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Title: Phenotypic variability, cell size and population fitness
Author: Crotti, Pablo
ISNI:       0000 0004 6059 1746
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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In all biological systems, phenotypes are quantitative measures of an organism's traits. To understand the relation between a genotype and phenotypes, the influence of genetic perturbations, such as gene deletions, on phenotypes is studied. Although it is common practice to look at the mean value of phenotypes to detect changes, it is less common to model such modifications by considering phenotypic variability. However, phenotypic variability could also contain important information about the phenotype-genotype map. Also, phenotypic variability is a determinant of an organism's robustness and fitness. This thesis is a collection of five studies devised to identify and analyse phenotypic variability in S. pombe, S. cerevisiae and E. coli. The first chapter determines the probabilistic nature of the dynamic transition from quiescence to proliferation in S. pombe. Based on the viability and the random nature of the quiescence of knockout genes, we demonstrate that two competing stochastic models explain the data equally well. The second and third chapters provide novel approaches to identifying mutant genes that increase/decrease phenotypic variability throughout the cell cycle of S. cerevisiae. Using machine learning algorithms, we observe that mutants divide in four categories acting positively and/or negatively on phenotypic variability. Additionally, we show that phenotypic robustness is inversely related to cell fitness. The fourth chapter builds morphological interaction networks in S. cerevisiae. By employing a Bayesian network framework, we show that cell size dictates nuclear size throughout most of the cell cycle. The fifth chapter investigates the growth rate of bacterial populations subject to fluctuations in the variance of their cell size distributions. By employing a population balance equation combined with an agent-based model, our results indicate that the cell size distribution affects the growth rate. Moreover, we show that cells possess a cell size regulator within their cycle.
Supervisor: Shahrezaei, Vahid Sponsor: Engineering and Physical Sciences Research Council ; Imperial College London
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral