Quantitative Biosciences Thesis Proposal
School of Biological Sciences
Advisor: Dr. William Ratcliff, School of Biological Sciences
Open to the Community
Title: Co-opting cellular heterogeneity in unicellular organisms for spatial cell differentiation
Monday, September 30th, 2019, 2:00 p.m.
Cherry Emerson, Room #204
Dr. Annalise Paaby; School of Biological Sciences, Georgia Tech
Dr. Alberto Stolfi; School of Biological Sciences, Georgia Tech
Dr. Peter Yunker; School of Physics, Georgia Tech
The origin of multicellular organisms with cell differentiation was a key step in the evolution of complex life. Despite its importance, little is known how cell differentiation arises in simple clusters of cells. One hypothesis is that pre-existing cellular heterogeneity in unicellular organisms (resulting from asymmetric cell division, phenotypic plasticity, etc.) can be co-opted for spatial cell differentiation in nascent multicellularity. However, direct experimental evidence for this hypothesis remains scarce, mainly because these transitions are ancient and their earliest steps are obscured by extinction. In my thesis research, I will circumvent these limitations and directly test this hypothesis by evolving multicellularity de novo in the lab using two unicellular organisms, the budding yeast Saccharomyces cerevisiae and the choanoflagellate Salpingoeca rosetta, which have different ways of generating cellular heterogeneity and potentially co-opting it for spatial cell differentiation.
S. cerevisiae exhibits asymmetric cell division (manifested as replicative aging) and phenotypic plasticity, which could be co-opted for age- and microenvironment-related cellular differentiation. Our lab has evolved yeast under selection for larger size, resulting in multicellular ‘snowflake’ yeast clusters. Over two years of evolution, we have indeed observed signs of evolved adaptive cellular heterogeneity that may be attributed to modulation of replicative aging. I will examine the evolution of cellular heterogeneity in snowflake yeast and disentangle its contributing factors (cell age and microenvironment) by quantitative single-cell profiling based on imaging and single-cell RNA-seq, as well as test its effect on multicellular fitness by modeling and competition assays.
The choanoflagellate S. rosetta is one of the closest living unicellular relatives of animals, and a model organism for studying animal origins. It has the remarkable ability to alternate between multiple temporal cell types (including facultative ‘rosette’ colonies) in response to environmental variations, offering a unique opportunity for studying the transition from temporal to spatial cell differentiation using experimental evolution. I will subject rosette colonies of S. rosetta to selection for larger size and for multicellular adhesion to a substrate. While it is impossible to know how they will respond to this selection, the spatial integration of pre-existing temporally regulated cell types would provide a clear advantage in these environments.