Tuesday, June 7, 2016

Lecture 2: Nash Rochman (Sean Sun Lab)

To Grow is Not Enough

E. coli cell cycle duration distributions measured
at constant nutrient conditions. [1]
The mantra, “Survival of the Fittest,” coined by Spencer and popularized by Darwin himself, pervades every corner of biology. Fitness is usually defined to be the “birth-rate” or the rate at which new individuals are added to the population. Cooperative and multicellular systems may require a more complicated definition; but often even these phenomena are shown to derive from the maximization of total sustainable single cell number. In the case of non-cooperative, single cell species (e.g. bacteria at low cell density), fitness as birth-rate is accepted. For such a population during exponential growth, the number of cells in an ensemble can be well described as a function of time if we know the initial number N0, and the cell cycle duration τ, yielding N(t) = N0 exp(ln(2)t/τ). In this way the constant r = ln(2)/τ, often labeled the“growth-rate”, is used to measure fitness - the larger r and the faster an organism grows, the fitter it is.

Quantitative single cell measurements have shown that cell cycle duration (CCD, the time between cell divisions) for diverse cell types is a noisy variable. The underlying distribution of CCD is mean scalable with a universal shape for many cell types in a variety of environments. In their recent article, Nash Rochman and Sean Sun from Johns Hopkins mechanical engineering department have developed a phenomenological model for the regulation of cellular division time distributions determining both bulk growth rate and ensemble fluctuations. In this model, they propose a cellular ‘‘fitness’’ function which incorporates not only growth rate, which is maximized when fluctuations are minimized, but also ensemble response time to environmental stimulus which decreases for increasing fluctuations. Experimental single cell division data is collected on a population of isogenic cells subjected to varying environmental stimuli and compared to the model. The authors then have shown through both experiment and theory that increasing the amount of noise in the regulation of the cell cycle negatively impacts the growth rate, but positively correlates with improved cellular response to fluctuating environments. These results suggest that even non-cooperative cells in exponential growth phase do not optimize fitness through growth rate alone, but also optimize adaptability to changing conditions. In a manner similar to genetic evolution, increasing the noise in biochemical processes correlates with improved response of the system to environmental changes.
Nash's theory compared with eight step environmental change experiments. The experimental distributions are displayed using colors with highest probability in red and lowest probability in blue. The black lines are the model predictions for the average. [1]
Nash’s Article:
[1]: Rochman, Nash, Fangwei Si, and Sean X. Sun. "To Grow is Not Enough: Impact of Noise on Cell Environmental Response and Fitness." arXiv preprint arXiv:1603.01579 (2016).

Good reads on the subject:
P1: Hashimoto, Mikihiro, et al. "Noise-driven growth rate gain in clonal cellular populations." Proceedings of the National Academy of Sciences (2016): 201519412.
P3: Stukalin, Evgeny B., et al. "Age-dependent stochastic models for understanding population fluctuations in continuously cultured cells." Journal of The Royal Society Interface 10.85 (2013): 20130325.

Nash Rochman studied chemical physics and mathematics in college (started at Bard College at Simon’s Rock and transferred to Brown) taking a particular interest in evolutionary dynamics which brought him to the ChemBE department here at Hopkins for his PhD. With his advisor Sean Sun (MechE), he has become engaged in a variety of problems motivated by exciting analytical predictions that also provide the potential for convincing experimental verification. When not in the office/lab, he likes to play and compose music – playing mostly jazz (trumpet) and writing mostly concert music.

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