Research Projects

How complex multicellular life evolves from relatively simpler unicellular organisms is a fundamental question in biology. A particularly challenging unresolved problem concerns how cell differentiation originates evolutionarily to give rise to new cell types. Specifically, although many experimental studies have revealed the nuances of how already evolved cell differentiation unfolds during the development of extant organisms, no experimental study has investigated the origin of cell differentiation in action by evolving a new cell type de novo in the laboratory. My proposal aims to resolve this fundamental knowledge gap. This gap exists primarily because most existing studies have only evolved microscopic multicellularity from unicellular ancestors, and such microscopic sizes fail to utilize environmental gradients as cues for cell differentiation. I am poised to resolve this issue because I have recently evolved obligately multicellular Escherichia coli that can grow repeatably as an elongated wormlike structure (approximately 10 cm long) along a local vertical environmental gradient, exhibiting closely packed cells at the air liquid interface (where oxygen availability is maximum) while expressing loosely packed cells in the deeper regions with lower oxygen supply. We will conduct experimental evolution with these obligately multicellular bacteria along such an oxygen gradient and select for generalist gene expression over the course of 100 days. This should lead to cells with identical genomes but different transcriptomes within the same organism. Using spatial transcriptomics, genomics, and microscopy, this first-of-its kind experiment will reveal how cell differentiation originates. As bacteria were the first organisms to evolve cell differentiation, our model system is pertinent in this context. In the next module, we will study the effects of facultative multicellularity on the interactions between coinfecting pathogens. Specifically, we will determine if environmentally induced multicellularity can facilitate the co-existence of antagonistic bacteria by segregating them spatially and reducing their interactions. To this end, we will use two opportunistic human pathogens (Pseudomonas aeruginosa and Staphylococcus aureus) that have proven to be extremely difficult to coculture in the lab, but are frequently found in coinfections. We will test if spatial segregation via multicellularity can aid in their co-existence. In the final module, we will investigate how the cell shape influences the evolution of multicellularity. This question derives from the fundamental biophysical notion that elongated cells can be packed more efficiently than spherical ones. Using E. coli cell shape mutants as ancestors, we will test if elongated cell shapes accelerate the evolution of macroscopic multicellularity. Taken together, the three proposals would address multiple fundamental unanswered questions at the interface of evolution and cell biology.