CXiao-02
Structural studies of mammalian circadian clock proteins
Health, human disease & diagnostics
Preferred major field of study or minimum required skills
- Major in biology, biochemistry, or chemistry will be preferred.
- Previous lab experience is highly favorable.
- Good working ethics, team work spirit and good English communication skill are required.
Scholarly significance/intellectual merit
Circadian rhythm is an intrinsic and roughly-24-hour biological clock embedded within most living organisms. The discovery of molecular mechanisms controlling the circadian rhythm won 2017 Nobel Prize in Physiology or Medicine. In mammals, circadian rhythm coordinates sleep-wake cycles,blood pressure,body temperature and liver metabolism in a daily cycle. Disruption of the clock will lead to sleep loss and many other health problems. In the past two decades,many intrinsic clock related genes have been identified. Some of these genes encode for proteins,which form complexes that bind DNA and control the biological clock at the transcriptional level. However,science lacks the structural information needed to understand the detailed mechanisms that can explain how these clock proteins establish cellular cycles or oscillation rhythms in order to anticipate change in their environment. Dr. Xiao's research group combines the use of X-ray crystallography and cryo-electron microscopy to study the structures of the mammalian clock proteins and their complexes. This structural information will deepen our understanding of circadian rhythm and will help develop new therapeutic strategies for certain diseases.
Research question(s)
Structural studies in Dr. Xiao’s research will address the following questions:
- What are the atomic structures of core circadian proteins?
- How do core circadian proteins interact each other?
- What is the mechanism of the transcriptional control of circadian rhythm?
Methods/techniques/instruments to be learned/utilized
The student will engage in hands-on activities to over-express circadian proteins for structural studies. The student will learn molecular biological skills such as DNA/protein electrophoresis, PCR, DNA ligation, protein expression, and protein chromatography. The student will obtain knowledge about start-of-the-art technology such as X-ray crystallography and cryo-electron microscopy (Cryo-EM, 2017 Nobel Prize in Chemistry).