6:00 PM, Thursday, April 23, 2009
Broad Institute Auditorium (MIT room NE30-1154)
Life with Four Billion atoms
Tom Knight
MIT CSAIL and Ginkgo Bioworks, Inc.
Today it is commonplace to design and construct single electronic components with billions of transistors. These are complex systems, difficult (but possible) to design, test, and fabricate. Remarkably, simple living systems can be assembled from a similar number of atoms, most of them in water molecules. Key ideas of intentional simplification, effective design tools, and stratified designs will help us understand, engineer, and build these simple organisms.
In this talk I will present the current status of our attempts at full understanding and complexity reduction of one of the simplest living systems, the free-living bacterial species Mesoplasma florum. Our recent experiments using transposon gene knockouts identified 354 of 683 annotated genes as inessential in laboratory culture when inactivated individually. While a functional redesigned genome will certainly not remove all of those genes, this suggests that roughly half the genome can be removed in an intentional redesign.
I will discuss our recent knockout results and methodology, and our future plans for:
- Genome re-engineering using targeted knock-in/knock-out double recombination
- Re-sequencing of additional strains of Mesoplasma florum and close relatives
- Whole cell metabolic models
- Creation of plug-and-play metabolic modules for the simplified organism
- Inherent and engineered biosafety control mechanisms
The Knight lab is developing an engineering technology based on biology. The manufacture of complex structures at the atomic scale requires a fundamental change in approach, a shift from physical to chemical processes. Taking effective engineering control over biochemistry allows us to engineer complex atomic level structures with a precision unmatched by any lithographic technology. We believe this capability is the key to cost effective nanoscale fabrication, becoming the dominant manufacturing technology of this century.
Engineering biological systems requires a fundamentally different viewpoint from the science of biology. Key engineering principles of modularity, simplicity, separation of concerns, abstraction, flexibility, hierarchical design, isolation, and standardization are of critical importance. The essence of engineering is the ability to imagine, design, model, build, and characterize novel systems to achieve specific goals. Current tools and components for these tasks are primitive. Our approach is to create standard biological parts, assembly techniques, and measurement techniques. The MIT registry of standard biological parts, in collaboration with the Endy Lab, is a growing collection of DNA snippets containing transcriptional promoters, terminators, protein coding sequences, and specialized components in characterized, documented, and assembly-ready form (parts.syntheticbiology.org). Using these parts, we design, build, and test functional biological systems. To function, these components must be incorporated into a working biological system, a living cell. For most of our current research, this cell is the E. coli K-12 bacterium. With four thousand genes, this cell is by far the most complex portion of the system. Another laboratory effort is a long range project to engineer a simpler chassis and power supply for our systems. We have chosen the simple bacterium Mesoplasma florum as a starting point for this process on the basis of safety, fast growth, and small genome size. We have sequenced the organism in collaboration with the Whitehead Institute, annotated the sequence, and are now working on the reduction and standardization of its genome to perhaps 400 genes, creating a simple, manageable, understandable basis for engineering life.
Tom Knight was recently nominated by the Institute of Engineering and Technology as one of their top 25 most influential figures in engineering and technology today: press release and news article .
This joint meeting of the Boston Chapters of the IEEE Computer and Engineering in Medicine and Biology Societies, MIT Engineering in Medicine and Biology Student Chapter and GBC/ACM will be held in the Broad Institute Auditorium (MIT room NE30-1154). The Broad Institute is on Main St between Vassar and Ames streets. You can see it on a map at this location. The auditorium is on the ground floor near the entrance.
For more information contact Peter Mager (p.mager at computer.org)
Updated: April 10, 2009.