Too Much Information (EW OMG TMI)

This week was truly centered around the discussion with the experts, and with good reason: the experts facilitate research and progression to an astonishing extent. We went from thinking about a species of cyanobacteria and devices within it to considering an entirely different genus, Vibrio, and its applications in the gut of a fish. That's a huge shift in the focus of our project, and considering how deep we are into the semester, it's a little concerning.
As resourceful as the experts were, (and they really were, we have tens of pages to prove it) I feel like it was too much information!! Well, I'm exaggerating a little, as there's never too much information when creating an engineering project based off of the research of other people, but I still feel overwhelmed. This fish gut idea is cool and Natalie likes it, but can we really pull it off?
We're going to have to identify a species that'll function the best in this unfamiliar genus territory, characterize everything it'll need to thrive in the ocean or the gut, identify devices and parts to augment it's decomposition functions, and have something comprehensive to present in two weeks. Can we do it? Then again, were we that far advanced in our research of cyanobacteria? Well for one, we knew there was a near-fluent parts transition between our former e. coli concept and cyanobacteria, but what now?
Our group has taken nothing off of the table as of yet, and we still have to consult the cyanobacteria expert on Tuesday.
I wish I had a way to gauge our progress against some kind of standard, so we could know if we were on track for presentations or a little lacking. That would be supremely comforting.

Experts! Ideas! Microplastics!

This week, we had the chance to talk to a couple of experts about our project. The first was an expert on the ocean ecosystem. She agreed that engineered cells might be able to mitigate the plastic pollution in the ocean, but she was quite concerned that the strategy would create a new problem. I suppose that's true, but the current pollution is literally killing everything in the ocean. Perhaps our project might disrupt the ecosystem, but at least there would be an ecosystem left to protect afterwards.

The second was an expert on using marine bacteria to degrade plastic. He was a) very enthusiastic and b) funny! Good to know scientists like him still exist! He told us about how the natural microbes degrading plastic might actually be bad for the environment, because they create so many microplastics. He also suggested some cool ways to make existing plastic more biodegradable, by adding trace nutrients like phosphorus, nitrogen and iron. However, I thought the coolest thing was all the work he has done studying the top micron of the ocean, and the plastic which acts as an extension of that. The bacteria up there have some really clever ways to adhere to and thrive on plastic!

So I think we need to make sure our project focuses disproportionally on microplastics, because we don't want to be generating more microplastics than we degrade. We also might need to move away from polystyrene, because it seems to degrade in UV light anyway.

The second expert also mentioned that microplastics seem to accumulate in fish and marine life. I had a crazy idea: what if we used the "E. Coli of the sea" to degrade plastics inside fish? The plastics would already be accumulated, and we would hopefully save a lot of fish from a death by plastic. Plus, the fish can do all the mechanical work of gathering plastic and expelling products of degradation, so we can just focus on the chemistry!

2 Phone calls and 99 Problems

When we were on the phone with the Wnt signaling expert, I was actually impressed at how our circuitry was withstanding his review. Initially, I was certain the whole thing was going to fall apart, but actually our circuitry did a pretty good job. Then suddenly wrenches came flying out of nowhere into our project. Apparently stem cells, naturally have high levels of Wnt as a natural part of their development. So while our circuitry detected cancerous cells, it also was going to produce a false positive for all stem cells. Several times now we’ve learned something in 7.013 and then applied it in lecture the next day. Professor Sive has yet to disappoint. Thanks for Professor Sive, we just learned all about stem cells in lecture. According to Professor He, the stem cells and cancerous cells are nearly indistinguishable, so we certainly have our work cut out for us. Somewhere we plan on starting tomorrow is that stem cells uniquely divide their mitochondria asymmetrically. In order to do this there must be some transcription factor or unique signal cascade being produced somewhere.  We plan on taking advantage of this and setting up a detection mechanism for this unique factor and finding out what exactly this factor is to help us see if a given cell is really cancerous or if it’s just a stem cell being mistaken as cancerous.

When we were talking to the virology professor, he didn’t seem to optimistic about using our EBV virus. He didn’t seem overall pessimistic about our project, which is at least a sign of hope. He gave us a couple of suggestions that will definitely help to guide us along in our hunt for the optimal vector.

