I’m alive again.

Stare at my awesome new PCR machine. And tell me the darn thing isn’t cute. And ignore the carpet from the 70’s it’s sitting on.

It’s been… More than a year since I’ve uploaded anything to this blog. During that time only thing I’ve written long form were occasional tumblr posts dealing with what’s been happening in my life or some dry master plan to rule the universe through the power of science, typical student stuff.

I’ve stopped blogging on this site ever since I started working at Genspace NYC as one of its co-founders and one of the three people who actually did things in the lab instead of talking about biosafety. In retrospect I should have expected to spend a huge chunk of my life helping to plan and run a fully functioning molecular biology lab on shoestring budget, but I never really realized what kind of commitment it would be before it hit me in the face full force. During the heydays of doing projects in the lab I was spending about 12 hours per day running experiments, no weekends, no vacations. And that was while working full-time in other jobs too, since nothing at Genspace paid anything… Well, that’s not strictly true. I did earn enough here and there to get by if I didn’t have to worry about rent and supporting other people, but alas, that’s not the case for me.

Now that I look back at it I feel like I was dreaming for the past three or so years. I dreamt that I was contributing to some pioneering vision, each hour spent while almost blanking out from lack of sleep building toward something greater. Something that might even change the world into a bit more agreeable place. Now, the dream is over. It’s been over for the past half a year, it’s only that I lived in rather characteristically stubborn denial during that time, probably causing some level of annoyance to some of the other Genspacers.

I’ve resigned all my positions at the Genspace NYC lab. I’m not a board member, not an officer, and not a member of the space, though I still have to get all the books and other things I’ve built up in there out. And I think I made the right choice.

Stepping back from Genspace brought me some new perspective, some of which I’m still trying to get used to. Maybe I’ll write about some of the lessons once my head is completely cleared up… I’m still suffering from a bit of a shell shock.  Here’s a short, non-comprehensive list before I forget them later though.

  • DIYbio is not amateur biology
  • Issues of biosafety, a byproduct of initial DIYbio hype being tied to the hype about synthetic biology, completely poisoned good people and good initiatives
  • Despite the biosafety scare no constructive discussion on potential safety and other broader concerns about amateur genetic engineering ever took place. If it did I never heard about it in my three years of genetically engineering e.coli and plants in a warehouse in Brooklyn, some of them involving processes using toxic chemicals -disposed properly, of course
  • Involvement of FBI in reaching out to the DIYbio-amateur genetic engineering community was a double edged sword, in that it helped form a weird perception of hierarchy in some of the people who were in more direct contact with the FBI
  • One of the direct negative results of the biosafety scare and FBI involvement was creation of a group of amateurs whose sole responsibility, in a sense, is to tell other amateurs what to do. Coincidentally those people rarely have any projects under their belt, and are usually not very literate in lab safety practices due to utter lack of experience
  • Considering that no one really listens to above group of people anyway (except maybe reporters, grant organizations and the FBI, none of whom practices garage biohacking, to my knowledge) it’s only served to keep people who had running projects underground due to potential nagging from strangers with no valuable input
  • Despite my comments, I still give high marks to the FBI for deciding not to just tap everybody’s phone. It would have been a waste of their resources, and I view their assessment as very accurate
  • TED conference is the hip rich people’s leadership seminar camp, with some amazing thinkers and respectable individuals thrown in (unlike leadership seminar camps). Still so much better and inclusive than Davos. Perhaps even more effective
  • Maker Faires are what dreams are made of, and more places should have them
  • It’s incredibly easy to put together a minimal molecular biology lab. I just finished putting mine together outside Genspace for about a thousand dollars, including essential reagents. I also helped one of my students put his own together
  • Community lab model doesn’t work as is. Current model assumes new members to be incompetent, in a sense. At least not good enough to work in a ‘real lab.’ And current models drive managers of the community lab to have vested interest in keeping most of the members scientifically illiterate after a certain point, with a few outliers
  • Education should be done by educators. Scientists should provide the materials the educators can work with – reproducibility and clear, comprehensive documentation
  • There are more than a few high schools out there that covers genetic engineering with their students. There are a few that even covers synthetic biology
  • Despite relatively minimal PR, they tend to have worse access to equipment and reagents than most DIYbio/amateur genetic engineering labs, but have better results

I’m definitely missing a whole boatload of important points. I’ll get back to them later when it’s not seven AM with zero sleep last night.

Outside of reflecting on what I’ve been doing for the past three years of my life, I also got a chance to get in touch with and work with lots of interesting people around the city. It turns out that the DIYbio-NYC list I founded couple of years ago was moderator locked after a group vote (that later grew into Genspace) due to potential security issues, and interested people around the city did not have a place to converse about local going-ons with each other. So I just remedied that problem as well.

