Applications and Foundational Technologies for Synthetic Biology
What is Synthetic Biology?
Living cells are truly amazing things. They created the oxygen we breathe and the fossil fuels that power our world. They provided the organic compounds that form the basis of modern drugs and materials. They feed us, live within our bodies, and protect us from other cells and viruses. They can self-organize. They can learn. They are us.
It’s clear that the scope of what biological systems could do is enormous. Among the areas that could most obviously benefit from them are health care, chemical and materials production, environmental remediation, and energy. However, most of the systems that would be useful in these areas are unlikely to occur naturally. We probably won’t stumble upon a naturally evolved cell capable of serving as an artificial blood substitute, for example, or on one that harnesses sunlight as transportation fuel. These systems must be engineered, and the intellectual domain associated with such endeavors is genetic engineering.
Synthetic Biology is a movement within genetic engineering that seeks to convert genetic engineering from what today is a technically challenging art form to something more akin to the more traditional engineering disciplines (civil, chemical, electrical, mechanical, software, etc.) which have well defined tools, approaches, theories, and practices for designing and constructing new works. The central foundation for this new approach is to make the engineering ground-up rather than top-down. Essentially, this means that we begin our engineering with well-characterized model organisms such as E. coli or S. cerevisiae and avoid poorly-characterized organisms even if they show a nascent activity similar to the one we are trying to construct. Into these model organisms we introduce DNAs encoding new biological activities. These systems almost always involve more than 3 genes and are frequently referred to as genetic "circuits". This term is usually reserved for a combination of genes that interact in a dynamic way leading to changes in activity over time. A more general term for these constructs, and the one we adopt, is a "device". Devices can be regulatory circuits, but they could also be biosynthetic pathways, sensor systems, virulence factors or other microbiological-type activities. Devices are constructed from "parts" which are the nonreducible units of biological activity such as ribosome binding sites, gene coding sequences, and promoter elements. Devices can also be nested wherein a higher-order device might be constructed from several simpler devices. Ultimately, the addition of several devices into a cell results in a "system" and hopefully it does something useful.
My lab is developing both applications and foundational technologies for synthetic biology. Currently, we are developing therapeutic bacteria that can be safely injected into the bloodstream, localize to and invade cancer cells within solid tumors, and kill them.
Our work on foundational technologies attacks the principle limitations in our field. Our clearest impediment to progress is the synthesis of the DNA cassettes that represent the "hardware" of our systems. Today, long sequences of DNA can be synthesized chemically by commercial vendors at a cost of $1 per base. Considering that the sequences we design today are on the order of 10,000 bases, and we want to redesign entire four-megabase genomes, the costs quickly become astronomical. Hopefully, the price will drop to an affordable level, but an alternative is to develop a new paradigm based on automated standard assembly of standard biological parts. We are developing such an approach using a combination of robotics and engineered bacterial cells.
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