I know I started out the course by saying I was truly hoping we would get to produce something unique and meaningful, and it seemed like it might not be possible to do something like that after our talk with Professor He. Our one shining ray of hope lies in whether or not we can sense the difference between stem cells and cancerous cells. If we’re able to do this and make our project an overall success, we might be able to produce a meaningful project.  While it’s extremely unlikely we will be able to make a legitimate contribution in the field of cancer detection, I would be extremely honored to know I helped inform doctors earlier of even a few cancer patients’ condition. To know that I had a meaningful impact on someone’s survival would be incredible. One day when I have more expertise I hope to be able to visit biological issues such as these and be able to increase someone’s chances of survival. 

Synthetic Biology and Bad MATLAB

Have you ever worked with a student who just can't seem to write good MATLAB code? Bad MATLAB tends to name variables with uninformative labels, and reuses variables for lots of purpose. It's often called "spaghetti code", because whenever you change one thing in the code, it affects things all over the program. Good MATLAB code only uses variables for a single purpose, so that changes can be made without far-reaching consequences. So what does this have to do with synthetic biology?

Let's think about molecular signals as variables. Nature isn't an engineer, so nature didn't really care to name molecules in any sort of logical manner. Neither 'LasR' nor its amino acid sequence reveals anything about its purpose. But we are engineers, so we ought to do better. If we want to really progress the field of synthetic biology, we should find some way to logically choose signal molecules that indicate their own purpose to the engineer.

More pressing however, is the extensive reuse of signals. Again, nature designs life in a highly iterative process, and doesn't care much to use unique signals. Instead, we should ensure that signals are only used for a single purpose. First, this requires building a family of molecules that doesn't affect nature, yet is completely absent in nature. Second, this requires rigorously adhering to a code of unique signal assignment, so that different groups don't use the same signal molecules.

Like in MATLAB, we can significantly ease the engineering process for biological engineers by separating concerns. Unlike MATLAB, we'll never have debugging tools quite as good as just dropping the semicolon...

One Step at a Time

      Having finished our tech spec review with a pretty successful presentation, our group has decided to move forward with our cancer detection project.  These last few weeks have been largely focused on ways to improve the project and make it more specific.  We started out by identifying several problems we needed to address - we needed to make sure our system could detect cancer "early" (with as few cancerous cells as possible), we had some concerns about immune response to our EBV vector, we needed to pick a final output and we needed to decide whether loss of function in APC was the only marker we wanted to check for.
      In order to make sure our system could detect cancer with as few cells as possible, we realized that we would need some method of amplifying our signal to start producing output.  Luckily this task didn't prove too difficult as Molly was able to find several papers describing a modular signal amplifying system that had been used to produce large amounts of GFP but that we could likely modify to produce whatever we decide to be the output of our system.  With that, the open question remains as to what our output will be.  We think that something as simple as a combination of excreted and membrane-bound fluorescent proteins or luciferases could work but it will depend on where in the lining of the GI tract tumors tend to form (excretions from cells on the inner lining will be much easier to detect than those on the outside); we are still researching this topic.
      Another of our concerns centered around the EBV vector we plan to use.  We were concerned that, especially with much of the population having already been exposed to the virus, there could be a strong enough immune response to destroy our circuit before it ever reaches the target cells.  With a little more research from Katelyn however, we found out that because of modifications to the vector form of this virus, the natural immune response tends to be very low and should not threaten our delivery.  Having bypassed the immune system, our remaining delivery concern was transporting our vector safely through the digestive system.  We believe that we have found a capsule that will remain intact through the digestive system and dissolve afterwards that could house our vector but we are still researching that.
      The final major concern was whether we wanted to focus solely on loss of function in APC.  Natalie provided us with an article that discussed some other common markers of GI cancers that we looked through and considered.  Many of the markers discussed were, like beta-catenin, transcription factors with abnormal activity levels so we thought it wouldn't be too difficult to incorporate them into our existing circuit.  We also realized however that our original circuit had some room for improvement.  The design we presented for tech spec had the possibility of a false negative in the case of a cancerous cell that is constantly being exposed to Wnt - in that case there is no way to tell whether the CTNNB destruction complex is not forming because it shouldn't (Wnt is present) or because it can't (APC is broken).  With some more research we found out that over secretion of Wnt is another common phenotype in cancerous cells so we've decided to focus on improving our original design by accounting for this other possible error in the Wnt signaling pathway.  As of now we're still in the brainstorming phase but I'm pretty excited about some of the ideas we've thrown around.