Here’s a message that went out to people last night:

 

 

Good news, everyone 😉

I’ve just turned off all the moderation settings on the diybio-nyc mailing list, and renamed it biohack-nyc@googlegroups.com 

The list was dead for a while what with everyone needing permission to post on it (which was in place by group decision at the time, what with biosafety scares and all). It was also true that there just weren’t that many people out there who were working on stuff as well. 

Well I’ve been talking to quite a few number of new yorkers out there and things are happening all over the city now. And there has to be a place for people to brainstorm and meet up with each other with a little local flavor. Keeping the list moderated like in the past would have been disservice to the community at large. 

Hopefully this can serve as one of the many springboards available in NYC to help aspiring biohackers learn their trade. 

Spread the word, join up yourself, be excellent to each other and have fun! 

biohack-nyc@googlegroups.com

https://groups.google.com/d/forum/biohack-nyc 

 

 

And yes, I changed the name from DIYBio-NYC to biohack-nyc because

1) as a screw-you to people who are still scared of the term hacker

2)I keep hearing things about the term/group DIYbio that makes me feel like it’s something I can’t agree with.

Hopefully this will begin to attract some brilliant minds that I know are out there to coming out of their genetic engineering closet. And maybe some activity will spur me to write  a whole lot more as a well. God knows I really need to.

edit: before I pass out, I want to go on the record as having said that, despite personal differences, almost everything I know about biology now I learned from Ellen Jorgensen and Oliver Medvedik from Genspace NYC. And I still recommend students and hobbyists go check out the Genspace NYC lab over at 33 Flatbush ave, because, quite frankly, there’s nothing else like it.  

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Barcode the World

I’ve always been curious about DNA barcoding. Interest in wides-scale DNA barcoding exercise had been around for a long time, in part due to potential for amateur scientists to contribute to cause of the sciences using relatively minimal and easily obtained equipments and reagents. There had been some high-profile events and articles involving DNA barcoding techniques applied to everyday life in recent memory, like the infamous ‘sushi-gate‘ incident. Yet how many people really know what is it and how many people have a clear understanding of how to do it? I certainly was clueless for a long time.

It’s a little weird now that I think about it. Despite doing tons of PCR reactions day-in and day-out at the Genspace lab for one reason or another, I never tried  to dig into what exactly DNA barcoding entails in its visceral, barcoded details. Well, recently some of our Genspace members including yours truly went out on a sort of field trip to the Harlem DNA lab (situated within a junior high school in Harlem) for a day-long DNA barcoding workshop in preparation for the upcoming NYC Urban Barcode Project.

And the process couldn’t be easier. In a nutshell it just involved amplifying specific segments of DNA from a sample organism and sending it in to Genewiz for sequencing. The specific DNA segment to be amplified differs slightly from the kind of organism (is it a fish? Plant? Or insects?) but in case of most vertebrate mammals you use a portion of its mitochondrial genome called cytochrome c oxidase subunit I (COI) as the bacoding region. Mitochondrial genome (something I’ve been working with a lot for the past few months, ironically enough) is ideal for this sort of genetic species identification since they hit the exact sweet spot between homogeneity and differentiation within similar branches of the phyla, due to their rate of mutation and how mtDNAs are only passed through the maternal line. If you’re interested in performing your own DNA barcoding experiment outside regular lab settings or any official competition you can do so with the pdf files of requisite primer sequences already online and just order it straight from places like IDT. While specific protocols for running the PCR and prepping samples differ from place to place (I’m still looking for that perfect optimized protocol) what you are doing is a basic PCR amplification of the specific part of the mitochondrial genome, so when push comes to shove I’m sure simple chelex based DNA extraction (crush and pop in the sample with chelex beads for 10 minutes at ~99 C, centrifuge at 13000rpm for about a minute and extract the supernatant) combined with primers and PCR mastermixes or GE PCR beads (which already contain pre-made taq polymerase and buffer mixtures for optimal performance) will work just as well, provided that the sample is fresh enough. I think I’m going to run some experiments with the materials we already have at the Genspace lab and post the results later on. Once we put together a library of verified barcoding primer parts we should be able to do some very interesting projects and classes with the NYC biology community at large.

During the barcoding workshop we had a chance to pick out our own samples and run through the barcoding process with the instructors. I picked regular house ants, some random plant Ellen brought from her garden, and a YFP producing zebrafish that’s been dead for some time (it’s a long story). I went through the DNA extraction, purification, and PCR process outlined briefly above, using appropriate primers (for students participating in the competition the Dolan DNA learning center & Harlem DNA lab will provide the kits for free!). Here’s a picture of the gel we ended up with, dyed with syber-green (thanks Oliver!).

