Cell-free synthetic biology

by Eric Drexler on 12 February 2010

Cork cells, from Hooke’s Micrographia
“Cells”
(Courtesy, Robert Hooke)

Synthetic biology doesn’t require cells, and in several ways, cells are liabilities.

Cells can make engineering difficult. Cell membranes and bacterial walls stand between new genes and the machinery needed to transcribe and translate them. They are barriers to liberating gene products. They contain systems that are complex products of eons of evolutionary history, not systems streamlined to simplify engineering. They are easily poisoned by what would be, to us, useful raw materials and products.

The state of the art in cell-free synthetic biology is already advanced, and moving forward rapidly:

Time and again, decreasing the dependence on cells has increased engineering flexibility with biopolymers and self-copying systems….

Current in vitro methods for synthesizing proteins and evolving protein, nucleic acid, and small-molecule ligands will be improved to accelerate production of new reagents, diagnostics, and drugs. New methods will be developed for synthesizing circular DNAs, modified RNAs, proteins containing unnatural amino acids, and liposomes.


Forster and Church, “Synthetic biology projects in vitro”.

A glimpse of some recent developments:

Cell-free systems offer a unique platform for expanding the capabilities of natural biological systems for useful purposes, i.e. synthetic biology. They reduce complexity, remove structural barriers, and do not require the maintenance of cell viability. Cell-free systems, however, have been limited by their inability to co-activate multiple biochemical networks in a single integrated platform. Here, we report the assessment of biochemical reactions in an Escherichia coli cell-free platform designed to activate natural metabolism, the Cytomim system….


Jewett et al., “An integrated cell-free metabolic platform
for protein production and synthetic biology”.


Networks of productive molecular machine systems need not be packaged in discrete, self-replicating units — not even when they start out that way.


Update, 1 March: changed title for clarity


{ 4 comments… read them below or add one }

Kyle February 12, 2010 at 5:06 am UTC

E.D,

I believe that a confident and active synthetic biology study is the prime gateway into understanding and conducting machine phase synthesis.
We will need synthetic biology systems to create the environments necessary for building the initial tools you wrote about which are the first step towards machine phase.

Here is my experiment that i propose, and the one which i most dearly wish to study.

Can we create artificial biological membranes of arbitrary dimension to hold within them the processes of synthetic biology? This would allow a framework via membrane interaction to localize specific processes and create mechanisms for “feeding” self assembly processes.

Basically, rather then using a “cell culture” to produce some molecule of interest, we have can create an “essentially continuous” membrane.

Eniac February 12, 2010 at 5:57 pm UTC

It is not difficult to produce continuous membranes. Essentially you put a drop of oil on a water surface. See http://en.wikipedia.org/wiki/Langmuir%E2%80%93Blodgett_film for more ideas.

It would be comparably ineffective, though, to host synthetic biology on such, as a 2d membrane has so much less space than a 3d solution. In a cell, the two are comparable because of the small scale, but on any larger scale a solution-based process will always have MUCH higher throughput than one that is surface-bound. Unless you create membranes with high surface area interspersed in solution, such as a colloid, or a bunch of cells. But then, we are talking about cell-free systems here, no?

Kyle February 12, 2010 at 8:13 pm UTC

We will always need a local volume to carry out any reaction. If we have a total volume of 100 cm^3 which is undergoing “synthetic biological processes” of three different types simultaniously or in sequence within the same volume, then we still must contain this volume, least this “anicto-plasm” find it’s members unable to operate.

The matter of cell or not might at this time be arbitrarily given by considering only familiar concepts of cell size for the containment unit. Is the flask not a “cell”?
Thus we are lead to consider that cell might instead be defined by aspects of “membrane” use, or extraneous use of unnecessary functions “secondary” to our prime use. The membrane structures of eukaryotic cells are complex indeed. With a range of different membrane systems in only one “cell”.

In essence what i am suggesting is that a synthetic biology of membrane creation be pursued.

Patrick McCray February 17, 2010 at 8:25 pm UTC

Eric-
Curious if you saw the NYT piece on 2/14 about D.I.Y. synthetic biology and, if so, what your thoughts were about it.

PM

{ 1 trackback }

Leave a Comment

Previous post:

Next post: