Bio design! Diversity! Selection! Geneticist George Church has a wild side - which includes fantastical pontifications around woolly mammoth resurrection and reverse chirality for supreme virus resistance. He spoke about directed evolution as well as the possibilities of a Human Genome Project 2.0.

George gave us a peek into his intircate world to equip us to address his question; "How do we compete with Darwin?" He refers to the vast amount of time and space for which genetic code has been allowed to evolve through on its own. For his response, let's just say a picture's worth 1000 words:

Theory Work:
In class we discussed the idea of a “Human Genome Project 2.0”, but instead of reading DNA, writing DNA. George Church poses the following questions:

1. If humanity were to undertake such a project, what would be the benefits? What types of new science and engineering would be enabled if we had such a synthetic human genome? Please provide specific examples.
AND
3. Map out a technical strategy for synthesizing a human genome. What technologies would be required? What are existing tools we could leverage? For certain tools that do not exist, what should their capabilities be?

The lesson of the Human Genome Project 1.0, sequencing, was that you should shoot for the moon in the hopes of advance technology far enough to know how to make tools capable of moon shooting. In other words, we set an – at the time- ludicrous goal of sequencing 3 billion bp. After 13 years, $2.7 billion and international collaboration, we had ourselves a reading of the human genome. Yet, the truly invaluable outcome of this project was the acceleration the field of genetics put on the state of technology as a whole.

Andrew Hessle of Singularity University wrote, “The HGP was visionary, initiated even before the first bacterial genome (much smaller) had been sequenced. It transformed biology into a digital information science, yielding ongoing returns that include new insights into the molecular basis of life, cancer, and evolution, and also practical applications, like rapid genetic tests for important diseases."

In the same way, I see the main triumph of a HGP 2.0 is so far beyond the actual synthetic genome. It is the marathon of technological advancements required to print DNA that big, to organize that much and to pack DNA that small. Solving this wicked problem is going to require the ‘Biggest’-Data Scientists and even origami-ists to accompany biological engineers. And it is going to help solve many other real-world problems in the extent that it solves the one we started with. If HGP 1.0 came about with the digital age, HGP 2.0 is our spyglass in which to envision what’s next. We will exceed the speed limits to silicon, we will create the most integrative international collaboration and connectivity platforms, and we will have the data and computational capacity to predict the economy, the environment. From our desire to print 3 billion bp, autonomous and automated machines will be integrated into every aspect of our lives. At this point we will have singularity.

2. Conversely, why might we not want to proceed with such an endeavor? What are the risks?

We will eventually have to entertain the societal and ethical risks of designer babies. People seem to be comfortable with germ line modifications to human embryos for the prevention of disease, but this trails off into the murky water of subjectivity very fast. If genetic disposal to breast cancer is a medical condition worth preventing, then is ADHD or a physical disfiguration? The idea of controlling intelligence or appearance, among other things, immediately points to the idea of optimizing them. Luckily, there is no single variable or metric to rate the vast diversity of types of intelligence, beauty and strength, without homogeny. Thus I hope people will never try.

In the more near term focus, I believe the true risk of DNA synthesis will be data security. Besides coding for the complex protein functions which make up life, DNA can be a platform for digital data storage analogous to the binary our computers today. George Church is familiar with this, as he and Kosuri recently beat the world record in successfully storing 5.5 petabits of data — around 700 terabytes — in a single gram of hardy DNA. To store the same kind of data on the densest hard drives in use today, you’d need 233 3TB drives, weighing a total of 151 kilos. And those probably won’t survive the hundreds of thousands of year that DNA can. (George successfully used around 44 petabytes of data in DNA, immortalizing 70 billion copies of his latest book.)

To paraphrase Sebastian Anthony of ExtremeTech: To foresee a world where biological storage would allow us to record anything and everything, every square meter of Earth could be blanketed with cameras, recording every moment for all eternity/human posterity. If the entirety of human knowledge — every book, uttered word, and funny cat video — can be stored in a few hundred kilos of DNA, though… well, it might just be possible to record everything (hello, police state!)

