Virginia United/2010/Readings/Responses/UVA/Assignment2

Assignment 2 Responses (Due Jan 27)

Discussion leader: Megan Barron

Engineering Microbes with synthetic biology frameworks

The article discussed some interesting points. I found it fascinating that scientists are trying to standardize a cell by removing the non-essential genes and leaving only the minimal genes required to carry out basic cellular processes. This task presents many challenges given the complexity of biological systems. From last seminar, the article “Five Truths about Synthetic Biology” we were made aware of the difficulties scientists face within the field. For example, the cell’s genome acts in unpredictable ways due to variability in the environment such as, growth conditions, noise, genetic mutations, etc. This creates a problem for the minimal genome project. I was surprised to see the progress made within the field of synthetic biology, everywhere from being able to synthesize DNA, use standardized plasmid systems to the building of promoter libraries. Now, scientists are working on synthesizing synthetic enzymes by using directed evolution and screening techniques. However, they are not always met with success. In summary, the standardization of synthetic parts enhances their integration into biological systems. The field of synthetic biology has evolved from genetic engineering due to the improvements in characterization of biological parts.

Rohini Manaktala 22:51, 27 January 2010 (EST)

Engineering Microbes with synthetic biology frameworks

This article presents many engineering progress on the application of central dogma. Through the modification of DNA sequences, construction of riboswitches, generation of de novo enzymes, and the creation of artificial biological network, scientists and engineers are working very hard on the advancement of synthetic biology. The idea of building a chassis with minimal functions and the concept of genetic/biological/synthetic circuits are fascinating. Yet, they have been puzzling me for quite a while since last Wednesday. This article finally gives me a sense of how those ideas work with synthetic biology. Building a chassis, just as Dan explained in the last discussion, like building a operating system with new softwares, which makes the system more programmable and robust. It is a ideal model to carry out any further experimentation. On the other hand, the concept of genetic/biological/synthetic circuits brings in the idea of putting things together to form a system so that each unit can signal and communicate with each other and perform automated tasks. Synthetic biology, in another words, is the engineering of genetic codes and protein expression.

Yong Y. Wu 23:33, 27 January 2010 (EST)

Engineering Microbes with synthetic biology frameworks

• Specificity of biologically engineered units may make them incompatible with complex natural systems
• Synthetic biology standardizes biological components

Introduction

• Synthetic biology recasts biology into hierarchy of abstractions
  • Parts
  • Devices- combination of parts to achieve single human functions
  • Systems- combination of devices
  • Chassis- Host cells
• Programmability is important for controlling the output of biologically engineered systems. It is a result of well characterized parts.
  • Ties in with the importance of developing well characterized parts discussed in the previous articles.
• Robustness is the consistency of the engineered system.

Disassembling, Constructing, and Rearranging DNA

• Gene introduction to microbes is enabled through plasmids
• Standardizing is the removal of natural sequences not vital to part or system function
  • Activity level need not be preserved but removal of sequences should not abolish target function
• Synthetic biology also incorporates de novoDNA synthesis
• Diverse promoter Library

Engineering RNA Based Control Systems

• Expression of gene targets can be controlled by insertion of antisense strands
• Riboswitches with modified aptamer sequences allow specific binding to certain molecules
  • Disables repression of specified gene activity
  • Creates an ON and OFF switch

Modular Enzyme Engineering

• Generation of new enzymes is important to synthetic biology
• Designing new enzymes can be achieved through modification of existing ones

Redesigning Cellular Networks

• in vitro characterization does not translate to predictable in vivo function
• Use of directed evolution strategies to selected parts of the synthetic circuit
• Standardized parts can improve stability and predictability of engineered networks
• Arjun Athreya 23:37, 27 January 2010 (EST):

Engineering Microbes with synthetic biology frameworks

• This paper focuses on the ability to apply programmability to biological systems.
• It introduces sub-fields of synthetic biology to demonstrate how successful we have been. For example, riboswitches are now a workable tool developed from synthetic biology yet we still require directed evolution to fine tune them.
• Modularity and programming in biology will be limited for a while because parts and devices are context dependent. Practices like DNA assembly have already been standardized but certain processes like the redesign of enzymes will take more effort because we do not understand the principles necessary, for example we do not know exactly how folding takes place.
• One goal is retrobiosynthesis, the redesign of enzymes could allow us to replace organic chemistry with biochem.
• Thad