You are on page 1of 3

Rapporteur: Emma Frow

31.10.2008

SB4.0 Roundtable Sessions

Standardization of Parts I — Descriptions & Sharing

This roundtable discussion focused on questions and infrastructure relating to the description and
sharing of standard biological parts. Below is a summary of key points raised during the discussion.
Approximately 30 people attended the session.

I. Terminological confusion

There was reasonable debate about the usefulness of the term ‘part,’ and the distinction between
‘parts’ and ‘devices’ — especially given that one researcher’s ‘part’ can be another’s ‘device.’

• Is a ‘part’ simply a DNA sequence (equivalent to a BioBrick?), or is it a functional object with a


defined input and output? If the latter, does this render it equivalent to the term ‘device’?
Should we avoid using the term ‘part’ and use instead BioBrick or device?

• If it is simply a DNA sequence (including or excluding scars?) would we say that it is the same
part if it is inserted in 3 different plasmids? Is it the same part if it is in different BioBrick
formats? We know that the format can make a difference, in that different scar sites can have
different biological effects.

How much do these terminological descriptors matter? Can we agree on what features are important?

II. Devices and black boxes

At present, the concept of devices seems to be ahead of the science — we don’t have many examples of
easily interchangeable simple parts. Tom Knight stressed that in principle a device should be a black
box, with defined inputs and outputs. Hopefully there is no need to look inside the box. However, it
was pointed out that drawing black boxes around devices does result in the loss of potentially
important information — for example, what happens if one combines two devices containing the same
part/subpart? (risks of recombination, etc.) What information about devices, and about device
compatibility, is necessary to capture?

III. PoBoL — Provisional BioBrick Language (http://pobol.org/)

PoBoL is a minimal, machine-readable format for describing some of the information contained in the
Registry. The initial development of PoBoL came out of the ‘Standards and Specification in Synthetic
Biology’ workshop in Seattle (26–27 April 2008).1

The current goals of PoBoL are to:


• Capture the minimal information needed to describe a BioBrick
• Allow the connection of additional data to BioBricks
• Remain open for extension and interlinking

A brief progress update on PoBoL was provided (see the PoBoL website for details), followed by
general discussion about what information should be included with parts descriptions. Suggestions
raised during the roundtable included:

1
Workshop website: http://www.sys-bio.org/sbwWiki/workshops/standardsandspecifications08.

1
Rapporteur: Emma Frow
31.10.2008

Necessary information / features Currently present in PoBoL?


A standard ‘identifier,’ e.g. doi (to enable ‘tracking’ through literature, etc.) ?
Part classification (possibly into multiple families) Yes
The topology of the interconnection of parts (not just the parts themselves) No
Part compatibility / incompatibility No
Details / map of restriction sites No
Which organisms it functions in ?
Literature references No
IP status of the part and attribution Author and date (but not IP?)
Facility to link to experimental data No
‘Experience’ (a nebulous / ill-defined category) No
Machine-readable format Yes
Interface with CAD ?

(Unresolved) questions included:


• There was lively discussion about whether ‘bench users’ of parts really want or need all of this
information. Is such extensive documentation necessary?
• Should there be a ‘junk’ database that contains any / all information, as well as a more carefully
annotated database?
• What happens when someone modifies a basic part that is a component of several composite
parts/devices?
• Would all this information accompany / be relevant to individual parts, families of parts,
devices? What level of hierarchy is most appropriate? What kind of ‘inheritance’ is there across
levels?
• How do we deal with (indeed, should we bother dealing with) private databases and the
possible need for compatibility across multiple databases?
• What data from the current Registry would be lost if we switched to PoBoL?

IV. Using existing standards

• Could we make better use of existing standards e.g. of the GenBank database?
• What about the simulation and design tools being developed by systems biology groups, e.g. at
Hinxton, EMBL?
• The systems biology community has been developing a Systems Biology Markup Language
since 2000 (http://sbml.org/Main_Page), as well as a Systems Biology Ontology
(http://www.ebi.ac.uk/sbo/) — how much might we be able to adapt from them, or learn
from their experiences?
• And finally, are there things we might learn from existing efforts to create ‘minimal information’
checklists? (e.g. MIAME, Minimum Information about a Microarray Experiment, and MIBBI,
Minimum Information of Biological and Biomedical Investigators, http://www.mibbi.org/). Or
does the engineering approach of synthetic biology preclude the ready adoption of more
biologically oriented tools?

Questions for SynBioStandards Network

1. How do members of the Network feel about the BioBrick / part / device vocabulary?

2. Are there features of PoBoL that you would like to see removed from the table, or additional
features that you feel it would be important to include?

3. Should we be looking to develop closer ties with the UK systems biology community? Would
it be worth having a meeting to learn more about their efforts to develop ontologies and
common data-sharing standards?

2
Rapporteur: Emma Frow
31.10.2008

Standardization of Parts II — Measurements

Session Overview

Again, about 30 people attended this session. Through a series of short talks, the objective was to
continue discussions about the development of measurement standards for biological parts. The talks
provided a good snapshot of the current state of play, but the discussion did not seem to make much
progress or raise many new issues.

Chris Anderson (Berkeley) suggested that the purpose of developing standards for biological parts is
associated with predictive power, aiming to capture something about the function of a particular DNA
sequence. Standards require a theory of use, and in the context of synthetic biology they should help
to minimize the time, cost and uncertainty involved in identifying a sequence associated with a
specific, quantitative phenotype.

Chris described three different models for standards:


(1) Absolute or relational standards (e.g. PoPS, RiPS — this seems to be the dominant model)
(2) Standard analysis (involving the use of algorithms)
(3) ‘Standard sets’ or kits that allow empirical determination of the optimal conditions or
biological parts necessary for the construction of a device with specified function2

Jason Kelly (Ginkgo BioWorks) picked up on the first and third models introduced by Chris, asking
the question of how a distributed community of researchers can make comparable measures of
biological parts. Jason pointed out that only 27 of the 147 promoters currently in the Registry have
been characterized to any extent, and that the measurements provided are incompatible for
comparison purposes. Direct measurement of promoter activity is virtually impossible with current
technology, and the indirect measurements available can be difficult to incorporate into models.

Jason discussed the pros and cons of absolute versus relative measurements of promoter activity. His
promoter measurement kit seems to have resulted in fairly consistent results across the seven
institutions it was sent to, and he suggested that a next step could be the development /
standardization of different ‘approved conditions’ for promoters. It might then be possible to rank-
order promoters according to their relative activities under various conditions, enabling more
informed selection for design purposes. Can design frameworks be built on top of relative
measurements rather than absolute ones?

Kim de Mora (University of Edinburgh) has been working on measuring promoter activity in different
strains of S. cerevisiae. Analysing 13 promoter constructs in 29 different strains, he is now in a position
to construct a promoter measurement kit similar to Jason’s — would the community find this useful?

Discussion

A question that was repeatedly raised during the session was whether the community is ready to
develop accurate, quantitative standards. What incentives could be put in place to encourage
measurement activities for submission to the Registry? And what are effective ways of distributing
standards or promoting their adoption within the community?

In terms of what measurement standards could be most usefully developed at this point, the
following list emerged:
• Promoters
• Terminators
• Toxicity (measure as growth rate? metabolic load? For circuits/multiple genes as well as
individual parts?)

2 The example given was the Crystal Screen Kit produced by Hampton Research

(https://hamptonresearch.com/product_detail.aspx?cid=1&sid=17&pid=1) .