Success Seems Just Around the Corner

When we chose our project after the three ideas presentation, I knew we were in for a challenge when we decided we were going to try to come up with an early cancer detection method. I was explicitly concerned I wouldn’t be able come up with an creative solution to an issue that billions of dollars of research hadn’t already tried to come up with. While the Wnt signaling pathway is very well studied, perhaps we might have approached it from such an angle that no research group has thought to approach it the same way as us. Even we won’t actually build our system, I wonder if there would be a way to suggest this to a research group to test our system out for us? On the one hand they might appreciate the idea, but on the other they may not want to be doing a bunch of freshman’s projects.

I was overall really happy with the results from the Tech Spec Review. A lot of the feedback was very helpful, but it was almost all stuff we already knew to be thinking about. We were already trying to decide whether this should be an at-home procedure or just something you would do in a doctor’s office, and whether or not our viral vector would encounter an immune response from the body that would nullify our treatment. While the Three Ideas presentation essentially let us know we had a lot of work to do if we wanted to get anywhere with any of our projects, the Tech Spec let us know we were doing well, we just had to keep at it.

The largest issue we had been encountering was the issue of the false negative we were getting. When we realized we had left room for a false negative, it gave me a small feeling of panic. If we weren’t able to resolve our issue, we would have to back track immensely and re-do a lot of our work. However, I continuously underestimate our ability to come up with creative solutions to problems as a group. As individuals it would have been hard to solve this, but it took our group maybe 30 minutes tops of staring at the issue to come up with a viable solution. We were able to propose a clever microRNA destruction mechanism for a constitutively promoted output, where the output would only be expressed if Wnt enhanced the constitutive promoter. I was impressed by the ingenuity of our group, and I know we will be able to produce an incredible final project. I look forward to our final project and the other team’s final project.

Which Output Though?!

The wnt pathway is finally coming together (somewhat).  We are beginning to debug our original system in the hopes of finding a more efficient and reliable system.  Finding a way to reduce/eliminate false negatives, exploring proper marking, signaling, and output, as well as simply improving the pathway are our priorities.

I have been focused on the output stage of the wnt pathway, trying to figure out the most plausible output mechanism.  Originally, we went with generic GFP as it seemed to do everything what we wanted, and most importantly was easy to analyze.  The introduction of additional genomic sequences or markers then altered this original idea.

We chose to include topflash in our design, which uses luciferase as an output instead of GFP.  Luciferase has many benefits over GFP, including most importantly, the better ability to be amplified.  One of the problems we have is the fact that if only a few cells are detected, the fluorescent output may be hard to analyze.  Amplifying the output will solve this problem, and using an output that can be easily manipulated such as luciferase is to our benefit.

There is still a lot to do, but what we have accomplished so far is quite astonishing.  I can't wait to see what will be the eventual outcome of our project, and what the next steps will be.

That False Negative Problem

So whenever you test someone for some disease, you can have a negative, positive, false negative, or false positive.  As far as the falses go, a false positive is probably not that bad.  In the case of our system, that would mean that an output was produced when the person does not actually have cancer. After the output was produced, another test would be performed to actually find the cancer with a scope and it would be discovered that there is no cancer.  Although it would cause the patient a lot of unnecessary grief over their diagnosis, a false positive eventually just ends with the patient being relieved.  A false negative, however, is much more frightening.
Recently, our group discovered a really probable false negative that our system could give when interacting with GI cancer.  Since our system only produced output when Beta-catenin was present without Wnt, the cell would be free to have free Beta-catenin and Wnt and not show that it is cancerous.  If the presence of Wnt and free Beta-catenin was just an occasional occurrence in cancer cells and they would produce the output at all other times, this would not be a problem. However, some cancer cells suffer from hyperactive Wnt (too much Wnt).  Therefore, there would be no output would be produced, but the cell would be cancerous.
We are in the amidst of figuring out how to deal with hyperactive Wnt.  Our current solution is to have two systems.  One system is the old system and the other involves miRNA degrading a second output.  We have also looked at possible ways to use Wnt presence as a repressor and promoter for the same output.  This one-system system would create fewer parts for the cell to produce in order for the system to work, but may be less accurate.  This is a dilemma into which we are still looking.
This issue has made me think of the part of the project on which I was just working. I had to find a way to amplify the output.  I think that we are going to use the modular amplifier that I found even though we have to produce a few more parts.  This reminds me of the two-system vs. one-system debate because it forces the engineer to decide between a larger system built with modular parts vs. a simpler system that is tailored specifically to the issue/goal at hand.  Maybe the second way is better, but I am very grateful that papers have been published and the Registry of Biological Parts has been created to help make the whole field more modular and a little easier to grasp by people just learning things like me.