Images and figures from the MIT Review, the Pew Research Center, Genisyss, ExtremeTech and the Huffington Post.

Professor John Glass works at the J. Craig Venter Institute on a fascinating puzzle worthy only of the most meticulous organizers; the methods to create a minimal genome. As an artifact of coming about organically instead of by a neat and proper ‘programmer’, prokaryotic genomes are hopelessly jumbled, and contain redundancy as well as encoded ‘dark matter’ (currently unknown if it is useful at all). If we could throw out the junk, keep only the DNA required for the most critical functions, and reorder and label everything, you’ve got an ISTJ-type person’s dream cell.

More simple and predictable, minimal cells are important for research and for potential approvals as medical treatments. Currently, Mycoplasma genitalium is being targeted as a model organism, with the smallest genome of any organism that can be grown in pure culture. It has a minimal metabolism and little genomic redundancy. Consequently, its genome is expected to be a close approximation to the minimal set of genes needed to sustain bacterial life.

Using global transposon mutagenesis, John and his group isolated and characterized the genes of M.genitalium. To achieve rapid and large scale genome modification, they have developed a genome engineering strategy that uses a combination of bioinformatics aided design, large synthetic DNA and site-specific recombinases.

The highlight of the lecture was asking about FUGU(!!!), a.k.a. pufferfish. They have the smallest vertebrate genomes yet measured, at ∼400 million bp (eight times smaller than the ~3B bp human genome). For whatever evolutionary reason, it appears that their genome has contracted naturally in the last 50–70 million years, with extreme gene density and nothing extra! In 1993, Nature proposed them proposed as an ideal model organism to study homology to a not yet obtainable human genome. They're also quite exciting to eat!

Evan Daugherty, from the very inspired Wyss Institute for Biologically Inspired Engineering at Harvard University, has helped develop a new technology called in situ sequencing (latin for “in place”). This allows researchers to detect single RNA molecules where they naturally reside—spatially positioned inside biological samples. Oy- In ‘er natural habitat!

Analytic “read” tools span many scales of biology including DNA sequencing (genomics), RNA sequence content (transcriptomics), protein expression (proteomics) and other biomolecules.. The ability to view them simultaneously, mapped along a 3D structural morphometry renders a powerful picture.

“This is really exciting because it’s the first time researchers have been able to look inside cells and see thousands of different types of molecules at the same time.”

Implied applications are that we can make new products that resemble real biological systems; i.e. fibroblast wound healing, understanding how the brain works, and to developing new organoids to further our understanding of biological development.

Among many outstanding things, Nina Tandon is CEO and co-founder of EpiBone, the world’s first company growing living human bones for skeletal reconstruction. She joined us this week to teach on the biomimetic paradigms for tissue engineering.

In practice, this is the design of environments (i.e. bioreactors) that can mimic the settings for developmental biology, so as to grow differentiated tissues in the laboratory. Changing the properties of the bioreactors can result in the grow of different tissue types, from electrical impulses giving rise to cardiac muscle cells to physical motion giving rise to skeletal muscle.

Meanwhile, a fun application of bioreactors for a different purpose: building biotic video games! BWAHA!

Lab Work:
Build a Paramecium/Arduino interface. Measure how fast the paramecia (a) swim and (b) change direction in response to electrical stimulation.

Components (Based off making.do!):

1. toy microscope (4x works fine)
2. eyepiece imager
3. electrode setup: glued 0.9mm pencil leads to a microscope slide at 1cm spacing (and only used two leads instead of four). You can clip aligator clips to the parts of the pencil lead extending past the edge of the slide.

Our special guests arrived in the mail from Carolina: Paramecia, a genus of unicellular ciliated protozoan, widespread in freshwater and brackish environments. Their magic power; galvanotaxis, the directional movement of motile cells in response to an electric field. (ok- it's not that magical..you've heard of moths having phototaxis)

Also, the microscope came. Along with the live paramecia, we had slides with paramecia samples fixed and dyed, so we go a sneek peak of who we were working with. You can see their cilla and oral groove- cute!

