Our research combines synthetic biology with advanced imaging techniques to study problems associated with information transfer at the molecular level in biology:
Synthetic Enhancer Circuits. Deciphering the regulatory code is one of the great challenges of our time. Our approach is to “hack” this algorithm using the tools of synthetic biology. We do this by designing novel DNA regulatory sequences using characterized components, and testing if our “program” displays the predicted regulatory response. At present, this translates to constructing synthetic enhancer elements from the ground up in bacteria, and coupling them to gene circuits to generate increasingly complex modules. In the future, we intend to expand this work to embryos with a long-term goal of developing therapeutic applications.
Genetically Encoded Nanoparticles. In this effort we wish to develop a new class of genetically encoded nanoparticles that will self-assemble from computationally designed RNA molecules and phage-derived RNA binding proteins. These particles will be used for a variety of applications and basic research problems. For example, we intend to utilize these particles with advanced microscopy methods to report interactions of RNA molecules at the single molecule level, and as a result enable quantitative intra-cellular dynamical tracking of RNA and its myriad of biological function and roles. Another application will be to engineer novel Trojan-Horse applications, where particles with a particular type of function will assemble if and only if a set of conditions is detected within the cell, thus allowing us to explore dynamical structure function relations within molecular assemblies. The functions programmed into these Trojan-Horse particles will vary from therapeutics capabilities, to novel small-volume metabolic functions relevant to bio-energy challenges, etc.
1. Amit R “Anti-Cooperative and Cooperative protein-protein interactions between TetR isoforms in Synthetic Enhancers”, J. Comp. Biol., 19 (2012) 115-125.
2. Amit R, Garcia HG, Phillips R, and Fraser SE, “Building Enhancers from the Ground Up: A Synthetic Biology Approach”, Cell, 146 (2011) 105-18.
** Highlighted in: Nature Biotechnology, 29 (2011) 721.
3. Amit R, Gileadi O, and Stavans J, “Direct observation of RuvAB-catalyzed branch migration of single Holliday junctions”, Proc. Nat. Acad. Sci. USA, 101 (2004) 11605-10.
4. Amit R, Oppenheim AB, and Stavans J, “Single molecule elasticity measurements: a biophysical approach to bacterial nucleoid organization”, Biophys J. 87 (2004) 1392-3.
5. Amit R, Oppenheim AB, and Stavans J, “Increase bending rigidity of single DNA molecules by H-NS, a temperature and osmolarity sensor”, Biophys J. 84 (2003) 2467.