New Chassis

After receiving feedback from the tech spec, the team now has new direction: to find a new and improved chassis that won't die of malnutrition in the ocean waters.

We identified several candidates, but after much deliberation it was decided that cyanobacteria would, after all, probably make a better chassis than Lee would. So we've been looking into several strains that look promising. Exactly which strain will fit our needs best remains to be determined, and further researching that is our next step. After that is decided, it seems like we're just going to transfer the old device-level system onto the new chassis by looking for new parts that are compatible with the new strain of cyanobacteria. I find it pretty amazing that you can just transfer this kind of system, and here again the versatility of bioengineering, at least in theory, strikes me.

I kind of wish we could actually try this in a lab. It would be so cool.

I Love Viruses! (and other things I never thought I'd say)

This past few weeks in 20.020, I've come to a startling realization:

I love viruses!

Note: that should not be read as "I love experiencing viruses." A clear distinction must be made here. Regardless, recently my job in Team Human Health/Cancer/Turtle has been to look into viral vectors and their human implications, and I am finding that I actually really enjoy it. I have been able to research many different kinds of viruses that are widely used in clinical applications and what makes them unique and effective. The virus we decided on is the EBV/PAC viral vector, which has been widely used in medicine and can hold an insane amount of genetic material. It was recently used to construct a human genomic library. In other words, it can pack a lot of information into a small space. Most people have already had EBV, so they are immune to the wild-type virus. This means that clinical trials have been pretty successful and low on side-effects.

Because of the fact that most people have already had EBV, one concern of ours was that the immune system would recognize and target the host virus and destroy it using existing antibodies. However, further research showed that the immune response to the virus is dependent on the presence of helper viruses found in the wild-type infection. Without these viruses (which are not present in the manufactured vector), EBV can successfully inundate its target cell.

The research on viruses is pretty much complete at this point, so I'll be moving on to helping the team with other aspects of the system; but the EBV vector will always have a special place in my heart (another thing I never thought I would say). I'm excited to see what other interesting things come up as we move on with the project!

We're Makin' It

In the past two weeks, I've seen our decomposition project grow from hand-wavey ideas and concepts to something concrete, with detailed parts specifications and a plan of action to bring it all together. It is very exciting, being a part of this process of creation and seeing how your personal contribution plays just as important a role as everyone else's.

I think it's hilarious how, despite our thoroughness in designing the system, we entirely overlooked the method by which the e. coli would receive their sustenance! As it currently stands, our chassis wouldn't have lasted much time at all, when you consider the amount of energy required to pump salt out and build decomposition enzymes, all while being starved in the middle of the salty ocean.

Wednesday's inventor/investor activity was highly illuminating in terms of just how much capitalism gets in the way of advancing the current states of science and medicine. I voluntarily hindered another team's progress just so I can sign an exclusive deal and rake in the dough, and while the stakes were significantly lower in our little social experiment, I can't help but to think how much these things happen in real life, on a large scale.

Post Tech Spec Thoughts

The feedback we received after the tech spec was very useful: to either switch our chassis or our target location, and to simplify our system. Looking back on it, it seems like it should have been obvious that we should use an ocean organism to solve an ocean problem, but I think we were drowning in our many devices to the point where we forgot to even think of what our system would look like as we deployed it. Our E. coli wouldn’t have had a carbon source or even a native salt water survival system and wouldn’t have lasted very long in the sea. Right now, we have agreed to switch to a cyanobacterial chassis but are still deciding what strain to use- a common strain that floats, or a less-well-researched species that can adhere to plastics and other hydrophobic objects.

