@article {1741,
	title = {Metabolic constraints drive self-organization of specialized cell groups.},
	journal = {Elife},
	volume = {8},
	year = {2019},
	month = {2019 Jun 26},
	abstract = {<p>How phenotypically distinct states in isogenic cell populations appear and stably co-exist remains unresolved. We find that within a mature, clonal yeast colony developing in low glucose, cells arrange into metabolically disparate cell groups. Using this system, we model and experimentally identify metabolic constraints sufficient to drive such self-assembly. Beginning in a uniformly gluconeogenic state, cells exhibiting a contrary, high pentose phosphate pathway activity state, spontaneously appear and proliferate, in a spatially constrained manner. Gluconeogenic cells in the colony produce and provide a resource, which we identify as trehalose. Above threshold concentrations of external trehalose, cells switch to the new metabolic state and proliferate. A self-organized system establishes, where cells in this new state are sustained by trehalose consumption, which thereby restrains other cells in the trehalose producing, gluconeogenic state. Our work suggests simple physico-chemical principles that determine how isogenic cells spontaneously self-organize into structured assemblies in complimentary, specialized states.</p>
},
	issn = {2050-084X},
	doi = {10.7554/eLife.46735},
	author = {Varahan, Sriram and Walvekar, Adhish and Sinha, Vaibhhav and Krishna, Sandeep and Laxman, Sunil}
}
@article {1593,
	title = {A minimal "push-pull" bistability model explains oscillations between quiescent and proliferative cell states.},
	journal = {Mol Biol Cell},
	volume = {29},
	year = {2018},
	month = {2018 Sep 15},
	pages = {2243-2258},
	abstract = {<p>A minimal model for oscillating between quiescent and growth/proliferation states, dependent on the availability of a central metabolic resource, is presented. From the yeast metabolic cycles, metabolic oscillations in oxygen consumption are represented as transitions between quiescent and growth states. We consider metabolic resource availability, growth rates, and switching rates (between states) to model a relaxation oscillator explaining transitions between these states. This frustrated bistability model reveals a required communication between the metabolic resource that determines oscillations and the quiescent and growth state cells. Cells in each state reflect memory, or hysteresis of their current state, and "push-pull" cells from the other state. Finally, a parsimonious argument is made for a specific central metabolite as the controller of switching between quiescence and growth states. We discuss how an oscillator built around the availability of such a metabolic resource is sufficient to generally regulate oscillations between growth and quiescence through committed transitions.</p>
},
	issn = {1939-4586},
	doi = {10.1091/mbc.E18-01-0017},
	author = {Krishna, Sandeep and Laxman, Sunil}
}