Now I seem to have misplaced the list of what each lane does, but the point is, all the barcoding amplifications worked except for the transgenic zebrafish. And it’s not just me, transgenic fish samples prepared by everyone else failed as well, something I can only attribute to the condition of the sample at the time of the barcoding experiment. You see when living things die cells lose structural integrity and rupture all over the place, mixing existing DNA molecules within the cells with all kinds of junk and nucleases that will damage the sequence. Considering the fish was stinking up to the high heavens by the time we got it to the lab that certainly sounds like a very likely scenario to me.

All the other samples works beautifully, and we prepared about 10ul aliquots of each PCR product and sent it in to Genewiz to get sequenced (the same Genewiz I got my mitochondrial DNA sequence from). They’ll be getting back to use within few days with the sequence data we can feed into public databases of DNA barcodes to determine what kind of organisms they are.

People always talk about how the field of biotechnology is advancing by leaps and bounds, and how the infrastructural developments like massive DNA sequencing centers for cheap sequencing will change how most view life and themselves. For a person not previously versed in biology like myself this was a great opportunity to come face to face with capacity for people outside of traditional academia to contribute to the sciences, using largely off-the-shelf technologies and public databases. The entire process of obtaining the sample, amplifying a specific genome within the sample, and getting it sequenced probably cost me about $5 in terms of materials. Think about that. $5 dollars to gain some level of insight into a genetic makeup of an unknown organism, open to everyone. Although this is nowhere near the kind of stuff we can do with true deep sequencing the day is coming, and it will certainly make for a very interesting world.

If you’re interested in learning more about the NYC Urban Barcode Project or DNA barcoding process in general, feel free to contact me at sung at genspace dot org. Genspace is one of the sponsors of the NYC Urban Barcode Project and we are looking forward to input and participation from students and teachers around the city!

Wings of Genspace

With the Genspace business and other stuff I’m working on picking up steam, it’s getting increasingly difficult to come up with decent enough blog posts these days. I’m still not sure whether this is a good thing or not. I love being busy pursuing my dreams, but writing is about the only thing that’s keeping me sharp, so that worries me a little. Maybe I’m slowly slipping into some state of waking coma…. Either way, I’m doing some really interesting things, so I might as well have a record of some of them here.

Genspace is in full swing, and Ellen’s busy running her biotech crashcourse, with other group-wide projects planned out already. Who would have thought we’d actually have a functioning biotech lab in NYC two years ago? Kudos to the people who stood by us all this time. Just having a lab is not enough though, we’ll be introducing some pretty awesome projects soon, just stay tuned!

I have so many things I want to write about now that I’m finally sitting in front of a computer and logged into my blogging account… But good things need time to mature, like hot pot. So I think I’ll just write about that one thing I’m supposed to talk about in this post 🙂

So we (me and Oliver) are planning to launch a high altitude microbial sampler into the stratosphere and do metagenomic analysis of whatever the samples we can gather from there. Right now I’m thinking of about 25~30km altitude, which should be around temperature range of -50 ~ -20 degrees C, which is really cold but not quite as cold as the furthest reaches of antarctica. Just to give you a scale of how high we’re going, latest version of Boeing 747 has top service ceiling of about 13km altitude. Our device will be flying at or above the double that altitude. Here’s an interesting picture of the Earth taken around 20 km.

Now simply launching a weather balloon into the stratosphere with some minor circuits, GPS and a digital camera would be simple. In fact, if it’s all I wanted I can just walk out there and launch my own balloon-sat right now. Yet, what’s the point in doing what everybody else is already doing, am I right? Now that we have a working biology lab we need to do something to bring my love of space together with my love of biology. Which means microbiome sequencing using samples taken from the above.

You see, there’s practically no real research data on the microbiome of the high altitudes. Considering the resilience of life (if you throw bunch of fruits out into the space from ISS, they’ll survive -kind of) and interlinked atmospheric conditions of the planet as a whole, we personally find it impossible to think that the realm of high altitude is totally devoid of life. There are papers out there tracing back to the era of the cold war suggesting that the maximum height of the planetary biosphere might in fact reach far beyond conventional height, with some evidences suggesting spore presence at mesosphere (~80km).

In order to have at least modestly reliable results from our experiment however, we need to design a device that can remain sterile to and from the stratosphere that will function despite heavy shaking, blistering cold, and falling. So far we’ve been making good headway into design and building of the device (Oliver is practically a McGuyver, with PhD in molecular biology) but it’s been a whole lot tougher than simply throwing together balloons, parachute and a camera that most of these projects tend to do. I’ve accumulated some interesting resources and research results during the course of the project, and will be uploading it to the net soon so that other people can follow in our footsteps and do their own high altitude sampling as well. Maybe it would be possible to grow this into an international program of sorts, considering the nature of the kind of organisms that might be found in the stratospheric range (if we find anything at all).

Recently we launched a simple tethered balloon sat to take pictures of Brooklyn from above. The contraption really had nothing to do with the sampler we’ll be launching, but it still gave us a good feel for what the real launch in the future might feel like.

