Nenad Ban: “…it is a privilege to be surrounded by brilliant young co-workers and to learn from them…”
FEBS 2020 plenary lecturer Nenad Ban shares his fascination with structural biology and perspectives on life as a senior researcher
What drew you to your research field?
Ever since I remember, I was fascinated with biology. Perhaps this is because in Croatia, where I grew up, we had fairly long summer school holidays and I ended up spending several months at the Adriatic seacoast where I developed curiosity to investigate creatures of the sea. By the time I graduated from high school my focus had shifted towards biochemistry and molecular biology.
Since I am a very visual person I can best understand how things work when I see what they look like. Because of this reason I have devoted my career to studying molecular function using methods in biochemistry and structural molecular biology from crystallography to electron microscopy.
What do you see as the most important developments in your field in recent years?
Our ability to study structure and function of biological molecules has advanced dramatically over the years. Currently, the most powerful method to study large cellular assemblies in their cellular environment and in isolation is electron microscopy. This method allows us to determine structures of biological molecules at resolutions that permit complete molecular interpretations, which is a requirement to explain the chemical basis of biological processes.
Tell us about one of your favourite published papers from your lab
In my view the most stimulating research is always the research that is still in progress. Consequently, most recent results are always particularly exciting to me. Our latest discoveries revealed that mitochondrial ribosomes in trypanosomes are assembled using an elaborate assembly machinery consisting of a very large number of assembly factors. This process involves interesting molecular conformational changes and a large number of steps (Saurer, M. et al. Science 2019 – referenced in full below). It is really fascinating that in this research we were able to use electron microscopy as an analytical discovery tool to identify new cellular complexes and proteins and to learn about their cellular functions. In a way these experiments reminded me of a well-known experiment performed on a Hubble telescope when astronomer Bob Williams decided to point the telescope for 100 hours and investigate a region of the night sky that was dark with no known stars or objects present. Everybody thought it was a bad idea and a waste of telescope time. However, when the image was processed it turned out that it was not “nothing” but rather a field filled with more than 3000 galaxies; this was remarkable and changed the way people think about the universe. To detect and describe the assembly intermediates of mitochondrial ribosomes we also had to collect a large dataset using precious microscope time, without knowing what to expect, but in the end the results exceeded all our expectations and revealed a previously uncharacterized cellular process.
What’s exciting in your research area right now?
Although the role of ribosomes in protein synthesis has been known for many years, it is really exciting to see how protein synthesis is controlled in cells during development and growth, or how viruses take over the cellular protein synthesis machinery. One of the key methods that has transformed our ability to investigate the mechanisms of translation is ribosome profiling, a method that combines ribosome footprinting with next-generation RNA sequencing, allowing us to pin down the locations of ribosomes on different cellular mRNAs depending on different conditions. Combining insights based on ribosome profiling with the new methods in structural biology is an extremely powerful way to answer the questions that we are interested in.
What aspects of your life as a researcher do you most enjoy?
I see working as a lab head in academia as a unique type of profession. First, it is a privilege to be surrounded by brilliant young co-workers and to learn from them, and to work in a field where so many inspiring scientists from different backgrounds contribute to its progress. Academic work also provides quite a bit of freedom for creativity and self-management of time. However, the expectations of the scientific community and the rate of discovery is constantly increasing. Consequently, to be able to run a successful laboratory, one has to always keep up to date on recent results in the field and on recent technological developments. Although this means that one can never really feel to have “finished” the project, as every result opens new questions, I really enjoy the freedom to decide on the future directions and projects in my group.
What’s your lab management style? What do you look for when selecting students and staff for your research group?
I consider one of my roles is to suggest interesting research directions to students and postdocs in my group, but in my view developing the project and thinking how to design experiments is the responsibility of every individual researcher. It is extremely important that each person takes the responsibility for the project and engages deeply in its planning and execution. According to this, I would probably be considered as a hands-off manager, and I am happiest when the project works out and the student enters my office with a big smile to show me what they have discovered and how it changes our understanding of the system we are studying. Consequently, I am looking for students who are motivated and determined to embark on difficult and important problems and who are independent enough to collect opinions from different sources but ultimately make their own decisions and take responsibility for the experiments they are performing.
What comes first: technique or biological question?
Although methods development is an extremely important activity in science, my motivation was always to answer key biological questions. Today, to be successful in such studies it is important to embrace the cutting-edge techniques and to employ whichever methodology is most appropriate to answer the question. Therefore, the question comes first and then we do whatever it takes to answer it. Structural biology is a very powerful way of answering many biological questions and considering my aptitude for quantitative approaches in science, over the course of my career I have embraced and applied a range of different methods in structural biology.
Introduction to Nenad Ban’s work
Structural studies in the research group of Nenad Ban on bacterial and eukaryotic ribosomes and their functional complexes, using a combination of crystallographic, electron microscopic and biochemical experiments, have provided fundamental insights into the process of protein synthesis in all kingdoms of life. His group has obtained detailed structural information on eukaryotic ribosomes, which are larger and more complex than their bacterial counterparts. They also obtained a breakthrough in visualizing mammalian mitochondrial ribosomes and on mechanisms of how mitochondrial ribosomes, specialized for the synthesis of membrane proteins, are attached to the membranes. The work of his group on giant multifunctional enzymes involved in fatty acid synthesis offers first mechanistic insights into substrate shuttling and delivery in such megasynthases, with direct implications for understanding of polyketide synthases.
Lab webpage: https://bangroup.ethz.ch/
Two recent papers:
- Saurer, M. et al. (2019) Mitoribosomal small subunit biogenesis in trypanosomes involves an extensive assembly machinery. Science 365, 1144–1149, DOI: 10.1126/science.aaw5570
- Kummer, et al. (2018) Unique features of mammalian mitochondrial translation initiation revealed by cryo-EM. Nature 560, 263–267, DOI: 10.1038/s41586-018-0373-y
More information on Nenad Ban’s plenary lecture at the 2020 FEBS Congress
Nenad Ban will deliver a plenary lecture at the 45th FEBS Congress in Ljubljana, Slovenia on Monday 6th July 2020 on ‘Protein synthesis in eukaryotes: From ribosome assembly to targeting of membrane proteins’: 2020.febscongress.org
Top image of post: Abstract rendering of the extremely remodeled trypanosomal mitochondrial ribosome; created by Marc Leibundgut. These ribosomes feature the smallest known ribosomal RNA complemented by a dramatic increase in protein mass resulting in the most complex ribosomal assembly known to date. Due to the extent of differences, comparison with other ribosomes reveals the most essential, universally conserved, ribosomal elements.