Synthetic Gene Circuits

Cell functionality is a result of myriad interconnected pathways of DNA, RNA, and protein interactions.  While early attempts at cellular engineering were directed by random mutagenesis, rapid expansion of the field of synthetic biology has equipped scientists with the tools to rationally design and alter the basic functionality of genetic networks.  This can be as simple as adjusting the strength of a single network component or as complex as introducing entirely novel non-native pathways.  Synthetic biology approaches to gene network engineering provide unparalleled flexibility and power in their ability to create useful, functional biological systems.  The applications of this technology range from biosensors, to pharmaceutical production, to gene therapy.

Systems Biology of Network Motifs

Biological cells are highly complex systems that achieve high-level goals by distributing labor into simpler tasks completed by different sub-systems.  To work effectively these sub-systems must interface with a network infrastructure capable of communicating goals and regulating actions.  Understanding this infrastructure and its patterns of connectivity is crucial to accurately predicting the behavior of existing infrastructure and in the creation and integration of novel circuits.  By better understanding network motifs, large networks can be reduced to a set of smaller networks.  These smaller networks can be solved in high resolution with a more manageable computational footprint.  Understanding of the motifs also allows us to better construct novel circuits and to integrate them into existing networks.

Genome Engineering

Genome engineering of bacterial provides scientists the tools to produce useful organisms for a variety of purposes ranging from basic science, synthetic biology to production of biofuels. Bacterial posses a unique RNA-guided immune system called “CRISPR”. CRISPRs utilize RNA molecules to guide an endonuclease to a matching DNA target through simple Watson-Crick base pairing. Normally CRISPRs protect cells from foreign, viral, DNA. CRISPRs, however, can be reprogrammed to manipulate DNA and gene expression on the bacterial genome. By designing new CRISPR systems we can create user-designed genomic edits to make novel strains of bacterial and to rationally design new components for synthetic gene systems. 

Molecular Evolution

Nothing in biology makes sense, except in the light of evolution”, as the famous geneticist Theodosius Dobzhansky said. In the post-genomic era, every day we are flooded with massive amount of DNA, RNA and protein sequence data. The only way to make sense of this flood of data is to take the theory of evolution into account. In our lab we are interested in using bioinformatics tools, statistical methods and mathematical modeling as well as evolutionary experiments to study the “imprints” of natural selection on the genes and genomes and reconstruct the phylogenetic networks, to further gain insights into their functional significance and molecular evolutionary mechanisms. Specific research projects include evolvability of signaling circuits, genetic and metabolic networks, forward/reverse engineering of genetic systems and so on.