The balloons were attached to a simple digital camera, a 1.99 semi disposable that took really horrible pictures. I’ll try to find a good one or two and post it later.

We launched the balloon on top of the Genspace building. The weather condition was really great, not too much wind at all. The sunlight was beautiful as well.

I’m one of those kids who used to stay up late at night thinking about the space, the high sky where the deep blue voids split over a thin red line of the sun rising, or setting somewhere over the distant part of the planet. Really, to this day the images still have the power to stir my heart, and make me feel like a human being. This is a meager start but who knows, maybe somebody’s already working on a synthetic biology satellite design that might one day take to the skies 😉

Is it game night yet?

It’s Thursday night. Just one more day to plow through until you reach Friday night with all its movies and drinks. Well, we can’t tell you how to speed up time but we can tell you how to feel like it’s going faster. Play computer games. 

Now, we are talking about Genspace, and we do have a bit of reputation to maintain. So as much as I would like to recommend everyone to get cracking on the battle.net with Starcraft 2 we’ll have to make do with something different; a computer game with science in it.

It’s called Phylo, and you can find it here. Phylo is an entirely browser based (flash based, to be specific. Sorry to disappoint all my iPad toting readers) and doesn’t require any serious computing muscle on the player’s end. I’ve been playing it for the last hour or so, and it’s an odd piece of work. On the surface the game follows some basic rules of pattern matching casual games you might be familiar with like Bejeweled. Yet the experience of playing the game feels far more complex than that, and I don’t necessarily mean that in a bad way. Also, there’s a real benefit to playing this game on your spare time, other than gaining the l33t skills to pwn the n00bs with.

You see, Phylo is ‘a human computing framework for comparative genomics.’ Basically it gives you real multiple sequence alignment problems represented by 4 color blocks scattered on a grid. And of course, budding bio-enthusiasts like us know what’s up when a science programs give us 4 of anything- they represent nucleotide sequences. As you match same colored blocks with each other, you contribute some of your brain power to finding aligned sequences between different genes. If you misalign the blocks you lose a point, and if you create gaps between the blocks (which represent mutation) you lose lots of points. You can gain points by aligning same color blocks on vertical row and you need to gain certain amount of points to pass a level or get another gene to align with your existing sequence. This is a very abstract process of optimization that is usually done with complex computer algorithms and lots of processing power, which would be prohibitively expensive when brute-forced. The authors of the program hope to use the human-computer interaction on a large scale to come up with optimized heuristic pattern.

 

This is how Phylo looks
The logic is sound. After all, usefulness of human ability to find patterns in complex biological simulations have already been proven worthwhile with the fold.it protein folding puzzle game and the Nature paper that came out of it. Guess who’s a co-author of a nature paper.  😉
 

This is how it might look on a scientists’ computer
I’ve played around with the DNA code responsible for idiopathic generalized epilepsy and already 160 other people attempted to solve the puzzle… And 146 people failed. And there lies the problem of biology-turned games. You see, unlike regular puzzle games like Bejeweled or Tetris, not everything will fit together with perfect logical coherency. Granted, there are a few techniques you can use to treat this like any other game (for example, don’t waste your time moving around single blocks in the beginning stages. Crush them together into single group for maximum points in shortest amount of time), but the fact is not everything will fit together and it can be rather jarring for a beginner to figure out what he/she’s doing right, since there isn’t any satisfying feedback to a ‘correct’ sequence formation. It can’t be helped though. This is science, and no one knows the correct answer to detect and give you feedback with. Maybe that’s the whole reason why you should play this game. After all, would you play a match in starcraft with predetermined outcome?
I for one, am looking forward to the future where all games contribute to the discovery of science in some shape or form.

Alan Kay on OOP

Some update before I move on to the main post:

I’m an official team member of the 2010 NYU iGEM team! I’ve learned a ton of biology from Russ, and worked on some cool stuff like visualizing and simulating the Immunoyeast system using Processing language. I’m also working on having a touch-screen installation for the Jamboree, so don’t forget to check it out if you plan on being there.

Genspace is up and running, and it is totally awesome. We collaborated with the BioBus at the World Maker Faire and won the Maker Editor’s Award, which is apparently a kind-of-big deal. I did about 40 DNA extraction, purification, PCR and restriction digest myself, teaching people about basic lab processes and a bit of theory behind genotyping. There were lots of screaming children and spitting involved, but it was totally worth it. The target of the exercise was TASR38 coding SNP, and I should have a detailed post of the whole process up in a few weeks.

There are tons of more stuff I should be writing about, and maybe I’ll find enough time to do that when the iGEM is over (although I’m already thinking about how awesome 2011 iGEM can be).

Back to the main post: I’ve been reading stuff written by Alan Kay again. I think it’s safe to say that he’s one of my all-time heroes by now. There’s a cool book about him and his work called Points of View available for free on the net. It’s not directly relevant to biology or physics, but if you’re interested in education, information abstraction and history it will be a fascinating read.

