Two Great Tastes That Taste Great Together: Professor Hernan Garcia

(Photo by Johnny Gan Chong)

Are the life sciences and the physical sciences separated by fundamental differences? Many biologists and not a few physicists think so: the processes and materials of life are too murky, too overdetermined, too intertwined, to be teased out and reduced to testable rules with predictive power. Physics is clean, clear-cut, and containable. Associate Professor Hernan G. Garcia has been doing research that bridges those differences and aims to clear our understanding of life’s basic building blocks by applying the intellectual framework, tools, and analytical techniques of theoretical physics to cellular development. 

Professor Garcia holds a joint appointment in Genetics, Genomics, and Development in the Department of Molecular & Cell Biology and in the Department of Physics. His lab space is in the life science buildings but in nine years at UC Berkeley he has never had an MCB grad student – they have all been from Physics or the Biophysics graduate group. He jokes that PhD students from his group serve as the Trojan horses that bring physics perspectives into bioscience spaces. 

As an undergrad in Buenos Aires, Garcia did a research internship in quantum opto-electronics and imagined that he would take up a theoretical physics career in string theory, as one does. But quantum optics is just a zig away from biological imaging, and this set him off in the direction of cellular development. He found that it’s the unsolved biogenetic puzzles that are pushing the bounds of science in our day. Particle physics problems are fascinating, for sure, but they are containable, they stay put, where biological problems are still challenging to pin down. And biophysics problems can have shorter cycles of theory and experiment such that a graduate student can go around the track himself once or more, whereas particle physics research is more of a relay race.

(Photo by Johnny Gan Chong)

With his theoretical physics background, Professor Garcia is a proponent of the proof-by-synthesis approach, the notion that true understanding of a system requires the ability to rationally design it from the bottom up without resorting to an “enlightened empiricism” approach of repeated cycles of trial and error. He is starting to develop a unified account of how genes are regulated. The public has heard that only about 2% of our DNA codes for proteins. What is the rest of it doing? ‘Junk DNA’ is a false expression, insists Garcia. He doesn’t use it. Better to just say ‘non-coding’ DNA, because it is key to the timing and the interactions of all those other proteins – to their development into an organism. Consider embryonic stem cells: when they grow up, they differentiate into brain cells and skin cells and liver cells and so on. Geneticists discover that that development is controlled by an intricate network of genes turning on and off in a regulated fashion, and they can construct maps that illustrate the process. 

Maps show you what is there but not how it was built. That requires a wiring diagram and the equations, the mathematical descriptions, of how these cells become fingers while those become your brain. To take on this job, Garcia’s lab applies techniques historically used in theoretical physics. That is a pretty good definition of biophysics: the application of tools and techniques from physics to solve research questions in biology. Biophysicists aim to balance the tension between models that are mathematically tractable and models that accurately explain reality—life’s messiness. 

More specifically, by applying statistical mechanics to carefully collected data from the embryonic development of well-known experimental subjects like fruit flies, Professor Garcia improves the developmental models, moving the field from maps towards more of a recipe guide. This could pave the way for potential future applications, such as programming cells to achieve precise functions for bioengineering purposes in areas like farming or medicine. 

Professor Garcia is optimistic about the future of research in embryonic development. “There’s this idea that biology is too complicated to predictively understand, and that there’s something akin to magic in the ultimate functional complexity of biology,” he notes. “I think that’s a bit of a defeatist argument; with the right tools and the right mindsets, we can attack the question of complexity and start making sense of all the chaos.” 

There is a strength to this faith in both nature’s comprehensibility and science’s power that comes out in both Garcia’s enthusiasm for teaching and his perseverance through difficulties. Every August he runs a physical biology bootcamp for incoming students interested in MCB, biophysics, and computational biology. The objective of this bootcamp is to introduce students to biological numeracy and the physical modeling of biological phenomena. “Professor Garcia has reached out to community colleges to help enhance the research environment for under-resourced students, participated in the L&S Emerging Innovators in Biology symposium bringing rising stars in post-doctoral status to opportunities for faculty positions at UC Berkeley, and also brought out the 2nd edition of his now classic textbook on the physics of Biology," commended Michael Botchan, former Dean of the Biological Sciences Division. He redeveloped MCB 137L into a new attraction – the Physical Biology of the Cell targets upper division and graduate students, and he solo teaches the course each spring. “I love working with graduate students particularly, because they are at a point in their academic careers where they can and should be taking risks,” beams Professor Garcia.

Theory and experiment reinforce each other and move our knowledge about, and our command of, the living world all around us forward. Like many other UC Berkeley faculty, Hernan Garcia is proudly invested in his area of study and how it contributes to basic science discovery. He is alert to potential applications and advantages that his physical research on embryonic biology may develop, but his core goal is to advance physical biology itself in the expectation that with the right tools and enough good data, we can lift the world. 

(Photo by Johnny Gan Chong)