Targeted kinase inhibitors (TKI) are among the most successful targeted cancer therapies. However, TKIs simultaneously inhibit several human protein kinases, often causing undesirable off-target toxicity. Together with his research group at Berlin Institute of Health, the renowned chemist and biophysicist John Chodera works on increasing the effectiveness of TKIs, making an important contribution to the treatment of cancer. Chodera, who has previously worked at University of California, Berkeley, and Stanford University, is now an Associate Professor for Physiology, Biophysics and Systems Biology at Memorial Sloan-Kettering Cancer Center in New York.
Please close your eyes and think about your research project. What do you see at first?
High-dimensional landscapes are everywhere – energy landscapes of biomolecules, parameter landscapes of machine learning models. Nature learns to deal with stochastic perturbations on these landscapes to produce robust living systems, and we must learn to do the same to produce robust predictive models. Statistical mechanics is the key to understanding all of this.
How would you explain your research to a child?
The human body is made up of a bunch of very tiny machines, so small you can't see them with the naked eye, or even a microscope. But just like big machines like a car can break down, these little machines can also break down. We work on designing tools – just a few atoms in size – that help us repair these tiny machines and make sick people healthy again.
What is it that surprises people when you tell them about your research?
While it sounds tremendously exciting to work with supercomputers and distributed computing and robots to develop new cures for cancer, much of the work is unglamorous: Fixing software bugs, repairing air compressors, dealing with hardware failures. I'm tremendously thankful for the wonderful researchers in my lab who all help share the burden in making sure everything keeps running smoothly while still tirelessly pushing the boundaries of scientific discovery.
With whom would you like to swap your workplace for one day? What would you do?
There is so much I'd love to learn about in other fields and disciplines. I'd dearly love to spend a day in the shoes of another scientist.
Is there any rather unusual hobby or talent you might want to share with us?
Music has always been a central fixture in my life. I have a small collection of musical instruments: single reed, double reed, and brass, some Baroque instruments – including a complete family of recorders, cornetto, and clavichord.
What did your research teach you about life?
Much like in music, research that involves collaborative work as part of a team can be immensely rewarding; playing in an ensemble where everyone works together in perfect harmony can produce something much greater than the sum of its parts.
What would your job be, if not a scientist?
I've always been fascinated by exploration and discovering the unknown. As an undergraduate at Caltech, I was enraptured by the thrill of the NASA/JPL engineers in Pasadena who charted the robotic exploration of other planets or features of our solar system. If not pursuing biology, I'd have loved to be an engineer on one of these projects aiming to reveal new aspects of our solar system and our place in the universe.
Is there any particular object that follows you through work and/or life?
Computers are omnipresent in our work: They run the robots doing our experiments; they allow us to perform immense feats of mathematics to predict which molecules might be good therapeutics; hundreds of thousands of them around the world donate their computing power to the "Folding@home"-project to help us study the molecular mechanisms of disease. They enable everything we do, sometimes in ways so subtle that we almost forget they're there.
Which place in Berlin do you like the most, and why?
I've fallen in love with Mustafa's Döner Kebab in Berlin. Having sampled many examples of Döner worldwide, I can affirm that this is a truly uniquely Berlin culinary masterpiece.
Is there anything about Berlin that you didn’t expect at all? And/or something that you miss here? What makes Berlin special for your research?
I've been coming to Berlin for over a decade, drawn by energetic collaborations with wonderful collaborators at Berlin's many research institutions, including the Freie Universität Berlin, the Zuse Institute Berlin, and the Charité. I had not initially appreciated how much the research institutions in Berlin – and Germany in general – deeply believed in the potential for to have a significant impact on biology and human health. This investment in the transformative power of mathematics in advancing research in biology is something truly unique, and ever more vital to modern interdisciplinary problems in biology and disease.