It’s not that I’m actively seeking out stuff about him. I just seem to run into them whenever I do research for my own projects, whether it be methods for abstracting complex sciences for public consumption or coming up with useful programming tools for beginner’s bioinformatics curriculum.

I was reading up a bit more on structure of Ruby and its use in bioinformatics. I eventually ran into the legendary Ruby hacker _why and his Shoes and Hackety Hack toolkits, which mysteriously led me to another one of Alan Kay’s letters, written in 1998 after OOPSLA. The piece itself isn’t directly relevant to biology. He just talks about how most people don’t really understand OOP in computer sciences and how it’s not really about objects but dynamic messages passed between objects. Here’s an excerpt from the letter I found interesting.

“The key in making great and growable systems is much more to design how its modules communicate rather than what their internal properties and behaviors should be.”

Alan Kay had biology background before he went into computer science and he explicitly stated that his most well-known achievement, OOP model and Smalltalk systems are inspired by biological processes… Which is one of the reasons why I tried to use Squeak Smalltalk system for earlier iteration of my synthetic biology curriculum for high school children (something I’m still working on and need a ton of help with). Considering that earlier versions of synthetic biology in form of BioBrick system is based on core engineering principles I can’t help but to think about possibility of re-applying Alan Kay’s OOP model back to biological systems.

BioBricks based synthetic biology strongly resembles ‘object’-oriented OOP paradigm, where people build parts with unique internal characteristics and then link them together into a whole system. Entire system is focused on functionality of the individual parts with almost no care taken to characterize and document how different parts interact with each other. It should be interesting to imagine a different type of synthetic biology where the biologist considers how different segments of DNA (or perhaps the system should be built on top of larger scale composite parts) modules communicate and work with each other, and how to coerce them into forming larger systems. Systems built on top of message passing rather than minute details of the molecular system.

Sigh, the more I learn about things the more I have to study.

 

EDIT:(Oct/31)

Now you might be wondering why anyone would ever want to worry about implementing true OOP like paradigm or message based system building in biological systems. The answer is simple. All these programming paradigms were created to handle complexity. When we consider that existing paradigm of synthetic biology borrows heavily from that created for engineering and programming computers (one of the prominent figures of synthetic biology, for example, is Tom Knight, of the original MIT lisp hacker fame), ability to handle complexity within engineered framework becomes a fundamentally important issue.

One of the main difference between silicon based computation and that within in-vivo environment is scalability. Conventional programming languages are not very dynamic, and are terrible at scaling up compared to biological systems. If we are to bring any sort of computational/engineering approach to biology we need to address the issue of scalability that works in orders of magnitude difference from initial state. Biological systems do not go through processor bottleneck to transition from one state to another, and they have billions of processes operating in parallel. Engineering and programming approached as we know them will not be very useful for long without efforts to address these issues.

8bit tools of science

According to the founder of Playpower.org, more people in India have TVs at home than tap water. And there are $12 computers everywhere that uses the TVs as monitors, like so many of the personal computers of old.

Now consider that these hardwares based off older 8bit chip designs and the softwares that run on them are more or less in public domain. We are looking at a significant portion of the entire human population just poised on the verge to hackerdom. It’s not just typing education and language training. We could build entirely new framework for education in 3rd world urban area using existing tools of education and science. Imagine being able to design an 8bit program for those machines (some of them can actually do internet) that pulls data from research institutions of all kinds (BLAST, Wolfram Alpha, and etc etc) and scale it down to a form those machines and people using those machines can understand. We already have beta versions of synthetic biology CAD program that undergraduates regularly use for their school assignments and private projects, so it’s not that far away in the future.

Will a child capable of programming computers and pull data on SNP variations to do his/her own genotyping using soon-to-be widely available opensource PCR machines still languish in poverty and despair? I don’t know. I’d sure like to find out though.

Synthetic Biology on KQED QUEST- and some comments on the diybio aspect

(((I was trying to embed the videos from the KQED site directly in the post, but apparently copy pasting embed code in HTML panel isn’t good enough for wordpress. I’ve linked to them instead. They are quite good. You should really check them out.)))

Here are two videos on synthetic biology. The first one is a short introduction to synthetic biology produced by the wonderful people at KQED QUEST program, which goes into some level of detail on what synthetic biology is and what we are doing with it at the moment. Certainly worth some of your time if you’re interested in this new exciting field of science.

The first video is the original KQED QUEST video on synthetic biology.

The second video is the extended interview with Drew Endy available off their website… While the field of synthetic biology in the form we now know and love probably began with the efforts of Tom Knight at MIT, Drew Endy is certainly one of the most active and clear thinking proponents of the scientific field of synthetic biology.

Here is the link to the second video, the extended interview with Drew Endy.