We began to build a paramecium playground by modifying the provided vector drawing using CoralDraw and then rastering it out of acrylic using a lasercutter. It took a couple tries.

.

The set up required us to create an electrode along each edge of the 'playground', which would control movement in that direction. As Nina described, it is very important to find a electrode material that does not create paramecium-toxic biproduct with electrochemical degridation, when a current is run through. We used pencil lead, connected with copper tape to our arduino-controled power source .

Finally, we placed our assembled device under a microscrope and pippetted the paramecia onto the center opening. We had unforseen trouble visualizing them because the laser-cutting created a rough surface to the bottom of the well. Thus, the acrylic was not optically clear enough for the microscope to see through. Back to the drawing board!

Here are some example of more developed playgrounds. With visual tracking, they are able to be iphone games.

• GenSpace NYC
• Gaudi Labs
• New Scientist

Also, some sidetracked fun with the toy microscope and our iPhone screens. Who can blame us, it won Best Toy of There Year!

Design Work:
Problem 1: Design considerations for electrical stimulation systems. Below appears an oscilloscope reading for a stimulus waveform from commercial stimulator. When a bioreactor is attached (pink), the stimulus waveform (blue) is no longer faithfully applied.

1. The stimulus waveform is approximately that of a square pulse of 5V amplitude. Describe what happens to the stimulus waveform with the bioreactor attached.
   When the bioreactor is attached, the waveform gets distorted and is not applied correctly to the load. In detail, upon attachment the stimulus no longer reaches the desired 5V, but maxes out at 3V and drops with a significant slope through the stimulation time. Moreover, when the pulse stops, there is a drift towards a negative voltage before the bioreactor's voltage recovers back to zero.
   .
2. Assuming there is a single impedance value for a single bioreactor can you think of an explanation for why the stimulus waveform might be distorted when connected to the load?
   The most reasonable explanation is due to current limitations of the stimulator. By Ohm's law, for a certain impedance we need a proportional amount of current to reach the desired voltage levels. The maximum voltage of the applied field is Im*Z, where Im is the maximum current that can go through the stimulator and Z the impedance of the bioreactor.
   .
3. How might you expect the pink waveform to change if several of the same bioreactors were to
   Having many stimulation chambers connected in parallel would degrade even more the electrical field applied to the bioreactor, as the current needed is adding up for each separate bioreactor.
   .
4. What recommendation for modifying the stimulator would you make to solve this problem?
   To have control over the applied field, you can either reduce the amount of current needed to reach the desired amplitude, by making the stimulus amplitude lower, or lessen the resistance of your bioreactor (e.g. shortening the distance of the electrodes) or, lastly, increase the available current by a higher current rating stimulator or an operational amplifier with high current gain.
   .

Problem 2: Morphological changes associated with electrical stimulation. Below appears Human adipose derived stem cells (hASCs) which were exposed to direct-current electrical stimulation for a period of 4 hours (from Tandon et al IEEE 2009).

1. Using the above images, measure and graph (1) cell length and (2) orientation angle of cells at t=0, 2 and 4 h (use any software you like, I recommend image J software available at http://imagej.nih.gov/ij/). Scale bar corresponds to 200 um and arrows delineate direction of the electric field.
   To use Image J (FIJI), open cell image, change threshold color
   t=0H :: Cell Length = 215.22um ; Orientation angle = -5.57 degrees
   t=2H :: Cell Length = 225.01um ; Orientation angle = -4.32 degrees
   t=4H :: Cell Length = 299.89um; Orientation angle = 3.34 degrees
2. Describe the method used to identify cells (and include image captures at various stages of application of your method). State any limitations of your method, and any potential workarounds should you be able to change the experimental setup.
   We took the average of 10 cells in each image (t=0, t=2, t=4) using the Image J software.

3. Given the role of mesenchymal stem cells in wound healing, state any conclusions you may draw from your above analysis. What other results would you like to see in order to support this conclusion?

Problem 3: Design considerations for perfusion bioreactors.