As for the device list, we are narrowing down our focus from four targets (PET, polyethylene, polystyrene, and phthalates) to just one, polystyrene. (We will add in others later if we have the time.) We’ll also have to remove my favorite part, the OmpW salt pump, as cyanobacteria naturally thrive in the salty ocean water. We are not sure now whether to even include a similar cell death mechanism, because how much damage could these cyanobacteria really do if they got loose?

The cell death question is now one of a large number of open questions on this project, and it’s kind of difficult to know how to proceed in answering them. I’m almost wishing for another Tech Spec—another chance to regroup, reassess, and move us forward in the best direction possible. This project is also making me realize just how challenging the different aspects of an open-ended project are: narrowing down research so the problem does not seem overwhelming, planning out a timeline for discussing certain aspects of the problem, and balancing higher-level thinking with detail specification. They are all super hard! Hopefully by the end of the semester I’ll have gotten at least a little better at these skills, even if we don’t have a design that would really work.

After reviewing our feedback and planning out a new direction of research, our group is going strong.  Go Team 99 Bottles!

Coloring With Cancer

I really enjoy brainstorming. The process of developing ideas under the assumption that everything is perfect and nothing can go wrong is fun. Actually fleshing out an idea is a much harder process involving some serious reality checking, and that is exactly what I discovered this week. Our project is to develop a biological mechanism to tag GI cancer. Ideally this would replace the current, highly-invasive methods implemented in hospitals today. Most widely used are endoscopies, which involve sticking a long tube with a camera down the patient's throat-- a less-than-pleasant sounding procedure. Hopefully our project would allow patients to physically see something in their excrement that would alert them to the presence of cancer cells. 

This sounds like a simple enough concept. I thought so too, until we actually began looking into how cancer environments actually work. Many of the surface proteins that we had intended to tag are found on normal healthy cells, which increases the possibility of a false-positive. In addendum, the high turgidity and low pH of tumor microenvironments make them nearly indelible to drug access. Our method will need to be able to detect cells on a very nominal level, before that microenvironment establishes. However, this creates a problem, as then the surface proteins will be in similar concentrations to the surrounding cells. 

Despite these obstacles, the team managed to conduct some stellar research and find surface tags that are specific to GI cancer cells. We're still settling on which receptor we are going to use, but at least now we have options that can latch onto our target cells. Furthermore, we found a high-capacity adenoviral vector into which we could transform our desired gene sequence. Our plan involves a large amount of recombinant DNA, so the high storage capacity of the virus is a major draw. It also is highly effective at accessing target cells, so breaking into the tumor microenvironment should be much easier. While the term "adenovirus" may raise some red flags, all of the clinical trials involving its use in other cancer studies saw minimal side effects. 

As I said, brainstorming with no consequences is fun, but I am finding that I definitely prefer the actual design process of a real idea. Sure, it's harder and there are plenty of obstacles, but our project is beginning to come to life, and I'm really excited to see what challenges we overcome next and how our design continues to grow from here.

The Devil's in the Details

      The last two weeks (aside from the much need interlude that was spring break) have largely been spent investigating at ever increasing levels of specificity the projects we have chosen.  It's very easy to see why curing cancer is the subject of such a large amount of research; there are seemingly infinite possible mutations that can lead to the disease making it difficult (if not impossible, at least for the moment) for any one detection or treatment method to work on all possible cancerous phenotypes.  As such we've decided to narrow our primary goal to detecting gastrointestinal (GI) cancers, as that is an area of the body that is fairly accessible.  You can ingest a pill, put something in a piece of food or just straight up use a scope to get things into the GI tract; much easier than something like the brain which has that messy blood-brain barrier to contend with.
      Our decision to narrow the scope of our project has made our job of detection (at least a little) easier.  Since GI cancers are in the same areas and involve many of the same kinds of cells, they tend to have more in common than any two generic cancer cells from other forms of cancer, making it easier to avoid false positives on our test.  The job of finding a reliable marker was still in no way trivial.  We investigated a variety of surface proteins that are common on cancer cells but ruled them out because most were also upregulated in several other non-cancerous diseases.  In the end we decided to focus in measuring an activity within the cells that we are screening for cancer.  According to research we found, one of the most common mutations in GI cancers is loss of function in the APC gene.  We'll go into more detail about how we plan to check for that mutation in our tech spec review this week but I'm pretty excited about what we've come up with thus far.  Overall, I think we have a pretty solid system planned for checking for APC mutation and while I hope we can find a more generalized solution (perhaps something involving the common loss of DNA repair mechanisms), things are looking pretty good.

