2020(S09) Lecture:week 8

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Week 8 Tuesday

Challenge: Parts

Part 1: Poetic Parts

This challenge was inspired by This American Life #354: Mistakes Were Made

Consider the content of ‘This is Just to Say” a poem by William Carlos Williams

Poem 1

I have eaten
the plums
that were in
the icebox
and which
you were probably
saving
for breakfast
Forgive me
they were delicious
so sweet
and so cold

The poem is often taught in poetry classes and often spoofed. Consider, for instance, these 2 spoofs by Kenneth Koch:

Poem 2

Last evening
we went dancing
and I broke your leg
Forgive me
I was clumsy and
I wanted you here
in the wards
where I am the doctor

Poem 3

I chopped down the house that you had been saving to live in next summer.
I am sorry, but it was morning, and I had nothing to do
and its wooden beams were so inviting.


And one more spoof from the blog somewhere in the suburbs

Poem 4

I have dried
the shirt
made of 100% cotton
that was on your floor
and which
you were probably
planning
to air dry
Forgive me
if you had sorted
your own laundry
it would not be
so short
and so small

If you wanted to write your own spoof of the William Carlos Williams poem, you might begin by comparing the structure of these four poems. As a starting point they can be broken into 5 elements, namely

  • 2 part situation
  • “forgive me,” and
  • 2 part explanation.

For each poem, these elements are:

Situation (part 1) Situation (part 2) Forgive me Explanation (part 1) Explanation (part 2)
I have eaten the plums that were in the icebox and which you were probably saving for breakfast Forgive me they were delicious so sweet and so cold
Last evening we went dancing and I broke your leg Forgive me I was clumsy and I wanted you here in the wards where I am the doctor
I chopped down the house that you had been saving to live in next summer. I am sorry, but it was morning, and I had nothing to do and its wooden beams were so inviting.
I have dried the shirt made of 100% cotton that was on your floor and which you were probably planning to air dry Forgive me if you had sorted your own laundry it would not be so short and so small

Mix & Match Poetry

Now we can try to swap these poetic elements to see what interesting and clever spoofs we write. How about:

Situation (part 1) Situation (part 2) Forgive me Explanation (part 1) Explanation (part 2)
I have eaten the plums that were in the icebox and I broke your leg Forgive me but it was morning, and I had nothing to do and I wanted you here in the wards where I am the doctor

That seems to work but is it better? Let's try again:

Situation (part 1) Situation (part 2) Forgive me Explanation (part 1) Explanation (part 2)
I chopped down the house and which you were probably planning to air dry Forgive me they were delicious it would not be so short and so small

Well shoot, that's horrible. For one thing: It doesn't say anything understandable---this can be broadly described as a problem of functional compostion. For another thing: the connection between the different elements is, well, "awkward" at best---this can be broadly described as a problem of physical composition. If physical and functional composition of poems were working perfectly then every part would grammatically connect to the ones that flank it, and the meaning of the connected pieces would be interpretable at worst and clear at best.

Part 2: Genetic Parts

The physical and functional assembly of the poetic parts can be mapped to biological engineering once we define what a genetic "part" is. Let's start by extending what we did with the William Carlos Williams poem, namely let's consider a few natural genetic compositions, see what common elements compose them, and then try to bin these so we might compose new genetic elements by mixing and matching parts.

The bacterial lac operon is one we're already familiar with from our conversation with Jon Beckwith earlier in the term.

There are several genes encoded by this composition. LacI is made and we can see it's flanked by a promoter and a terminator. Lac Z, Y, and A are also made and they are flanked by a promoter + an operator on one end and a terminator on the other. So some genetic parts we might consider naming are:

  • promoter
  • operator
  • protein-coding gene
  • transcriptional terminator

Recombinant DNA technology gives us great power to move pieces of DNA around but it doesn't answer all the questions we might have about the resulting composition. For instance, are promoters/operators/genes and terminators all the parts we need to write a genetic program. Would the promoter that's in front of LacI make sense in front of LacZ, Y, and A? Is there something important about the junction of the parts? An introduction to systematic examination and nomenclature of genetic parts, watch Device dude and Systems Sally's introduction to Parts


Part 3: The Registry of Standard Biological Parts

The animation ends with a screen shot from the BioBricks Foundation a not-for-profit organization that "encourages the development and responsible use of technologies based on BioBrick™ standard DNA parts that encode basic biological functions." BioBricks™ represent one kind of standard biological parts, standardized to enable reliable physical composition.