If you hadn’t guessed yet, I’m really big on synthetic biology. I think it’s one of the most exciting things happening in the sciences today, not just for biologists but for mathematicians and physicists in that synthetic biology might one day provide a comprehensive toolset for studying the most complex physical system known to humanity so far… That of complex life-like systems.

I also believe that abstraction driven synthetic biology cannot manifest without a reasonably sized community of beta-testers willing and able to use the new parts and devices within original systems of their own creation. Computer languages like python and ruby needed efforts of hundreds of developers working in conjunction with each other for a multiple years to get where they are today. Complete operating system like Linux took longer with even larger base of developers and we still have usability issues. Synthetic biology must deal with systems that are even more complex than most computerized systems, so it’s not unreasonable to think that we’ll be needing an even wider deployment of the technology to the public and active community involvement in order to make it work as engineering capable system.

So I am a little dismayed, along with legions of other people who were initially excited by the promises of synthetic biology in conjunction with diybio community, to find that access to BioBrick parts and iGEM competition is severely limited against any amateur biology group operating outside conventional academic circles.

You see, unlike computer programming, constructing synthetic biology systems require BioBrick parts from the registry of standard biological parts. Right now it is next to impossible for diy-biologist interested in synthetic biology to get his or her hands on the BioBrick components through proper channels. The DIYBio-NYC group alone had quite a few number of people lose interest because of uncertain future aspects of being allowed access to the BioBrick parts and talking to people from around the world on that issue I’m beginning to think that there are a lot more of such cases. So far the major reasoning behind the restricted access seem to be the safety issue, but considering that the regular chassis used to put together BioBrick parts is based on academic strains of E.Coli that are even more harmless than your average skin cell I can’t see much wisdom in restricting access to the parts on basis of safety.

The bottom line is, the state of synthetic biology and BioBricks foundation at the moment is forcing a lot of people, some of them quite talented, who are enthused about contributing to a new emerging field of science to back down in either confusion or disappointment. Considering that the very structure of synthetic biology itself demands some level of public deployment to stress-test and demonstrate the effectiveness and stability of its individual parts and devices (with creation of those individual parts and devices left to the highly trained professionals at up scale laboratories) this is highly unusual state of affair that is not motivated by science behind synthetic biology. I might even go as far as to say it has the distinct aftertaste of political calculations of public relations kind.

The field of synthetic biology will never achieve its true potential unless the BioBricks foundation and iGEM administrators come up with some way for people outside traditional academy settings to participate in real design and construction of synthetic biology systems.

Here’s a little bonus, the QUEST show producer’s notes on ‘Decoding Synthetic Biology.’

Quorum sensing

Just a quick note on early Sunday morning. 

 

I’ve been reading up a bit on the topic of quorum sensing, which turned out to be a very interesting phenomenon. I’m not qualified to get into the specifics but it’s basically a cell to cell communications method used by bacteria. The mechanism is based on signal molecules and receptors that activate or deactivate certain sets of genes depending on signal strength. The strength of the signal would be determined by the density of the signal molecules within a given area. It means that bacteria (of all kinds I think) have built-in coordination mechanism for group gene expression.  This is news to me. I always thought bacterial behavior was more or less solitary with some mathematical mechanism behind emergence of bacterial colonies, rather than any specific signal mechanism that works to coordinate their behavior as a group. I guess the deeply ingrained eukaryotes/prokaryotes and multicellular vs. unicellular organisms chart from the middle-high school days left its mark on me. The Bassler lab at Princeton University’s department of molecular biology seem to be the leader in the field of quorum sensor studies, something I should definitely check out later. Here’s a TED talk by the lab’s very own Bonnie Bassler on bacterial communication.

This reminds me of a few iGEM project outlines I read on using BioBrick parts to form some sort of macroscopic structure using bacterial components. They all more or less failed as far as I know, but maybe something like that will be possible if we can build a BioBrick based mechanism for controlling quorum sensing mechanism of the E.Coli chassis… Or maybe there’s one in the registry already? I should remember to check it out. Maybe diybio-nyc can build a cellular automata system based on quorum sensing as a demonstration project later on. The prospect of studying complexity mechanics behind the quorum sensing and coordinated bacterial behavior is intriguing to me as well.

I’m also thinking of proposing a simple artificial cell project to the group. From what I’ve been reading the first steps towards building an artificial cell isn’t that complicated as long as we keep the goals modest. For now the goal would be to have DNA replicate and produce proteins within an artificial vesicle.

DIYbio NYC meeting: Apr. 15th

Okay, here we are, the fourth meeting of the diybio nyc group. As you can see the meeting was on the April 15th, almost a week ago, so I’m a little late in writing this post. The week had been a little crazy (I’ve been saying this a lot lately), so I really didn’t have the time to get around to it… It didn’t help that I had a bunch of class works that were already overdue and I had to spend the whole of Saturday and Sunday with bunch of UN/Google/open-source people related to the openeverything conference/bar-camp, which I will have to write about soon.

