The encoded, heritable information that plays a large role in determining an organism’s traits is known as the organism’s genotype. In natural organisms, genotypes are specified by an organism’s DNA. By contrast, an organism’s observable traits (its phenotype) are determined by proteins produced from the information encoded in DNA. All known forms of life use this dual-molecule structure: distinct molecules for genotype vs. phenotype. Separating the molecular basis of genotype and phenotype, however, is thought to be a highly evolved approach to leveraging and expressing information, and it’s conjectured that the earliest forms of life employed a simpler system whereby one type of molecule specified both the organism’s genotype and phenotype. This grant supports work led by Job Boekhoven, a Professor of Supramolecular Chemistry at the Technical University of Munich, to construct a purely synthetic cellular system (one composed of non-biological molecules) that is at once both self-replicating and capable of evolution, yet uses a single molecule for both genotype and phenotype. Boekhoven and his team aim to develop a chemical system of self-replicating molecules that encodes heritable information (i.e. develop a genotype) and then incorporate these ‘genes’ into artificial vesicles that can divide.Some of these self-replicating molecules will be engineered to have measurable effects on the larger vesicle, affecting characteristics of the vesicle membrane and cytoplasm, thus coupling the cell’s genotype with its phenotype. This would pave the way for further experimentation, not funded by this grant, that would demonstrate that these phenotypic expressions could be adaptive or maladaptive in various environments, and thus form the basis for evolutionary selection.