Prof. Christopher Voigt

Genetic engineering is undergoing a revolution, where next-generation technologies for DNA and host manipulation are enabling larger and more ambitious projects in biotechnology. Automated DNA synthesis has advanced to where it is routine to order sequences >100,000bp where every base is user-specified, the turnaround time is several weeks, and the cost is rapidly declining. Recently, this facilitated the synthesis of a complete 1 Mbp genome of a bacterium and its transfer into a new host, resulting in a living cell. However, while whole genomes can be constructed, the ability to design such systems is lagging. The focus of Voigt's Lab is to develop new experimental and theoretical methods to push the scale of genetic engineering, with the ultimate objective of genome design. This will impact the engineering of biology for a broad range of applications, including agriculture, materials, chemicals, and medicine.

Voigt's Lab is roughly divided into two groups. The first is focused on the development of a programming language for cells. A genetic "programa" consists of a combination of genetic circuits, each of which uses biochemistry to replicate a function analogous to an electronic circuit (e.g., a logic gate). Combining circuits yields more complex signal processing operations. For example, we combined 4 circuits to build an “edge detection program” in E. coli that enables cells to draw the light-dark boundaries of an image projected on a plate. The near-term objective is to develop the foundations by which 20-30 circuit programs can be reliably built. This will require new classes of circuits that can be rapidly connected and are sufficiently simple and robust to be assembled by computer algorithms. We are also developing biophysical models that can map the sequence of a genetic part (e.g., a ribosome binding site) to its function. These models can be used to connect and optimize circuits and programs.

The second group in Voigt's Lab is focused on applying these tools to problems in biotechnology. This encompasses new approaches to old problems (e.g., nitrogen fixation) as well as more futuristic ideas (e.g., re-programming bacteria as a drug delivery device). Currently, we are focused on harnessing the functions encoded within prokaryotic gene clusters. These are contiguous stretches of DNA in the genome that (ideally) contain all of the genes necessary and sufficient for that function. These clusters consist of diverse functions requiring ~20+ genes, including elaborate nano-machines and metabolic pathways. We are applying principles from synthetic biology to rebuild these functions from the ground up, in order to eliminate complex and often uncharacterized native regulation, gain complete control and understanding of the cluster, and to facilitate its optimization and transfer between organisms. To do this, we use the same computational tools, genetic circuits, and construction methodologies developed by the foundational half of the lab. This work represents a step towards whole genome design, where our vision is that the future designer would mix-and-match modular clusters to build a synthetic organism.