Just as we mixed and matched poetic elements, here are some mixed and matched genetic elements made from BioBrick™ parts.

Image:BBa_I13603.png
Image:BBA-I13521.png
Image:Be109BBa M30010.jpg
Image:BBa_J44011.png

Just as we could identify "forgive me"-ish elements in the "this is just to say poems" we can see common elements in these genetic compositions: the green arrow element which is = a promoter, but which comes in different flavors (I13452, R0040 or R0011), the red stop signs = transcriptional terminators (B0010, B0012).

The part numbers as well as the DNA itself are collected at the Registry of Standard Biological Parts.

For your final project in this class, you will enter a part into the registry. We'll show you some good parts and some good documentation in class so you can model your work on those examples.

Before tomorrow's studio time

If there are outstanding issues related to the system you're working on for your project be sure everyone on your team knows how you'll solve the issue(s) and make a plan to come to studio tomorrow with materials for finishing the system overview and getting good work done on the device list and the timing diagram.


Week 8 Studio

Part 1: better to be lucky than good?

Jonas Salk/Time magazine cover
Jonas Salk/Time magazine cover
Some people seem destined to be in the right place at the right time. There are businessmen, military heroes, and celebrities whose good personal outcomes seem best explained as lucky alignments of stars and planets. Critically good timing was a strength of Jonas Salk, who is commonly credited as the scientist responsible for the polio vaccine. As profiled in Time Magazine, Jonas Salk was "strictly a kitchen chemist (who) never had an original idea in his life," according to Albert Sabin one of "the other" men credited for conquering polio. How can timing be related to cost of launching a project? In Salk's case, his ability to offer a killed-virus as a polio vaccine was wholly enabled by John Ender's discovery of effective culturing techniques for the polio virus itself.

Consider once more the Melbourne 2007 iGEM project. In a series of questions at the end of their presentation, the team gets asked about any changes to the gas vesicles device that might allow gas-filled cells to become even more buoyant. Their answer speaks to some scientific work others have done to understand the vesicle-encoding operon, research that has shown at least one gene in the operon is a negative regulator. By deleting that gene, the Melbourne team thinks they might make their cells even more buoyant. If you and your team were the Melbourne team, what would you do with this information?
Here are some options. You can consider these or others, but weigh them in terms of their associated cost (both time and money).

  • Use the entire gas vesicle operon to get the basic Coliform system working then tweak the system later to improve it.
  • Wait to assemble your system until you can perform experiments to know more about each gene in the operon.
  • Divide the team in half, with some launching into the project with the DNA as is, and others studying it and refining it.
  • Spend one week in the library to read all you can about these vesicles and then decide.
  • Place a DNA synthesis order for the full operon (6 kilobases) as well as every single gene knockout and double gene knockout.

After 10 minutes we will hear back from each group about their preferred strategy for optimizing time and money.

Part 2:

Week 8 Thursday

“Faith is a poor substitute for reason” Thomas Jefferson

As you hone in on the details of your projects, your team should plan ways to validate the system's operation and ways to learn from its glitches. We have two quick challenges for you today. The first illustrates that even the "best" answers you can offer that are consistent with all available data remain tentative, that the answer is either strengthened or revised by additional data and that all interpretations are subject to personal biases, human values and the various ways we all think about the world. The second challenge puts you midstream in a flawed design and requires that you consider the modes of failure to debug/troubleshoot the problem.

We will spend only 20 minutes on these challenges and then you and your team can use the rest of today's lecture time to prepare for next week's Tech Spec Review.
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