Project 2.0

So it seems as if the calls with the experts have prompted both groups to readjust their project goals pretty dramatically. If I learned one thing, it's that I prefer talking to people over researching online. The experts were just so informative and helpful in such a short amount of time. I kind of wish we had gotten to talk to experts earlier, so that we could have picked a more appropriate chassis from the start, but I suppose there's value in exploring the waters on your own first and learning from your mistakes.

Looking back, I feel like we were trying to piece together a system that was logically sound but not necessarily the most intuitive. A lot of choices seemed arbitrary and involved compounds that we happened to stumble upon and seemed to work. After running through the design process once and talking to the experts, I'm starting to realize the value of drawing from the experience of others to obtain a better sense of what tools and parts are available and appropriate in the bio engineering world. 

I'm treating this next phase as our project version 2.0. Vibrio seems like a very viable chassis, and I'm ready to see what the cyanobacteria expert suggests. 

On another note, something that really excited me was the fact that the bacterial expert had been contacted by industry to create something very similar to our project. That means that our idea is viable and in demand! This project has me seriously considering pursuing something similar in a lab as a UROP - I think that if I could work on a project like this in a team and have some control in the direction of the project, I would be working on my dream UROP. 

So Much Can Change in 30 Minutes

On Wednesday, we talked to experts on the topics pertaining to our topics. We thought we were pretty well prepared going into the meetings. We had several questions written out for each of the experts and knew how to present our project to them.  We even knew how to pronounce their names (this was a larger problem than we had anticipated though).  We had people ready to take notes and were open to any information we could obtain from these people who know much more about Wnt signaling and viral vectors than we do.  There was one thing we were not completely prepared for:
"Yeah that is not going to work."
Neither of the experts actually said those words.  They were much kinder and more scientific, but that was the takeaway.  We learned from he viral vector expert that our choice of a virus was not ideal.  When we asked him for suggestions for a replacement, we were again reminded on how much we do not know.  We need to know how long our sequence is and what cells and how many cells we need to infect before we can really decide on a vector.  From the Wnt signaling expert, we found out that one of our issues will be that many of the cells that cause GI cancer are stem cells and that intestinal cells have a life span of about 5 days. There are also four main causes of GI cancer and we had not considered two of them.  After the conversations with the experts, we discussed a new system and each have areas to research, so we have not lost hope.  However, I have definitely been reminded of how little I know and how much I just did not consider. Sometimes the enormity of the subject is frustrating because I know that I will probably never fully understand all of it, but I think that is why the impact of a project is so important.  Even though I know that we will never complete this project in a lab, I am still motivated to push forward with my ignorance and try to just learn whatever I can to create a usable system because I want to help people and for there to be a simpler early detection system for cancer.  Science is great and all, but the "why" matters.

Meeting with the Experts

This week was one of my favorite weeks in 20.20 so far! The experts we talked to were so helpful in answering our questions, probably saving us hours and hours of research. Up until this week, I had the vague notion that our system in its current form would not work, but couldn’t really come up with a definite reason other than that it was kind of a mess. (Natalie described it as a dam with a bunch of leaks that we kept trying to plug with our fingers, which I thought was pretty accurate.) While our system now has a less well-defined goal than before the meetings, I believe we are moving in a better direction now. Such is the iterative design process! It is a little frustrating to be possibly taking a large step backwards at this point in the process, but if it will help our design, that’s what we’ll do.

One of the most important points brought up by the experts was the harmful effects of microplastics and plastic additives. Although we knew we would have to worry about the by-products of decomposition, this concern wasn’t as high on the priority list as figuring out how to make our system work in the first place. However, I had no idea of scale of the real problem: the spread of microplastics to nearly every corner of the globe, their tendency to accumulate in the digestive tracts of marine life, and the detrimental effects of plastic additives such as BPA (which can mimic estrogen and disrupt the endocrine system). We may narrow down to a more specific focus, which we knew from the beginning was a possibility—our goal was so ambitious! One interesting idea we are discussing is to engineer some bacteria to live in fish and chow down on the microplastics they eat. It sounds pretty cool and I think we should run with it, but who knows whether it will work. I’m excited to talk to Danny Ducat on Tuesday, and to see what direction our project heads next!

Experts do know best...

This week was both the best and worst in the class.  We received much more information regarding our project--very helpful information that we never thought to research before talking with the two experts.  However, this information maybe wasn't what we wanted to hear (unhappy face).

Dr. Donald Coen first talked to us regarding our choice of viral vector.  He provided useful insight as to why EBV was good to use in theory, but it would be very difficult to introduce into the gut for a variety of issues.  He told us of the possibilities of other vectors (pox viruses for example) that may be worth our time to research.  After talking with Dr. Coen, we all felt as though we were back at square one--at least we had a wealth of new information to combine with our preexisting knowledge to create a perfect design.

Next, Dr. Xi He, an expert in Wnt signalling told us of the four most common mutations in the Wnt pathway that could lead to a cell turning cancerous.  This will be our other focus moving forward: finding out more about the big four mutations, and trying to implement them into our system.

The next few days will be full of us attempting to make last minute adjustments to our system with the suggestions proposed by the two experts.  I am confident we can get everything researched and implemented before the final presentation, and make the best system possible with the information we have thus far.

An Expert's Opinion and a Student's Shock

This week we had the opportunity to speak to two professionals doing work related to our GI Cancer study: Dr. Xi He, an expert on Wnt signaling, and Dr. Donald Coen, a virology department faculty member at Harvard. Both had incredible insight for our project and were able to provide a lot of great feedback for our team.

That said, speaking with them also made me wonder what on Earth we were doing.

Well, that is a bit of an exaggeration, but the point is that I had no idea how much we still had to cover for our project to even be close to a feasible solution. It's one thing to go online and read literature about a biological system, it's another thing entirely to hear from someone who has spent their entire life researching that system. Sure, both posed many questions we were prepared to answer, but many times their feedback led us to more and more that we still had to look into. For example, in my last post, I raved about the EBV virus. From Dr. Coen's input, it turns out that there are many far better options that I have to look into! Similarly, Dr. He outlined four clear cellular malfunctions that can lead to the development of GI cancer, which we had previously not looked into.

By no means is this a negative thing. Seeing how much work is still to be done was certainly shocking, but now we have the opportunity to improve our system significantly thanks to the opinions of the experts. Getting clear feedback was hugely important to making sure we were on the right track, and though we still have a lot to do, I think we are definitely getting there.

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!