1. Paraphrase in plain English the worked example on pp 1191-93 in the Ratner Biomaterials chapter. State the assumptions and approximations regarding void volume, fluid velocity, channel geometry. How might you expect these parameters to change over time during bioreactor cultivation of stem cells towards bone tissue?
   
2. Now, examine the below computational models of medium flow through anatomically precise TMJ bone constructs during bioreactor cultivation(from Grayson et al 2009). (A) Color-coded velocity vectors indicate the magnitude and direction of flow through the entire construct based on experimentally measured parameters. (B) Construct is digitally sectioned, and the color-coded contours are used to indicate the magnitude of flow in the inner regions.
   

3. What is the range of velocities experienced by the cells predicted by the model, using the equations from part (a). What issues might you expect with modeling this typeof perfusion system during maturation of geometrically complicated bone tissue for 3 weeks?
   

Biofabrication has taken the nation by storm. Only a week ago, the second-ever BIOFABRICATE summit in NYC showcased a menagerie of organisms, yeast and bacteria to mushrooms and mammalian cells, which have been coaxed into growing disruptive materials of the future.

Fiorenzo Omenetto and Benedetto Marelli, from SilkLab at Tufts University, have long been at this work; unlocking new properties from an age-old biomaterial, silk. They describe, the guiding principle is to reinvent structural biopolymers into high-technological materials through basic principles of materials science, advanced fabrication and ingenuity.

The duo shared their developed method for biopolymer ‘regeneration’, i.e. liquidizing spun cocoons, and reforming into new solids with new uses. The proteins characteristically self-assemble.
In this way, silk can be re-engineered to serve at the interface between the biotic and abiotic world. Optics. Biocompatability. Drug release. Furthermore, the natural origin of biopolymers also allows for the engineering of materials with remarkably low-energy processing and little environmental impact.

From this cocoon:

To this hologram:

Fiorenzo presents silk as a material platform technology! Enumerated forms and applications:

Lab Work:
1. Regeneration of silk fibroin into an aqueous suspension (Refer to Step 1-23 in Rockwood et al. Nature Protocols, 6, 1612–1631 (2011)).

Pre-step! Making Baking Soda (Sodium Bicarbonate, NaHCO3)into Washing Soda (Sodium Carbonate, NaCO3). Heating at 400 degrees does the job to pop off that extra hydrogen.

Cutting cocoons

We boilded the coccoons for 30 min in our 0.02 M Washing Soda solution. This denatures the outer seracin coating that adheres the two fibrion strands together. Thus, a few rinses and drying and we've got a big fluffy knot!

Preparation of the Lithuim Bromide (LiBr) required us to brush off some old stocheometry; also- exothermic, it should be prepared on ice. Next, the addition of LiBr to our tightly packed silk to solubilize the proteins.

During 4 hr incubation, the silk disolves into a golden syrup. We must inject this into a dialysis cassette, and filter via submersion in DI water for 48 hours.

Cleaned up, the biopolymer is ready to rock. It can be poured out into flat sheets (below). It can pick up the fine grooves of a hologram or even loaded into a addative printer.

2. Fabrication of an edible, implantable, biodegradable diffraction grating through soft lithography (please, refer to Step 25H in Rockwood et al. Nature Protocols, 6, 1612–1631 (2011) in background reading).

3. Superfab Assignment - Biomanufacturing in 3D Using the silk suspension obtained in Assignment #1 in combination with a XYZ dispensing system for the 3D printing of silk fibroin

Kevin Esvelt, is a research scientist of the Wyss Institute *(recently inducted as faculty at MIT Media Lab), is a fascinating voice within the burgeoning CRISPR/Cas-9 community. He is outspoken on the technical potential of this newfound genome editing and an even more outspoken on the ethical, political and safeguard considerations surrounding Synthetic Gene Drive. He’ got an itch for ecological engineering.

Gene drive, derived in by Burt 2003in relation to “selfish” genes, occurs when a DNA sequence ensures that is inherited more often than normal. In this case the sequence of DNA can spread itself through subsequent population, regardless of its expense to the organism’s survival or reproductive fitness.

