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!