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NAKFI Synthetic Biology: Building a Nation's Inspiration: Interdisciplinary Research Team Summaries (2010)

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. "IDR Team Summary 8: What is the role of evolution and evolvability in synthetic biology?." NAKFI Synthetic Biology: Building a Nation's Inspiration: Interdisciplinary Research Team Summaries. Washington, DC: The National Academies Press, 2010.

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Synthetic Biology Building on Nature's Inspiration: Interdisciplinary Research Team Summaries

Fundamentally, the team said it is necessary to develop methods to accelerate evolution to get to a desired result faster, while also developing ways to decelerate or stop evolutionary processes once the experiment reaches an end point.

To do so, biologists and engineers must develop more stable strains of bacteria into which end products of synthetic biology can be transferred or a strain where the mutation rate can be controlled. Ideally, this would prevent the over-mutation or under-mutation (i.e., evolution) of a system, thus making it significantly more reliable and malleable.

In addition scientists must create more robust systems in which swapping of components is seamless. That is, researchers must find a way to share evolved components without reengineering new components for each individual project.

The IDR team also suggested the creation of a universal fitness landscape readout from small molecules that applies across heterogeneous systems. This readout would apply to an overall fitness landscape. A universal fitness readout would simplify matters by allowing researchers to compare evolutionary processes for a variety of applications.

In order to create this kind of generalizability, the team argued that scientists must develop ways to predict and screen for sequences that are consistent with multiple objectives, what they called “multi-objective massively parallel optimization.” This would require the creation of libraries from which scientists could choose components that they know would act in specific, predicable ways in a multitude of conditions.

These suggestions are merely the first steps toward the creation of a more unified practice of directed evolution. Members of the group recognize that many of the processes used in directed evolution experiments are in their technological infancy, but they maintained that additional research might generate the requisite knowledge to create robust yet flexible systems that work in harmony with biological circuits found in nature.

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Front Matter (R1-R14)
Conference Summary (1-6)
IDR Team Summary 1: What new foundational technologies and tools are required to make biology easier to engineer? (7-18)
IDR Team Summary 2: What are the significant differences, if any, between risk assessment capacity and religious analyses of the moral permissibility for synthetic biology applications and other biotechnology applications? (19-24)
IDR Team Summary 3: Reconstructing gene circuitry: How can synthetic biology lead us to an understanding of the principles underlying natural genetic circuits and to the discovery of new biology? (25-36)
IDR Team Summary 4: Designing communities of cells: how do we create communication and collaboration between cells to allow for specialization and division of labor? (37-44)
IDR Team Summary 5: Why are human-designed biological circuits and devices fragile and inaccurate relative to their natural counterparts? (45-52)
IDR Team Summary 6: How can genomics be leveraged to develop coherent approaches for rapidly exploring the biochemical diversity in and engineering of non-model organisms? (53-60)
IDR Team Summary 7: How do we move beyond genetics to engage chemical and physical approaches to synthetic biology? (61-70)
IDR Team Summary 8: What is the role of evolution and evolvability in synthetic biology? (71-76)
IDR Team Summary 9: How do we maximally capitalize on the promise of synthetic biology? (77-82)
Appendixes (83-84)
List of Synthetic Biology Podcast Tutorials (85-88)
Agenda (89-94)
Participants (95-106)