Caroline Ajo-Franklin (Harvard Medical School) presented work on a cell-cycle counter.
Steffen Mueller (SUNY Stony Brook) spoke about synthetic virus design.
Live attenuated viruses are usually generated through big serial dilutions in a costly and time consuming process, and the resulting mutations that attenuate it are usually few in number. Instead, perhaps one could attenuate a virus by de-optimizing the codon distribution in its genome (i.e. so that it encoded codons that were rare in the host). Redesigned two capsid replacement cassettes (2643 nucleotides) to maximize de-optimal codons (934 silent mutations). Strangely, the titer of the deoptimized viruses went down, but the number of virions built per infected cell remained roughly the same, suggesting that the changes had actually made them less infective. This is an interesting and exciting approach to attenuating a virus because it is thought that many many mutations introduced would be nearly impossible for the virus to evolve around.
Jack Newman (Amyris Biotechnologies) explained some of the market incentives that surround synthetic biology. He used the Keasling lab's artemisinin work as an example. Malaria kills 3 million+ people per year. Treating it would require something like 500+ million treatments, i.e. 400+ tons of artemisinin, i.e. 600+ tons of Artemisia annua plant material each year. Biological systems can be engineered to produe massive quantities of otherwise costly chemicals, such as artemisinin. He also mentioned Modular Expression Design (MED), which is a paradigm essentially for fast debugging of biocircuits. I wish I had more of the details of it. Lastly, he encouraged all us young, talented, bushy-tailed synthetic biologists to come work at Amyris, which is hiring.
Samantah Sutton (MIT Endy lab) introduced her phosphoregulators (?) for post-translational logic. I unfortunately missed lots of this while finishing the previous entry... more later.
Trevor Swartz (UC Santa Cruz) talked about light-activated LOV-domain histidine kinases.
Interestingly, the LOV domain can be found in many bacteria that have no apparent light sensitivity. Erythrobacter has a 368 bp LOV-HPK that apparently is a light activated histidine kinase, and that a particular sulfide bond seems to be the photosensitive element that alters the kinase activity. Additionally, it is likely that all LOV domains are photoactive.
Brian Yeh (UCSF) thinks that protein based signaling circuits are in many ways superior to other signaling pathways because they operate on fast timescales and ___(?). One problem is ___. Another problem is that the output o one node must act as an input of the subsequent node. "One solution is to use common currencies of biological information." Intersectin is a Cdc42-specific GEF. Fuse PDZ + DH-PH GEF domain + PDZ-binding peptide(?) to make a signaling node with modular input. Yeh built a working proof-of-concept circuit composed of 2 synthetic GEFs in mammalian cells.
Peter Carr (MIT Media lab) & Farren Isaacs (Harvard Medical School) presented an overview of Whole Genome Engineering they called "rE. coli." (Recoding E.coli: rE.coli). So why synthetic genomes? All codons can be (re)optimized and the genome can be made much more stable. A technology platform is under development that employs both bottom-up and top-down techniques to make genome-scale refactoring expedient and practical. Multiplex DNA synthesis and Polymerase Assembly Multiplexing (PAM) can be combined to provide a synthesis technique with throughput on the order of megabases. Polony-based sequencing, DNA error correction, computation tools (genome annotation & analysis, genome sequence parsing, and PAM assembly simulation) and a variety of other techniques are being incorporated into the rE. coli toolbox.