APC, Our Little Friend

When we first sat down and discussed our project ideas, everything seemed like it would be a breeze. We were able to come up with tons of ideas and it seemed like we could solve them all right then and there. And I’m now coming to realize, just like the rest of my group, why cancer sucks.  Since a cancerous cell is essentially a regular cell that divides more than usual, it makes sense detecting the differences between healthy and cancerous cells would be very difficult—the task seemed insurmountable a few days ago. I found it hard to believe that a couple of college freshman were going to be able to produce anything that billions of dollars of research wasn’t able to produce. It seemed like every time we found a potential avenue for detection, we found article saying, “two-billion dollars went into discovering this detection method could never work.” It was pretty discouraging until we stumbled upon a nifty little protein we like to call APC. It seemed like in the sea of proteins in the cytoplasm, this one just might have been overlooked earlier in cancer research. While it’s possible there’s someone out there researching this protein right now, we were at least able to begin to exploit this. APC is the most commonly different protein in colon cancers, and it seems to have a lot of potential for success with this project. I’m looking forward to everything coming together just in time for the tech-spec review. One small matter that could be an issue is that our method relies on the viral delivery of mRNA. This could be a huge bioethical barrier because the FDA would likely not approve the viral infection of humans for the purpose of only checking if someone has cancer or not. If it were a cure to cancer, perhaps the FDA could reconsider. For this project, however, I’m sure it’s fine to ignore the bioethical side of things for now.  

Signalling spectrum regulation?

It's the end of week 8 of 20.020, and we're finally starting to see what our projects will be looking like! The plastics decomposition projects is progressing well: we've found our enzymes and we have a general idea of how we would like to regulate the system. Now we just have to hammer out some details for the Tech Spec. I shudder to think about how much debugging we would have to do if we were building it for real.

In one of the classes, I was thinking about our signal molecules (TetR, AlcR, ...). All the signal molecules we are using are popular, and probably will be used in other projects. What would happen if our project came into contact with another, and they started messing with the internal signaling in each other's cells? Worst case, this could lead to almost completely unregulated behavior, like the complete shutdown of a feedback loop, which could be fatal if in a larger organism. Best case, both projects shut down and disable.

So I started to think about how biological engineers should negotiate to not interfere with each other's signaling. Electrical and mechanical engineers don't really think about this, because things they don't attach generally don't interact. But when they do, really bad things can happen (see: Fukushima, Challenger). Maybe they need to think about it some more.

The people who have most experience with this, however, is radio communications. Companies sign up to use a specific wavelength for each specific application, so no two companies every have interference. Maybe biological engineers can register a certain class of signals just for them. Preferably ones that don't occur in nature, so nature can use its own domain of signals.

However, this scheme disproportionately hurts small laboratories and tinkerers, who can't afford the fees and are therefore blocked from the market. I don't have a solution, but I think this issue will become increasingly important for biological engineering as more and more projects are put out into the world.

So this is why curing cancer is hard...

The idea that we were going to detect and treat cancer sounded difficult. Obviously no one has really "cured" cancer yet. So we should have expected that it would be a difficult task to take on.  First we looked as what makes tumors different from other cells in the body. We filled multiple whiteboards with different parameters that all had one thing in common: they work sometimes, but other times they create false positives or negatives.  Therefore, we had to narrow what type of cancer we were going to examine. We decided to look as GI cancer because we could report a positive result the same way it was reported in the blue baby project.
Then there were just more papers. I actually found looking for markers of GI cancer to be kind of enjoyable this time. Enjoyable is probably the wrong word there, but I think looking through papers is becoming easier.  I also liked how we were all working together and communicating about what markers we were coming across. Sometimes when we work in small groups in iGEM, we were all working on different aspects of the project and it was difficult to bounce ideas off of each other.  Regardless, through this process we have found something that occurs in many GI cancer cells and we now have a system designed that can detect it.
Designing circuits is also becoming more enjoyable. This is probably because I have a better idea of what we are doing.  Now that I have a general idea about the basics, the problem solving is really fun.   Now if I do major in 20 and ever read this blog post again, I will probably be shaking my head at that last sentence because I just have no idea how much I do not know right now. I suppose that it what is exciting though. Doing really anything with cancer is difficult and there is so much I do not know about synthetic biology and there is so much that is not known in general, but there is just that idea of potential cures and treatments and that is what makes it worth it.  On IB English exams at my high school, there were different writing prompts to choose from and my teacher always told us never to choose the prompt you look at and think "oh I can write everything about that quickly and in one paragraph".  Maybe innovation in general is based on the foundation of never choosing that type of "prompt", whether is be in science, english, math, or really any field.

