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.
To see what Hernan has been doing since he left Princeton, please click here.
- Recipient of the 2013 The Society of Biology Award for an Outstanding Biology/Biosciences/Life Sciences Textbook for Undergraduates.