The minimal requirements for a living system are often listed as follows: i) a living system must have a specific identity and be able to preserve it (compartmentalization) ; ii) it must sustain itself by using energy from its environment to manufacture at least some of its components from resources in the environment (metabolism) ; iii) the system must be capable of growth and self-replication (a prerequisite here being a genetic building plan); finally iv) it must be capable of adaptation (open-ended evolvability). The design of artificial chemical systems or protocells from the bottom up (Szostak, 2001), fulfilling these requirements has been the subject of numerous studies. Usually such chemical systems are conceived around the encapsulation of a set of genes along with the transcription-translation machinery within liposomes/vesicles (Yutetsu, 2009). The generated artificial systems have many of the basic characteristics of a living system, but usually lack the gene mediated regulation functions that natural cells possess. To address this issue, we are attempting a systemic approach (Rasmussen, 2004) in implementing a simple, chemical system that contains three major types of molecules (information-bearing, metabolic and amphiphile molecules). These molecules through self-assembly processes will aggregate to form a complete protocell with its own information, metabolism and container components. This system should be capable of performing independently all the necessary metabolic steps, e.g., amphiphile production and non-enzymatic polymerization of the information building blocks, which will lead to its replication. Our proposed system is composed of a chemical mixture of fatty acids that form bilayers (compartments), nucleic acids (NAs) with a hydrophobic moiety, and metabolic complexes or photosensitizers which can harvest energy. To truly simplify our design while fulfilling the design requirements, the regulation of the metabolism is mediated by information molecules. That is, the NAs acts as a sequence-specific, metabolic mediator by serving as electron relay to a ruthenium complex, the photosensitizer/catalyst. The metabolic catalytic unit converts the hydrophobic container precursor molecules into amphiphiles or into nucleic acid oligomers that can be non-enzymatically ligated, thus directly linking the metabolism with information. We will report on the major steps towards the realization of the design and the already demonstrated advantages of the systemic approach in unravelling interactions (Declue, 2009; Maurer, 2011) between the components and their significances for the self-maintenance and self-replication of a protocell. References DeClue, MS, Monnard, P-A, Bailey, JA, Maurer, SE, Collis, GE, Ziock, H-J, Rasmussen, S, and Boncella, JM (2009) J. Am. Chem. Soc., 131, 931-933. Maurer, SE, Declue, MS, Albertsen, AN, Dörr, M, Kuiper, DS, Ziock, H, Rasmussen, S, Boncella, JM, and Monnard, P-A (2011) ChemPhysChem, in press. Yutetsu, K, Pasquale, S, Ueda, T, and Luisi, PL, (2009) Biochim. Biophys. Acta, 1788, 567- 574. Rasmussen S, Chen L, Deamer D, Krakauer, DC, Packard, NH, Stadler, PF and Bedau, MA (2004) Science, 303, 963-965. Szostak, JW, Bartel, DP and Luisi, PL (2001) Nature, 409, 387-390.