Dicke Fellow and Burroughs Welcome Fund CASI Fellow
Hernan G. Garcia (CV, Google Scholar) obtained a Bachelor’s Degree in Physics from the University of Buenos Aires, in Argentina. He then moved to Caltech where he obtained a PhD in Physics in 2011 working in the laboratory of Rob Phillips. Since 2011 he has been a Dicke Fellow and a Burroughs Welcome Fund CASI Fellow in the laboratory of Thomas Gregor. Starting January 2015 he will be joining the Department of Molecular and Cell Biology at UC Berkeley as an assistant professor in Genetics, Genomics and Development.
Cells, either from a unicellular or multicellular organism, make decisions in response to changes to their environmental conditions and to the decisions that neighboring cells have made. A big portion of these decisions are mediated by transcriptional regulation, the modulation of the level of gene expression of proteins. In the last few years our knowledge of the interconnectivity of these regulatory networks has increased dramatically leading to a hopeful analogy between genetic circuits and electronic circuits.
How far can we take this analogy between genetic and electronic circuits? A look at the diagram of an electronic circuit will allow you to quantitatively predict the output voltage given the input voltage for example. Can we just look at the DNA sequence of a regulatory region and predict the output level of gene expression given the input concentrations of the relevant molecular regulatory players? Answering such questions requires an understanding of the physical principles underlying the regulatory interactions.
At Caltech Hernan tried to realize this strategy of quantitatively dissecting regulation by studying simple genetic circuits in bacteria. Through the combination of in vivo and in vitro experiments and theoretical modeling he dissected a simple regulatory circuit inspired by the lac operon. This was done by systematically varying each one of the relevant regulatory parameters such as concentration of the regulatory proteins and affinity and position of the binding sites for these proteins on the DNA. As a result he showed that, at least in the case of this simple genetic circuit, simple thermodynamic models of transcriptional regulation can reliably predict the output level of expression given the input parameters.
At Princeton Hernan is now addressing the same types of questions in the context of the fascinating process of embryonic development. To investigate these questions he is studying the initial stages of development of the fruit fly Drosophila melanogaster. Understanding development is not just more challenging than regulation in bacteria because of the increased complexity of the regulatory architectures. Development is highly dynamic and developmental decisions need to read out the dynamic inputs and provide a dynamic output in a precise and reproducible manner. In order to quantitatively understand these decisions in the embryo he is developing new methods to look at transcriptional dynamics in full embryos and to dissect regulatory regions in high throughput.
Hernan is also an co-author of the book “Physical Biology of the Cell” together with Rob Phillips, Julie Theriot and Jane Kondev, published by Garland Science.
Physical Biology of the Cell, 2nd edition, Rob Phillips, Jane Kondev, Julie Theriot and Hernan G. Garcia, Garland Science, New York, (2013). (Book website).
- Recipient of the 2013 The Society of Biology Award for an Outstanding Biology/Biosciences/Life Sciences Textbook for Undergraduates.
- Mattias Rydenfelt, Hernan G. Garcia, Robert Sidney Cox III and Rob Phillips: The influence of promoter architectures and regulatory motifs on gene expression in Escherichia coli. PLOS One, in press (2014).
- Thomas Gregor, Hernan G. Garcia and Shawn C. Little: The embryo as a laboratory: quantifying transcription in Drosophila, Trends in Genetics 30:364 (2014).
- Jacques P. Bothma*, Hernan G. Garcia*, Emilia Esposito, Gavin Schlissel, Thomas Gregor and Michael Levine: Dynamic Regulation of Eve Stripe 2 Expression Reveals Transcriptional Bursts in Living Drosophila Embryos, PNAS, 111:10598 (2014).
- Robert C. Brewster, Franz Weinert, Hernan G. Garcia, Linda Song, Mattias Rydenfelt and Rob Phillips: The Transcription Factor Titration Effect Dictates Level of Gene Expression, Cell 156:1312 (2014).
- Press release: An equation to describe the competition between genes.
- Highlighted by Florian A. Karreth et al. in Target competition: transcription factors enter the limelight}, Genome Biology 15:114 (2014).
- Highlighted in Synthetic Biology: Tuning expression by the numbers, Nature Methods, 11:475 (2014).
- Mattias Rydenfelt, Robert Sidney Cox III, Hernan G. Garcia and Rob Phillips: The transcription factor titration effect: Statistical mechanical model of coupled transcription from multiple promoters, Phys. Rev. E 89:012702 (2014).
- Lauren Figard, Heng Xu, Hernan G. Garcia, Ido Golding and Anna Marie Sokac: The plasma membrane flattens out to fuel cell surface growth during Drosophila cellularization, Dev. Cell 27:648 (2013).