waddap

We're more than halfway through the course and things are getting technical! It's the slightest bit stressful because I worry I haven't found enough parts to actually specify how to build our system, and I surely can't know all the mechanisms and pathways that go into those parts in the timeframe allotted, right? I don't know. Trying to actually put these things together in a cell correctly would be no laughing matter. I suppose that makes the successful transformations that much more rewarding, but I wonder how many failures will proceed that success, or if it'll ever be reached in the first place.

Tangible Progress

After working on this project for a couple of days, I feel like I have a much better grasp of what creating a prototype would actually entail. Breaking down our system into devices, and then parts, has been really helpful in making everything seem more plausible. It seems that if we complete the design and find the appropriate parts, we could just order a batch of products online and make our project a reality! Of course, I realize that things are not that simple: physical models don't always work the way they should in theory. But working with the theory has been really exciting because there are no physical impediments to limit our progress in designing the project. Our design only has to satisfy logic and previous knowledge of biological parts.

Having said that, I have been surprised at our progress. Instead of being steady, it seems to occur in bursts, when someone finds a part we can use. These bursts are then followed by periods of stagnation in which everyone is researching on their laptop. I wonder if this is what bioengineering is actually like.

And of course, I shouldn't neglect to mention that the team theme song, costumes, and bat signal also seem to be under development.

Still Trying to Cure Cancer...

It's still a work in progress.  Nevertheless we're heading down the right path for our Tech Spec Review next week.  We have settle on a more focused project, rather than blindly attempting to cure all forms of cancer.  We decided to attack gastrointestinal cancer, being that the detection method would be much easier than other forms of internal cancer.  The exact signal is unknown at the moment, but it will hopefully turn out to be much easier and less painful than the previous detection method of sticking scope down the patient's throat.

Our method revolves around the wnt pathway.  One main issue with this is attempting to delocalize the signal given off by one cell, to many, to allow for the patient to more easily detect whether or not they have cancer.  In other words, we need to find a method for the signal to be amplified from the original cell.

This is just one of the many problems we must confront when dealing with such a complex biological pathway.  Cancer sucks, and we're attempting to find not a way to fight it, but to recognize it.  This way, it can be more efficiently and accurately treated in the future.  I'm really looking forward towards how this project will turn out next Thursday; as of now it has a lot of promise.  Also, turtles are cool.

Preparing for the Tech Spec

Tuesday: I’m excited that our design for a plastic decomposition system is starting to come together! Breaking down the system into a device diagram and a parts diagram has really helped me to understand the thought process that goes into designing it. I never felt before that I could engineer something that hasn’t been made before, but this way of thinking has given me confidence that I can approach these problems in a systematic way. It is slow going; our group spent a long time coming up with a device diagram only to spend another long time re-doing it, and I suspect the parts diagram will be constructed the same way. We really have our work cut out for us before the tech spec.

Wednesday: We have moved on from the device diagram to the parts diagram, and now this project is starting to seem a little overwhelming. Where do we even start with finding promoters that work, or compounds that will bind to our plastics of interest? It looks like we may have to narrow down our sensing capabilities to just one plastic, and even that is complicated. The chances are next to none that we will find promoters specific to exactly the plastics we are looking for, but our task becomes more complicated with every step we add to the pathway in between. It’s a lot to think about, for sure, but I still think the project is worth taking forward. Even if our final design doesn’t work out, this experience has already been so valuable to me.

Moving forward, it looks like we will have to think more about our chassis and our sensing systems. E.coli can’t survive for very long in salt water, so we may have to switch organisms or focus on landfills instead of oceans. Sensors are difficult, because most plastics are too big to enter a cell, so we would need some sort of signaling pathway to get our promoters going. We’ll definitely need to address these questions before the Tech Spec next Wednesday, because I’m sure it will give us even more to think about!