functions of the Brahma Chromatin Remodeling Protein
  2. NEMO:NLK Phosphorylates PERIOD to Initiate a Time-Delay Phosphorylation Circuit that Sets Circadian Clock Speed