Martin Spiess investigates topogenesis and the intracellular transport of membrane proteins in eukaryotic cells. He studies the mechanism of translocon function and how proteins are sorted in the cell and transported to their designated organelles. Spiess discovered that the translocon, in particular the asymmetric polarity along the pore, determines the thermodynamic equilibrium between integration of individual proteins segments into the cell membrane and their further transport. Further studies demonstrated that the orientation of transmembrane segments are defined through the flanking charges, the folding of neighboring segments as well as the hydrophobic properties of the sequences themselves.