The April 15th meeting was a discussion meeting wit no lab session involved. It was held in a restaurant downtown called Veselka, an Eastern European restaurant serving some good pierogi (never had one before). While the food was good, the atmosphere wasn’t the most ideal to have a complex discussion though. It’s more of a family place, with lot of people coming and going, everyone talking at rather loud volume and etc. It was a refreshing change of pace from sometimes pretentious NYC food world… But I’m not really about to write a review on the restaurant am I?

The situation worsened due to the fact that a reporter from the New York Times Magazine was planning to show up. Some people in the group had experience with journalists (one of them is a published journalist actually), so we were afraid that something we say might be used out of context. There’s a lot of scaremongering out there in regards to the possible dangers of diybio, and it’s something we really have to avoid at all costs. And then the new members showed up. Total of three. All of them came from very unusual and interesting backgrounds but the venue and the circumstances weren’t very ideal for personal introduction between the old and the new members, especially owing to the fact that the ambient noise was to such an extent that we could not hear people from across the table. I would have loved to talk to them a bit more but didn’t really get much of a chance in between trying to hear what other people were talking about and trying to get actual work done in regards to the mission statement, identity and direction of the diybio nyc as a whole. One of them came from biotech background and I’ve been keeping in touch with him for a while now, through IM and twitter. The other person came from art background, working with a type of bio-art club/collective called the Grafting Parlour, which is kind of like the SymbioticA, pursuing the techniques of biotechnology for artistic pursuits. The last person to show up was from computer sciences background with interest in film making, who seemed a little surprised that she’s the only one with computer sciences background in the whole diybio nyc group (quite frankly that surprises me as well, considering that the whole concept of biohacking came along with the advent of computer sciences and biology’s increased dependence on variety of computerized techniques). I’m afraid that some of us (including myself) might have seemed a little distant to the new members of the group. I will have to try to remedy that somehow later on. DIYbio is about the spirit of openness in science and it would contradict the implicit founding spirit of the group to make new members feel out of place. I’m especially looking forward to talking more about the activities and purposes of the bio-art movement. I believe the whole concept of bio-art itself is replete with incredible possibilities that only art can dare to explore, though the group would have to find a compromise between ethical and scientific constraints and the spirit of exploratory arts… Even finding that fine line between arts and sciences sounds intriguing to me, to be honest.

The basic agenda of the meeting was on drafting the mission statement, establishing the main short term and long term objectives of the group, and finding a way to realize those goal within realistic budget and time constraints. Whenever we talk about doing some sort of project one problem gets in our way. Any biological project of even moderate complexity requires a dedicated lab space that’s not located within residential address. We might be able to pull it off within private residential setting like those people trying to build a bio-lab within their closet, but it won’t do for any long term experiments or groups, since there are just too many legal hoops and hurdles we’d need to workaround. And the last thing diybio as a whole needs in this age of terror-related scare-mongering is questionable legality and dubious safety measures. A member of our group experienced in operation of biotech laboratories is strongly pushing for strong safety protocols comparable to those applied to commercial labs, and I agree with her point. It might sound a little bothersome right now but it will go a long way toward the group being a fully pledged biological lab space.

The problem in obtaining a real lab-worthy space in the city is that it’s just too expensive. We would need a way to raise some funds, by ourselves or with cooperation with other educational institutions in the area like one of our members suggested. We can do a lot of those things if we decide to keep things hush hush and work under the table, but again the risks are just too great. In the nightmare scenario what we do wrong might effect the diybio movement as a whole, pushing the public opinion toward opposition. It’s the group’s implicit agreement that we can’t take that kind of risk at this very crucial time. Compared to finding the space, obtaining real lab equipment is a child’s play, and we’ve already made a lot of progress in that area thanks to one of our member’s generous input.

We need to find a path that would work toward to solving the space issue, and at the moment that happens to be working toward obtaining a legal status for the diybio nyc. It’s our collective belief that having an actual legal identity will help us toward raising funds, cooperating with existing lab spaces, and establishing supply relations with bio-companies we would need to contact in order to get perishable experiment resources. The ideal legal status for a group like diybio nyc would be a registered non-profit, whose tax-exempt status would afford the group with some negotiable leverage when it comes to financial negotiation and support. Drafting mission statement and by-laws for the group would be first step in establishing legal and ideological identity of the group.

All this sounds like a lot of financial and legal talks for a group supposedly dedicated to bringing science to the open. Experiments cost money and requires space, so it can’t really be helped for the moment. At least we do have an actual wet-lab session coming up this Tuesday. It’ll be an experiment to introduce GFP plasmid vector into K12 E.Coli chassis (the E.Coli chassis in this case is completely harmless to human beings. You can actually drink it and it’ll pose no threat to you. It’s a special, non-toxic strain of the E.Coli we all know and fear, that’s been used in laboratories for about a century, as well as variety of high school biology classes). It’ll be a first experiment that would actually allow us to observe and experience the process of introducing plasmid into a bacterial chassis with visible results, so saying that I’m excited about the prospect would be an understatement.

