Bottom-up synthetic biology traditionally focuses on constructing artificial compartmentalized systems that emulate living cell functions in terms of mechanics, morphology, or metabolism. Yet, this approach also holds immense promise for studying and augmenting subcellular structures like organelles, whose intricate nature in eukaryotic life forms remains enigmatic. I will present how we harnessed droplet-based microfluidics to control the assembly of lipid-enclosed, organelle-like architectures. I present how giant unilamellar vesicles (GUVs)-based synthetic organelles (SOs) can be designed to function within natural living cells, showcasing three examples: synthetic peroxisomes that bolster cellular stress-management, synthetic endoplasmic reticulum acting as intracellular calcium stores for intercellular calcium signalling, and synthetic magnetosomes granting eukaryotic cells a magnetotactic sense. The functional integration of such synthetic organelles heralds a new era for high-throughput creation of diverse intracellular structures that can be integrated into living cells. Beyond their potential in translational nanomedicine, these in-droplet SO designs could be pivotal in astrobiology. They offer avenues for adapting terrestrial life to extraterrestrial conditions, creating biosensors for space exploration, enhancing photosynthesis for space colonization, and even safeguarding against potential new pathogens. As humanity ventures deeper into the cosmos, such synthetic organelle systems may play a central role in facilitating and safeguarding life beyond our home planet.