Kevin explains that the synthetic induction of gene drive was not possible until recently.Typically, if a genetically modified organism were released into the wild, little would happen because of the golden rule:
“Because wild organisms have been selected for efficient reproduction in their ancestral habitat, altering them almost always decreases reproduction. Hence, releasing engineered or selectively bred organisms into the wild has little if any lasting impact because natural selection weeds out the human-made changes.”

Survival of the fittest 101.

However he proposes CRISPR/Cas9 genome editing has a distinct ability to build gene drives. If inherited by one parent, it actually ‘reaches over’ to edit the inherited genes of the other parent, to convert heterozygotes into homozygotes which are guaranteed to pass the RNA-guided gene drive to all of their progeny. Wow!

Scary? Consider that the technology has potential to be a much more refined solution than some of the ‘blunt instruments’ we unheedingly use now, with severe ecological impact, like globally toxic chemical pesticides. CRISPR could alter characteristics in animal or insect populations’ that cause them to be agricultural pests or disease vectors, without exterminating them and creating voids in the ecosystem. Insects that think corn tastes icky? Fruit bats with Ebola resistance, anyone? Unintended consequences??

So, CRISPR Gene Drive: risky ecological medalling or a valuable tool in minimizing environmental and man-made problems? When is it applicable- and how.

Creative Work:
What features would you want to see in an online discussion platform devoted to guiding the development of gene drives? Assume that the researchers involved in the project are interested in soliciting public feedback before and during experiments so that they can better identify problems and redesign the technology.
Please give specific examples of already-existing elements – if you want a discussion forum, should it be more like reddit, Quora, or something else? What should moderation be like?
What would it take to get you to regularly participate in such a community?

In the case of a new technology as controversial as CRISPR gene drives, public discussion is extremely important to maintain, but must be well structured and handled delicately. Online discussion boards are notoriously places where the societal norms of sensible dialogue unravel into derisive ‘online comment culture’, spurred by anonymity (They’re science on that.). The simmering international debate over GMO foods creates an intense backdrop for the Gene Drive discussion to enter.

Furthermore, Scientists and the public are going to be challenged to communicate information from their specific spheres to general audience. There are going to be technical as well as cultural challenges in understanding. Scientists are proposing engineered modifications to an infinitely complex environment, which the General Public is ‘immersed’ in. They are actively making assumptions about intended and unintended consequence to the ecological ‘system’, yet may have blind spots or lack resolution that people ‘on the ground’ (i.e. farmers) may be well acquainted with. The platform should level the assigned positions of ‘expert’ versus ‘lay person’, in order to equalize power distribution in dialogue.

I propose a platform that can provide never before seen levels of immersive, interpersonal contact to not only engage scientists and the general public, but also fully contextualize the ‘worlds’ and ’lives’ of the participants involved. If the CRISPR campaign is looking to provide disruptive solutions to farming ecology, there should be equal knowledge and skill transfer disseminating from the daily walks of farmers to the scientists, and not just the other way around.
Thus, I think we can support disruptive technology with disruptive technology. Eyeing the $2B acquisition of Oculus Rift by FB, and Go-Pros- I see an online platform that can support video streaming onto virtual reality piping in from around the world, like a human-network equivalent of the Google Maps vehicle.

Humanized communication engineering for prospective ecological engineering. Crazy- but maybe they have some tricks at the Media Lab to help us out.

Design Work:
Identify a problem that could be addressed using a CRISPR gene drive.
Which organism would you target and how would you alter it? Why is a gene drive a good solution relative to other options?
What could go wrong? Don't go into detail, but list several possibilities. Who should be involved in the discussion of whether to consider this application? Design a basic but evolutionarily stable gene drive that should function in your organism.
The Gypsy Moth (Lymantria dispar) is an important economic pest that causes large-scale damage to agricultural crops, forests, and humans worldwide. That's why it has drawn the attention of olfactory receptor research as a form of pest management. A potential application for gene drives is an olfactory receptor gene suppression that would alter the species odorant binding affinities at a population level to no longer be able to detect its target crop.

