THE 2018 BECKMAN COULTER DISCOVERY SCIENCE AWARD: BOSTJAN KOBE
Institute for Molecular Bioscience
University of Queensland
I grew up in Ljubljana, the capital of Slovenia. Against the advice of my organic chemist dad, I went to study chemistry at the University of Ljubljana, and determined a small-molecule crystal structure for my diploma work. This experience led to an interest in the structures of biological macromolecules. Because there were no macromolecular crystallography labs in Slovenia at the time, I headed overseas to do a PhD at the University of Texas Southwestern Medical Center in Dallas. A lab rotation led to a PhD project with Hans Deisenhofer, who was awarded the Nobel Prize for his work on the photosynthetic reaction centre a few years earlier. After a couple of years of little success, my risky project finally led to one of the first structures of a protein made of amino-acid repeats (the leucine-rich repeat [LRR] protein ribonuclease inhibitor).
The subsequent decision to come to Australia was only partially scientific, but a postdoctoral position with Bruce Kemp at St Vincent’s Institute (SVI) turned out to be a great choice and gave me both some independence in my structural work, and exposure to world-class biochemistry in the area of protein phosphorylation. After some success with my work on protein kinases, proteins regulated by phosphorylation and intrasteric regulation, and viral fusion proteins, Bruce encouraged me to apply for a Wellcome Senior Research Fellowship, which enabled me to start an independent group at SVI.
In new projects I started in my group, I tried to combine my interests in repeat proteins and regulatory mechanisms. One protein that fit the bill was the nuclear transport factor importin-alpha, featuring armadillo repeats and autoregulation. The nuclear transport project kept us busy for many years, leading from structural biology also into the computational prediction of nuclear localisation signals. In another computational project, we developed a simple structure-based approach for the prediction of protein phosphorylation sites, Predikin, still one of the most successful tools available today.
Because of the difficulty to attract students to SVI as a new group leader, and the interest in getting involved in teaching, I applied for an Academic position at the University of Queensland (UQ). With structural genomics embraced around the world at the time, we decided with David Hume and Jenny Martin to use a focussed structural genomics approach to characterise proteins with important roles in macrophage cells. While this project never grew to large scale, it not only produced many good papers but also led to the adoption of a ‘high-throughput’ mentality in other projects in the lab. It also led to the lab focussing on infection and immunity, in particular currently on mammalian and plant innate immunity, and molecular mechanisms of virulence by pathogens. The identification of a filamentous assembly by Toll-like receptor adaptors also led us to embrace the cryo-electron microscopy technique, and UQ has been lucky to raise funds for a new state-of-the-art electron microscope coming soon.