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• MEASUREMENT
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iGEM 2014 Measurement New Track

***The signup deadline for the Measurement New Track has now been extended to the 25th of July. Please also sign up for the Measurement Interlab Study.***

Introduction

Precise measurements lie at the foundation of every scientific discipline, including synthetic biology. The limits of our knowledge are set by how well we can connect observations to reproducible quantities that give insight. Measurement is also an act of communication, allowing researchers to make meaningful comparisons between their observations. The science and technology of measurement are easily overlooked, because measuring devices are so familiar to us, but behind even the simplest devices lies an elaborate infrastructure. Consider a laboratory pipette. How accurate are the volumes it dispenses? How similar is it to other pipettes? How do you know? The answers to these questions are a complex story involving everything from the speed to light in vacuum to the atomic properties of cesium.

In synthetic biology, measurement is a critical challenge that is receiving an increasing amount of attention each year. For example, one of the long-standing goals of both iGEM and synthetic biology at large, is to characterize biological parts, so that they can be more easily used for designing new systems. The aim of the iGEM Measurement Track is to get students informed and excited about these problems, and to highlight the successes that teams are able to achieve in the area of measurement. The Measurement Track also aims to find out what measurement assays teams have available and to lay groundwork for future more complex measurement activities in iGEM.

Measurement Challenges in Synthetic Biology

With all the instruments in our laboratories, why isn't measurement a solved problem in synthetic biology?  Part of the problem is knowing what to measure and in what context.  One way to think about the impact of measurements is in terms of four levels, each building upon the last:

1. Measurement quantifies a phenomenon that has been experimentally observed.
   
2. Quantitative measurements may be used to create a model of how the phenomenon was produced.
   
3. Models may be applied to predict what quantitative phenomena will be observed in a new context.
   
4. Predictions may be used to inform choices about how to engineer towards desired phenomena.
   

Instruments, by themselves, only address the first level.  In synthetic biology, many models are constructed, often post-facto. Quantitative predictions, however, are still extremely difficult: an important part of the problem is determining how measurement relates to context, so that we can understand what sorts of things a model can be reasonably expected to predict.

Even when we know what we wish to quantify, it may be impractical to obtain with our current instruments.  For example, many quantitative models describe how the concentration of chemicals in a single cell changes over time.  Behaviors often vary greatly from cell to cell, so it is often desirable to collect data from a large number of individual cells.  Most current instruments, however, cannot readily measure this.  Instead we end up having to make tradeoffs like these:

A mass spectrometer can measure the amount of particular chemicals in a sample, but any cell measured is destroyed, it is difficult to obtain measurement from individual cells, and often difficult to interpret the massive pattern of data produced to quantify particular chemicals of interest.	A flow cytometer can take vast numbers of individual cell measuremements, but the measurements are of a proxy fluorescent protein rather than the actual chemical of interest and the cells may still be disrupted by running them through the instrument.  Unless calibration controls are run with an experiment, the measurements are relative and non-reproducible.
A fluorimeter is less invasive than a flow cytometer and can measure changing fluorescence over time with little impact on the cells, but still uses a fluorescent proxy.  Its measurements are also of the whole sample rather than individual cells, and also relative to the number of cells in the sample.	A microscope can track and quantify fluorescence from individual cells, but not very many of them, and often needs human help on tracking.

Figure 1: No generally available instrument can measure chemical concentrations in large number of single cells over time.

Relative measurements are a major problem, because they cannot be compared.  If you build models of biological devices using different relative measurements, then you cannot combine the models to predict what will happen when you combine the devices.  If units are relative to a batch of samples or to a laboratory, then you cannot reproduce experimental results: even if two experiments produce the same numbers in a new experiment, if the units are relative you cannot tell whether the results are actually the same or whether they have been uniformly shifted (which might be very important!).

Figure 2: Models using different relative units cannot be compared or connected.  How many "Blue" in the output characterized for Repressor #1 are equal to a "Red" in the input characterized for Repressor #2?

Beyond these core scientific concerns, there are pragmatic problems as well. Instruments are also often very expensive to buy and to operate.  This is an especially big problem for DIY groups and researchers in smaller institutions or developing nations.  Cheaper instruments are sometimes available, but usually produce much less accurate or precise data.  Once you've got the data, you also need to be able to share it effectively, so that everybody can benefit from the information that is being learned.  The community will thus likely also need new tools and data exchange standards to allow for simpler and more effective sharing of measurements and models.

Additional Reading on Measurement and Synthetic Biology

Here are some additional resources that may be interesting and can help you learn more about the lay of the land for measurement in synthetic biology:

Plans for the Measurement Track in 2014

The 2014 event expands on iGEM's long-running inclusion of measurement as a focus area (a measurement award has been given since 2006).  This year we are introducing a medal for measurement, and splitting the single prior award into two awards (Best Characterization Project and Best Innovation in Measurement). Details on these new awards can be found below.

Teams participating in the Measurement Track in 2014 can also earn a Measurement Prize by taking part in a group measurement project (the Interlab Study), in which each team measures the same properties of several known samples.  We will provide some recommendations for experimental and measurement protocols, but teams are encouraged to use whatever approach will provide the most reliable and accurate measurements with the resources available to them.  All of the results will be collected together and later shared, which will allow people to see the tradeoffs between different approaches.

