How proteins are targeted to sub-cellular compartments is a question that has driven Trevor Lithgow's curiosity in science since his PhD work with Nick Hoogenraad and Peter Høj. Pursuing this question, Trevor was fortunate enough to be a postdoc with Jeff Schatz at the University of Basel's interdisciplinary Biocenter. Basel provides both a fabulous scientific environment and all the most charming things that small European cities offer. In just over two years in Jeff's lab, Trevor and his colleagues cloned the genes encoding the Tom20 and Tom22 subunits of the TOM (Translocase of the Outer Mitochondrial membrane) complex. Using a combination of biochemistry and yeast genetics, they detailed the step-by-step pathway for protein recognition and import by the TOM complex, and how this initiates protein transport into all sub-compartments of the mitochondrion.
At the University of Melbourne, two important collaborations were initiated that advanced the understanding of protein targeting in a new direction: Vladimir Likic helped Trevor use hidden Markov models, based on the sequences of each of the components for the pathway in yeast, to pose the first model for the evolution of the mitochondrial protein import pathway. In collaboration with Pavel Dolezal from Prague, Trevor's group discovered that the mitochondrial protein import pathway is also found in 'primitive' eukaryotes like Giardia – organisms that had previously been thought to be so primitive as to not have ever gained mitochondria! It is now clear that mitochondria are a defining feature of all eukaryotes, however, some organisms have mitochondria so metabolically specialised as to be hard to recognise.
Trevor's group recently discovered that mitochondrial outer membrane proteins are assembled by a machine, the SAM (for Sorting and Assembly Machinery) complex, that was derived from the bacterial protein Omp85. This has led to a new series of projects in his lab, in collaboration with colleagues at Monash University and the University of Melbourne, which apply the biochemical approaches developed in studying the mitochondrial membrane assembly to dissecting the process of bacterial outer membrane assembly. Some of the most important proteins assembled into bacterial outer membranes are the transporters that allow pathogenic bacteria to secrete 'effector' proteins, the proteins that effect changes in host cells. Trevor's fundamental work on understanding protein targeting is thus enabling a rapid in-road to studies that promise important translational outcomes.