POSTERS - BLAST X - University of Utah

BLAST X Thurs. Evening Session
A SYSTEMS BIOLOGY APPROACH TO UNDERSTANDING HOW BACILLUS MAKES UP ITS
MIND
Arnaud Chastanet 1 , Guocheng Yuan 2 , Thomas M. Norman 1 , Jun Liu 3 and Richard Losick 1
1 Molecular and Cellular Biology Department, Harvard University,
2 Department of Biostatistics and Computational Biology, Harvard School of Public Health,
3 Department of Statistics, Harvard University.
Understanding how cells make decisions and differentiate are key biological questions.
Mechanisms underlying such behaviors integrate multiple environmental signals in intricate
networks in order to appropriately respond to the situations. The sporulation process that takes
place in Bacillus subtilis under adverse conditions perfectly exemplifies this kind of question. For
this, numerous signals and control systems are integrated at the level of a ”decider” protein
called Spo0A, a transcriptional regulator belonging to the two-component systems family. The
decision to sporulate is taken during the first two hours after optimal sporulation conditions have
been reached. During this time, Spo0A accumulates slowly reaching a high level at hour two. It
has been previously shown that while some of its targets are activated at low concentration,
thus early on, others are switched on later, when the maximal quantity of the regulator has been
achieved. Interestingly, even in optimal conditions, only a fraction of the population will finally
decide to sporulate, a phenomenon described as bistability.
We are attempting to understand how this two-stage activation of Spo0A is achieved
through an interdisciplinary approach combining the methods of genetics and mathematics. The
time resolved picture of the regulatory process we have obtained has revealed a multiple step
process involving successive switches. First, Spo0A activity is rising during log phase, activating
some switches. Then under conditions of nutrient limitation, Spo0A is further activated to a mid
and variable extent throughout the population. During this period, “low-threshold” genes are
turned ON. In an ultimate step, a bistable switch allows Spo0A to be activated to a high level but
only in a portion of the population. These cells express high threshold genes and proceed to
sporulate.
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