Rebuilding T7

Summary

The rebuilding T7 project is an effort to construct a more modelable version of the T7 genome that we can study. These efforts began with our first designs and testing in T7.1, and are now continuing with the T7.2 project.

People

Leon Chan, Drew Endy, Sriram Kosuri

Motivations

Physical Model to further understand biology

We are interested in questions of how the genetic components of an organism are organized on the genome to carryout functions such as development even in the face of significant environmental variations. However, to rigorously answer these questions, we need to first understand how changes in genome organization lead to changes in the timing and level of gene expression. However our efforts to create empirical computational models based on observations of the primary genetic elements and mechanisms governing gene expression have fallen short of providing system-level predictive capacity. It is unclear whether the differences between our measurements and models are due to our inability to parameterize and simulate the complex biophysical processes involved, or our understanding of the biophysical processes is just incorrect or incomplete. Moving forward, instead of further studying wild-type T7, we can try encoding our understanding of the biophysical processes onto a new genome. We will try to only encode those functions which we understand, while actively removing those that we don't. Differences between the behavior of the engineered and wild-type phage will highlight gaps in our understanding, and will lead to follow-on science.

New Model Organism

On the other hand, our interest in T7 is somewhat arbitrary. If we can construct a better model organism that will let us study hypotheses of how the organization of genetic components make up a biophysical system, it may not be necessary to relate that back to the wild type.

T7 Versions

T7.1 -- Our initial attempt to rebuild the T7 genome.

T7.2 -- A more ambitious effort that revisits some of our initial ideas that were tabled in T7.1.

Publications

Refactoring bacteriophage T7
Nature/EMBO Molecular Systems Biology 13 September 2005 DOI:10.1038/msb4100025
Leon Y. Chan, Sriram Kosuri and Drew Endy
URL PDF reprint News & Views October 2004 version