Optimally, the gypsy moth can exist in its natural ecosystem carrying out its ecological niche without acting as a pest to agricultural crops. Realistically, a modification like this may create an unfit moth, leading to species supression and major ecological disruption. For one, the Gypsy moth uses its olfactory receptors also for mating, which means that altering the target odorant repertoire could putatively render them unable to detect their mates. Possibly, the gene drive would not be effective, and thus not catastrophic, as by inhibiting mating we are essentially stripping the ability of the drive to be passed to the next generation.

Proof-of-principle experiment
Your goal is to design an experiment that will determine whether CRISPR gene drives can function efficiently in the target organism. Your drive system should not cause population suppression, carry any 'cargo' genes, or change the sequence of any protein produced by the organism. It should only spread itself.

1. Identify a gene that is important for fitness in your target organism. Why must gene drives target genes important for fitness? A literature search may be required. You can use NCBI for information on genes if you wish, though Wormbase is generally superior and easier to use.
   The gene we choose to target is the OrCo gene (sequence shown below from NCBI), which stands for olfactory receptor co-receptor. Knockout of Ors has revealed that OrCo proteins are required for insect olfaction. The gene must be important for fitness because if the gene makes the organism less competitive, then the organism will most likely die before propagating the gene to next generation.
   See Identification and Knockdown of the Olfactory Receptor in Gypsy Moth, Lymantria dispar
   NCBI ::Lymantria dispar dispar odorant receptor OrCO mRNA, partial cds
   .
2. Find CRISPR target sites in the 3' end of the gene using an online tool. For C. elegans and many other organisms, a good user-friendly tool is GT-Scan. Recommended parameters: set the high-speci
   More exotic species require less user-friendly software. For bonus points, use sgRNAcas9, which allows you to analyze any downloaded genome sequence in fasta format. Warning: it's not particularly user-friendly.
   List the relevant criteria for inclusion of each target sequence (e.g. potential off-targets etc) as provided by the program you used.
   THE GENOME FOR LYMANTRIA DISPAR IS NOT SEQUENCED :(
   Hypothetically, if the genome was available we would design the CRISPR target sites based on the sgRNAcas9 software (since this species is not available on GT-scan) -- we run the OrCo gene against the gypsy moth genome and design a GUIDE RNA that does not exist anywhere else in the moth genome. This ensures specificity. Also, it is important to include the target sequence at the 3' end of the OrCo gene.
   Alternatively, we started a new search beginning with a common pest whose genome is sequenced. We found the Fall Armyworm (Spodoptera frugiperda), seen in A draft genome assembly of the army worm, Spodoptera frugiperda. The genome has not been annotated for olfactory receptors, so we ran a BLAST searcha of common known olfactory receptors against the sequenced armyworm. We found around 10 olfactory genes with around 95% match to the armyworm genome. From this data we can then run a GT-scan and design the proper guide-RNA and point of insertion near the 3' end.
   .
3. Would it be possible for you to safely build this gene drive in your current laboratory? Which confinement strategies and safeguards would you use? See Akbari et al. and especially here for recommended confinement strategies.into an aqueous suspension (Refer to Step 1-23 in Rockwood et al. Nature Protocols, 6, 1612–1631 (2011)).
   It is definitely not safe for us to build the gene drive in our current laboratory as pests like Gypsy moth can be found all over the US and can be transferred accidentally on crop transportation. We would need to use use both extrinsic confinement methods (physical barrier, strong air curtains on the laboratory doors, and mandatory inspection of clothing prior to exit) and intrinsic confinement methods (molecular strategies).

Emerging from a crazy week of ecological engineering, our fearless leader, David Kong, accompanied by Sean Kearney from Alm Lab at MIT and Professor Neri Oxman from MIT Media Lab, discuss an **intestinal** track on the human gut microbiota. This is in fact one of the most densely populated ecosystems of microorganisms on earth.

