Jan Skotheim

Honors and Awards

• Postdoctoral Fellowship (F32), NIH (2006-2008)
• Career Award at the Scientific Interface, Burroughs Wellcome Fund (2008)

Professional Education

Postdoctoral Advisees

Andreas Doncic

Web Site Links

• Skotheim Lab

Research Interests

Underlying the wonderful diversity of natural forms is the ability of an organism to grow into its appropriate shape. Regulation ensures that cells grow, divide and differentiate so that the organism and its constitutive parts are properly proportioned and of suitable size. Although the size-control mechanism active in an individual cell is of fundamental importance to this process, it is difficult to isolate and study in complex multi-cellular systems and remains poorly understood. It is therefore of interest to study size control in unicellular organisms, which are governed by simpler physiology: proliferate rapidly whenever environmental conditions permit. Therefore, the laboratory studies size control in budding yeast, a genetically tractable eukaryotic organism. Previous studies of the budding yeast cell cycle, which couples growth and division, have revealed mechanisms shared by both yeasts and humans. This leads me to believe our findings will be of general interest, particularly since mammalian size control genes are frequently mutated in cancers.

In the 1970s, Lee Hartwell and colleagues attributed size control to a point between cell birth and DNA replication. Upon passage through the size-control checkpoint, budding yeast irreversibly commit to division. This checkpoint was therefore called the Start of the cell cycle. The last 30 years have seen rapid advances in our understanding of the molecular interactions in the cell cycle. Yet, in spite of all this exquisite molecular detail fundamental questions remain unanswered: What makes this transition irreversible? Where in this sequence of molecular interactions does size control occur? How does a cell compute its own size? The laboratory aims to address such systems-level questions.

A central aim of the burgeoning field of systems biology is to understand the principles governing genetic control networks. I believe finding the principles underlying genetic circuits will occur through detailed...

Publications

• Positive feedback of G1 cyclins ensures coherent cell cycle entry. Skotheim JM, Di Talia S, Siggia ED, Cross FR. Nature. 2008; 454 (7202): 291-6