CHE.496/2009/Responses/a7

Engineering biology

• Discussion leader:

Thaddeus Webb's Response

A partnership between Engineering and Biology

• To examine how biology and synthetic biology can affect each other and further each others goals.
• Systems engineering claims that large amounts of data and subsequent analysis can replace experimenting but it is better used t o highlight what experiments to do or point out irregularities in known systems.
• systems can be difined as a subset of whole whose interactions with external influences can be easily characterized and usefully analyzed.
• Biology will be important to synthetic biology because it will provide the basic theory.
• Synthetic biology and systems biology intersect in use of extensive modeling and quantification of system. Synthesis and analysis are as divorced from the wet lab as possible.
• Biology would benefit from partnership by adopting engineering culture and practices as well as using tools developed by engineers.
• Engineers benefit from biologist by making use of the basic research and techniques for dealing with organisms developed in biological research.
• This article points out how team members of different backgrounds may be of different use to the team.

Fast, cheap and somewhat in control

• This article points out the need for a standardized design process for biological systems and highlights some obstacles which currently block rapid advancement.
• As knowledge and technique improve, genetic manipulation and domestication becomes faster and more precise.
• So far sucesses are haphazard. Advancement must become more systematic.
• Engineering biology will improve with the expansion of current knowledge. Recognition of the inherent modularity will simplify design.
• The current greatest engineering challenges are lack of infrastructure and tools and an inability to predict how individual parts will operate when part of a complex machine.
• One particular challenge is the parasitic affect of inserted genes. If large portions of cellular resources are devoted to a synthetic function the cell may be adversely affected.
• Evolution is a problem because a deleterious mutation which knocks out the machine will likely make the bacterium more competetive and will allow it to take over a bioreactor.
• Different levels and types of noise can result in complex behaviors.
• This article will help us by outlining challenges that we will need to overcome.

Thaddeus Webb 22:58, 5 March 2009 (EST)

Rohini's Response

A partnership between biology and engineering

Purpose of the article:

• 1) To explain the beneficial outcomes of a partnership between systems biology and synthetic biology
• 2) To understand the quantitative physiology of certain intracellular systems
• 3) To determine the distinguishing attributes of synthetic biology

Synthetic biology:

• 1. Design biological systems to perform a given function
• 2. Verify that the system has the function
• 3. Instantiate the function in DNA code
• 4. Use the system to accomplish the function

Systems biology:

• Definition- in order to understand the behavior of a biological ensemble, one needs to study the whole system rather than isolate the parts making up the system.

Characteristics of Productive Systems:

• a) Have a boundary where variable influences from outside can be ignored
• b) Be able to conduct defined perturbations inside the boundaries that lead to changes in systems behavior
• c) By reasoning generate sensible explanations for the changed behavior
• d) Assess the “goodness” of the system
• e) Evaluate how well the understanding enables predictions of changed systems behavior in response to defined perturbations

Challenges:

• 1. To sensibly describe the inventory of the expression and subcellular/extracellular localization of all mRNAs & proteins expressed by a genome in all the cells of an organism
• 2. To attain quantitative insight into behavior of simple systems on short time scales, such as: developing a method for measuring the number of molecules participating in reactions

Distinguishing Attributes of Synthetic Biology:

• 1. Desire to assemble complex living systems from well-defined parts
• 2. People performing the engineering work call themselves engineers
• 3. Positively emphasize a number of doctoral points from other branches of engineering, (use of interchangeable parts, separation of design from fabrication,abstraction)

Fast, cheap and somewhat in control

Engineering challenges:

• a) Lack of a technology infrastructure- not easy to manufacture /assemble biological parts
• b) Difficult to predict what biological components will suffice

(everything in biology undergoes a change in response to temperature/environmental variations, experiences evolutionary changes)

• c) Difficult to engineer biology to control behavior (mutations, biophysics of reaction network in cells)

The article makes us aware of the present challenges in the field of synthetic biology. Rohini Manaktala 22:02, 6 March 2009 (EST)

Joe's Response

A partnership between biology and engineering

• Article examines the effect of partnering systems biology and synthetic biology .
• There has been a focus on individual parts (molecules) and a lack of systems understanding.
• Certain proposals of systems biology propose that high throughput data would eliminate the need for experimentation.
• Biology will provide basic definitions and theory for systems engineering of biology.
• Productive systems have certain characteristics, including boundaries and responses to “perturbations” (variances) in the system.
• Systems biology and synthetic biology meet at the modeling and analysis of a system.
• A “cross-cultural fertilization” at research sites is needed to promote synthetic biology and advance the field. Members of different backgrounds are important.
• Feedback between engineers and biologists (for systems vs. individual components) is desired.

Fast, cheap and somewhat in control

• Article examines the challenges that will arise when synthetic biology and engineering are combined.
• Engineering uses fundamental theory and known physical properties for the design of systems. However, in biology, the theory may be experimental, the systems may evolve, and the physical properties may not obey “rules.”
• Synthetic biology is unique from the other biological fields in that it attempts to design cellular systems for practical ends.
• A remarkable amount of successes have been found serendipitously.
• Engineering challenges: insufficient tools and lack of technology infrastructure, and the unpredictability of the behavior of individual components in the biological systems.
• System noise contributes greatly to this unpredictability of behavior, as does evolution. --> see bifurcation with the protein kinases.

Joe Bozzay 13:06, 9 March 2009 (EDT)