There’s been a lot of trials and tribulations for the group, and I’m sure that there will be more to come. But we are going somewhere with this, and it’s really good to see so many people interested in learning more about the techniques and science of biology outside the traditional medium.

Today’s diybio nyc meetup

I got through another meeting with the diybio nyc peeps. Mostly it was management related talk with what came to be the founding members of the group, in terms of getting legal status and finding space for the group. The biggest problem for the group at the moment seem to be lack of lab-worthy space. Another big problem is finding a suitable project idea for us to go ahead with. Actually, if you ask me the lack of pervading project idea is a bigger problem then the lack of physical space, since lack of project means lack of traction and focus for the group. I would really hate to see the group evaporating due to lack of activity at this stage.

I’m wrecking my brain daily over finding an interesting enough project to proceed with, but so far I’m drawing a blank. The fact that I’m practically ignorant on the deeper nuances of the biological sciences doesn’t really help matters either.

One member of the group had been very generous in providing the group with much equipment and other resources, and the other member is doing much to get to the issue of incorporating the diybio nyc group as a nonprofit. I’m trying to look into the space issue by working with other groups outside of diybio, but I’m not too sure how it will work out… Not a lot of people want to work on unproven projects with unproven people. There is a biotech group within the city that might be able to provide us with labspace and resources but they are about incubating professional businesses which doesn’t sit well with the diybio ethos.

I’m a little embarrassed to admit that sometimes I feel like a third wheel in the group, but I guess everyone feels that way at one time or another when trying to get a meaningful movement going. I will have to remedy it by working harder… I really want to do something significant for the group but I don’t know what I should start with, and I’m getting a feeling that this is a common sentiment shared by many of the ghost members of the group (and yes, there are quite a few ghost members, it’s to be expected I guess).

At the moment all I can do is try to provide more logistical data for the group, like rent, spaces, and possible collaboration with existing hackerspaces to get those things. I guess I can give a bit more info about the S.B. 4.0, there are still whole notebooks of data on that conference. I actually gave then the booklet with abstracts of presentations and posters, I hope it will be of more use to them then it was for me, with their experience with actual wetlab and all…

I am trying to come up with a project idea, though it is more likely that we’ll be going with an idea that more experienced members of the group will come up with. Just juggling through ideas of completed projects isn’t good enough. I need to think about the realistic design and research process that will lead to that finished product, which isn’t easy for someone who still has trouble digging through some of the simpler stuff of molecular biology and pathways. I guess this is time for me to go dig up more igem stuff, and try to make sense of it all in terms of technical execution and practical resource requirements. That is, we won’t be coming up with a model of minimal cell in basement lab anytime soon (as much as I would love to see that happen).

I’m beginning to think about something on the lines of building in light sensitivity into the bacterial chassis (at least I might be able to help out with physics side of things in project like that) but what exactly? What kind of project would I be able to conceive of that incorporates light sensitivity of cells while remaining imaginative and practical within the technical limitations our group face?

E.Coli chassis that follows light? Or avoids light even. Now such idea would be a problem considering that I do not have a very clear idea of the mobility mechanism behind E.Coli (CAN they move? Or will it be a cycle of dying out when within the light rich or deficient environment?).

Considerations like that makes me feel like simply suggesting doing some exercise to make bacteria glow, document the whole process and materials used so that I and other less experienced members of the group can have clearer understanding of the techniques and limitations involved in the process- notably, introduction of foreign plasmids into a native chassis. The plus side of such an approach is that it lays nice groundwork for future experiments for those who aren’t experienced with molecular biology. The negative side would be that such experiment would dig into the resources and time the group doesn’t really have. Possibility of boring more experienced members of the group is also something I need to watch out for. Diybio nyc will not be able to sustain itself without the help of the people experienced in experimental biology.

I just don’t know what to do. Even if I were to suggest the glowing bacteria as a sort of introductory warm-up exercise, we still need to come up with a great project idea at some point.

I’m writing this in the subway on my way home. It’s beginning to sound like the diybio nyc is in some mortal peril now that I read some of the stuff I’ve written. It isn’t. Considering all the odds things are going swimmingly and possibly even better than I first expected. The whole atmosphere of excitement at being able to think about manipulating biology of living systems for academic pursuit is something that makes me feel alive. And I enjoy wrecking my brain over this stuff. It’s only that I’m under constant pressure to do more and get more things done, to make the group really work. It’s because I believe that we have something with potential for some truly wonderful stuff here. And it would be a real shame to let it die out not with a bang but a whimper.