Prof. Steven A. Brown

 

Main Goals, Keywords

Our group is interested in the ways in which genetic differences among individuals can provoke cellular changes that are reflected in behavior. The principal model system is the human and mouse circadian clock, studied at a molecular level.

Keywords: Circadian clock, chronotype, molecular genetics, human behavior, transcription

Group Members

1 professor, 2 postdoctoral fellows, 1 technician, 4 PhD students, 1 Master student

Previous and Current Research

Human behavior is influenced by many genetic and environmental factors; it is therefore often difficult to study by reductionist approaches.  However, it can sometimes be linked directly to biological processes that can be understood at the cellular level.  The circadian clock is one such instance:  physiologically, it affects diverse processes such as sleep-wake time, cardiac and respiratory rate, renal flow, and digestion.  Molecularly, it is present in most cells of the body and modulates the transcription of about ten percent of our genes. 

My laboratory takes two approaches to the study of the circadian clock.  Genetically, using biopsies taken from human subjects we attempt to unravel the cellular changes that give human different patterns of daily behavior. Biochemically, we purify complexes of proteins from these cells that are important to the circadian clock, and attempt to understand their function through mouse models.

Future Projects

We hope to use the real-time reporter assays that we have developed for circadian and noncircadian signaling pathways as quantitative traits in linkage and association studies based upon human primary cells.  Meanwhile, we continue to unravel the functions of the NOPS family of RNA-binding transcription factors that we have shown to be important to the circadian clock.

Techniques and Equipment

Real-time reporter luminometry, immunohistochemistry, quantitative trait analysis, primary cell culture, transgenic mouse construction and analysis

Selected Publications

• Kowalska E, Ripperger JA, Hoegger DC, Bruegger P, Buch T, Birchler T, Mueller A, Albrecht U, Contaldo C, Brown SA. NONO couples the circadian clock to the cell cycle. Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1592-9. doi: 10.1073/pnas.1213317110. Epub 2012 Dec 24.
• Kowalska E, Ripperger JA, Muheim C, Maier B, Kurihara Y, Fox AH, Kramer A, Brown SA. Distinct roles of DBHS family members in the circadian transcriptional feedback loop. Mol Cell Biol. 2012 Nov;32(22):4585-94. doi: 10.1128/MCB.00334-12. Epub 2012 Sep 10.
• Dallmann R., Viola AU., Tarokh L., Cajochen C., Brown SA. The human circadian metabolome. Proc. Natl Acad Sci USA, 109(7):2625-9. (2012)
• Brown SA. Circadian rhythms. A new histone code for clocks? Science. 2011 Sep 30;333(6051):1833-4.

Funding

Swiss National Science Foundation, Fyodor Lynen Foundation, 6th EU Framework Project EUClock

URL

http://www.pharma.uzh.ch/research/chronobiology/areas/chronobiology.html