Details

The measurement track offers two separate opportunities for teams:

1. Earning a Measurement Prize: any team may do this, including teams that compete in other tracks
2. Competing for Measurement Track Awards listed below

Earning a Measurement Prize:

In iGEM 2014, the Measurement Track features an Interlab Study, in which teams around the world will measure the same genetic devices in order to determine the amount of variation and reliability of various properties and approaches to measurement. This is not restricted to the Measurement Track teams - any team from any track that participates in the interlab study will earn a Measurement Prize!

Your team does not have to compete in the Measurement Track to participate: teams in any track can participate in the interlab study and earn a Measurement Prize. All teams that compete in the Measurement Track, however, are required to participate in the interlab study.

Any team that participates in the interlab study will receive a Measurement Prize!

Competing in the Measurement Track:

To compete for an award in the measurement track, your team must:

1. Register your team, make a wiki page describing your project, and present a poster and talk at the Jamboree
2. Qualify by participating in the interlab study.

Additional details are given on the General iGEM Requirements and on the Measurement Track Requirements pages.

Awards

Along with the overall Measurement Track Award, there will be two other Measurement Track Awards, Best Characterization Project and Best Innovation in Measurement.

Best Characterization Project:

Careful measurement of a large library of devices is necessary to build a solid foundation for engineering biological systems. This award goes to the team that most advances this goal, as judged by:

• Number of devices characterized in reproducible, non-relative units
• Precision of characterization
• Replicability of results
• Ease of accessibility and portability of results to other laboratories
• Quality of presentation and documentation

Best Innovation in Measurement:

Our ability to characterize the behavior of devices is limited by the assays that are available. Better measurements will be made easier by improvements in how and what we measure, and how we are able to use those measurements. This award goes to the team that best pushes the frontier of measurement capabilities, as judged by:

• Degree of improvement over the state of the art in cost, efficiency, precision, resolution, and/or other relevant capabilities.
• Ease of accessibility and portability of methods to other laboratories
• Quality of presentation and documentation

(Note that Best Innovation in Measurement replaces the prior Best BioBrick Measurement Approach award.)

Requirements

Measurement teams must meet the general iGEM 2014 requirements. In addition, Measurement teams must meet the following track specific requirements:

• Interlab Measurement Study: Details for the interlab study can be found here.
  All iGEM teams are invited and encouraged to participate in the first international inter-lab measurement study in synthetic biology. We’re hoping this study will get you excited for iGEM and help prepare you for the summer!
  

  Please note: All Measurement Track teams are required to participate in the inter-lab study.
  

  All teams who participate in the inter-lab study will be acknowledged at the Giant Jamboree with a Measurement Prize!
  

  For any questions, contact measurement@igem.org.

Medal Criteria

Bronze. The following 5 goals must be achieved:

1. Team registration.
2. Complete Judging form.
3. Team Wiki.
4. Present a poster and a talk at the iGEM Jamboree.
5. Participate in the Measurement Interlab Study
6. Document at least one new standard BioBrick Part or Device used in your project/central to your project and submit this part to the iGEM Registry (submissions must adhere to the iGEM Registry guidelines). A new application of and outstanding documentation (quantitative data showing the Part’s/ Device’s function) of a previously existing BioBrick part in the “Experience” section of that BioBrick’s Registry entry also counts. Please note you must submit this new part to the iGEM Parts Registry

Silver: In addition to the Bronze Medal requirements, the following 4 goals must be achieved:

1. Experimentally validate that at least one new BioBrick Part or Device of your own design and construction works as expected.
2. Document the characterization of this part in the “Main Page” section of that Part’s/Device’s Registry entry.
3. Submit this new part to the iGEM Parts Registry (submissions must adhere to the iGEM Registry guidelines).
4. iGEM projects involve important questions beyond the bench, for example relating to (but not limited to) ethics, sustainability, social justice, safety, security, or intellectual property rights. Articulate at least one question encountered by your team, and describe how your team considered the(se) question(s) within your project. Include attributions to all experts and stakeholders consulted.

Gold: In addition to the Bronze and Silver Medal requirements, any one or more of the following:

1. Demonstrate a substantial improvement over the state of the art in cost, efficiency, precision, resolution, and/or other relevant capabilities of your measurement technique.
2. Increase the ease of accessibility and portability of methods to other laboratories of a new measurement technique of your choosing.
3. Help any registered iGEM team from another school or institution by, for example, characterizing a part, debugging a construct, or modeling or simulating their system.
4. iGEM projects involve important questions beyond the bench, for example relating to (but not limited to) ethics, sustainability, social justice, safety, security, or intellectual property rights. Describe an approach that your team used to address at least one of these questions. Evaluate your approach, including whether it allowed you to answer your question(s), how it influenced the team’s scientific project, and how it might be adapted for others to use (within and beyond iGEM). We encourage thoughtful and creative approaches, and those that draw on past Policy & Practice (formerly Human Practices) activities.

Measurement Track Committee

We have a great committee to help coordinate the Measurement track in 2014.

1. Chair: Jacob Beal, Raytheon BBN Technologies
2. Traci Haddock, Boston University
3. Jim Hollenhorst, Agilent Technologies