With an estimated 100 trillion microorganisms, the gut is an extraordinarily complex system in which we are beginning to elucidate both microbe-microbe and microbe-host interactions. With plummeting costs for sequencing, we are finally able to closely inspect and confirm correlations of nutrition, disease, and even cognition to the chemo-signals shared with our gut buddy composition.

The gradual adoption fecal matter transplants (FMTs) as a socially acceptable treatment for infectious disease has allowed microbes to emerge as a unique therapeutic in our modern medical world. As a growing fascination, it is also emerging in pop-culture.

Sean and David are involved with some of the newest research on model systems, to both prototype and study complex polymicrobial systems. Their work overlaps with that of Neri Oxman, the designer of a novel wearable microbiota ecosystem.

This technological statement piece suggests a synthetically engineered symbiotic relationship completely unique unto itself; beautifully displaying the mixing of cyanobacteria to harness the energy of light into sugar, with modified E.coli to consume the sugar in the generation of some product for the wearer.

Srivatsan Raman, from University of Wisconsin-Madison, works on synthetic and systems biology, protein design, and the developments of protein science with computational techniques. In fact, he emphasized that if we were to come away from this lesson with one thing, it would be a respect for the shear amount of computational *OOompHF* niomolecular simulations and modeling requires. We did have to leave our computers running all night...

Proteins are defined by their amino acid sequence, and the way they snap up into a folded shape in 3D space. The latter is the major determinant and predictor of protein function (i.e. binding sites, activation sites, etc.). It can be predicted as a lowest energy form, but the inticacies and non-static nature of proteins make this complex, fast.

Computational protein modeling has achieved unprecedented accuracy in predicting protein structures at atomic-level accuracy, making major advances in protein science. Not a minute too soon, because protein databases are filling up with known proteins sequences at a rate faster than we could ever catch up using experimental methods (i.e. x-ray crystallography) to predict structure and shape. These powerful tools can even design proteins as biocatalysts, with new binding partners and self-assembling materials.e. binding sites, activation sites, etc.).

In class, we learned computational methods for modeling protein structures and interactions, including the tools in Rosetta protein modeling suite. It works by creating hundreds of possible folded posibilities and assigning each an energy score. Plodding a slow walk toward the lowest energy form.

Rossetta has its place, but we are also fond of FoldIt, protein folding GAME! (Above.)Computers are good at large scale topology computation, but in all honesty, there is indispensable value to human intuition. This game you can manipulate and fold the proteins with your own hands, while you compete with high-scorers around the world to discover the protein structure!

This week, David Kong spoke about some of the current efforts towards the development of hardware platforms. Synthetic biology requires great hardware. Every synthetic biology experiment utilizes a variety of hardware, from liquid handling systems to centrifuges to culture machines and microscopes.

David presents an interesting incentive to create tools that are open source and accessible. From an industry that is traditionally exclusive to individuals in large institutions that can support high capital equipment, these are big moves. Why? For a more diverse community of 'next gen' syn-engineers. A publication in a sociology journal which David showed us actually demonstrates increased 'innovative breakthrough' from people in the 'outer edge' of a field who bring in more diverse skill sets; especially women.



Some of our favorite syn-biologists hail from from far out places, like Drew Endy from Civil Engineering and comic book land! (...who may or may not have been associated with this shirt, the one time I met him )

David's been working on a Ring mixer Chip : a microfluidic system geared towards making high throughput cloning as tiny, cheap and automated as possible. It is an Arduino system with 32 tiny manifolds of solenoid valves, which are choreographed in different ways to perform four basic functions; (1) fill, (2) mix, (3) incubate and (4) flow – a good start for any biological protocol. The ring where all the action happens is only 15nL in volume! Prototype1 cost +$1000, but hopefully it gets cheaper or I get paid more money soon.

We also enjoyed tales from guest lecturers Julie Legault of Amino, and Will Canine of Opentrons speak about their hardware projects turned start up companies (blasting off or Indiegogo and Kickstarter).

[Amino.ONE], for you to take care of and love in your home.








[OT.One], accelerating and empowering research.