- James Q. Boedicker, Hernan G. Garcia, Stephanie Johnson and Rob Phillips: DNA sequence-dependent mechanics and protein-assisted bending in repressor-mediated DNA loop formation, Phys. Bio. 10:066005 (2013).
- Hernan G. Garcia, Mikhail Tikhonov, Albert Lin and Thomas Gregor: Quantitative live imaging of transcription in Drosophila embryos links polymerase activity to macroscopic patterns, Curr Bio. 23:2140 (2013).
- Dispatch by Jacques Bothma and Michael Levine: Development: Lights, Camera, Action - The Drosophila Embryo Goes Live!, Curr Bio. 23:R965 (2013).
- Highlighted in Isabel Lokody: Seeing the pattern, Nat Rev Genetics. 14 (2013).
- Featured in BioTechniques.
- Sarah Marzen, Hernan G. Garcia and Rob Phillips: Statistical Mechanics of Monod-Wyman-Changeux (MWC) Models, J. Mol. Biol. 425:1433 (2013).
- James Q. Boedicker*, Hernan G. Garcia* and Rob Phillips: Theoretical and experimental dissection of DNA loop-mediated repression, Phys. Rev. Lett. 110:018101 (2013).
- Hernan G. Garcia*, Alvaro Sanchez*, James Q. Boedicker*, Melisa Osborne, Jeff Gelles, Jane Kondev and Rob Phillips: Operator sequence alters gene expression independently of transcription factor occupancy in bacteria, Cell Reports 2:1 (2012).
- Hernan G. Garcia and Rob Phillips: Quantitative dissection of the simple repression input-output Function, PNAS 108:12173 (2011).
- Hernan G. Garcia, Heun Jin Lee, James Q. Boedicker and Rob Phillips: The limits and validity of methods of measuring gene expression for the testing of quantitative models, Biophys J. 101:535 (2011).
- Roee Amit, Hernan G. Garcia, Rob Phillips and Scott E. Fraser: Precision computational features in synthetic enhancers, Cell 146:105 (2011).
- Alvaro Sanchez, Hernan G. Garcia, Daniel Jones, Rob Phillips and Jane Kondev: Effect of Promoter Architecture on the Cell-to-Cell Variability in Gene Expression, PLoS Comput Biol 7:e1001100 (2011).
- Hernan G. Garcia, Jane Kondev, Nigel Orme, Julie A. Theriot and Rob Phillips: Thermodynamics of biological processes, Methods Enzymol 492:27-59 (2011).
- Hernan G. Garcia, Alvaro Sanchez, Thomas Kuhlman, Jane Kondev and Rob Phillips: Transcription by the numbers redux: experiments and calculations that surprise, Trends Cell Biol 20:723 (2010).
- Kevin B. Towles, John F. Beausang, Hernan G. Garcia, Rob Phillips and Philip C. Nelson: First-principles calculation of DNA looping in tethered particle experiments, Physical Biology 6:025001 (2009).
- Lin Han, Hernan G. Garcia, Seth Blumberg, Kevin B. Towles, John F. Beausang, Philip C. Nelson and Rob Phillips: Concentration and Length Dependence of DNA Looping in Transcriptional Regulation, PLoS ONE 4(5):e5621 (2009).
- Hernan G. Garcia, Jane Kondev, Nigel Orme, Julie Theriot and Rob Phillips: A First Exposure to Statistical Mechanics for Life Scientists, arXiv:0708.1899v1 (2007).
- Hernan G. Garcia, Paul Grayson, Lin Han, Mandar Inamdar, Jane Kondev, Philip C. Nelson, Rob Phillips, Jonathan Widom and Paul A. Wiggins: Biological Consequences of Tightly Bent DNA: The Other Life of a Macromolecular Celebrity, Biopolymers 85(2):115-130 (2007).
- Lacramioara Bintu, Nicolas E. Buchler, Hernan G. Garcia, Ulrich Gerland, Terence Hwa, Jane Kondev, Thomas Kuhlman and Rob Phillips: Transcriptional Regulation by the Numbers 2: Applications, Curr. Opin. Genet. & Dev. 15(2):125-135 (2005).
- Lacramioara Bintu, Nicolas E. Buchler, Hernan G. Garcia, Ulrich Gerland, Terence Hwa, Jane Kondev, and Rob Phillips: Transcriptional Regulation by the Numbers 1: Models, Curr. Opin. Genet. & Dev. 15(2):116-124 (2005).
* denotes equal contribution