Summer Entrepreneurial Experiences

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Week 8: How it Went

Monday, July 15, 2013 2:37 pm

Even though there is plenty of time left in the summer, my research is almost at its end. I leave in a few days for a long family vacation (this is why I started so early in May) and will return for one more week at the beginning of August. Unfortunately, we have not yet been able to develop a gel electrophoresis method for differentiation between “plain” and DNA-functionalized nanobeads. We have, however, developed several electrophoresis methods that cannot do this. The elimination of possibilities isn’t the worst thing in the world; of course I would have preferred to immediately figure this out, but that’s generally not how things work.

The best part of this summer (and the only concrete success, honestly) was the successful development of a new polymerase chain reaction protocol for the intentional and predictable production of DNA fragments of particular sizes. This made the rest of the project easier because initially we were struggling to use an already-established PCR procedure.The most exciting moment in this process was turning on the UV source (the DNA dye we use is only visible under UV) to find that our fragments were perfectly sized.

The worst part of the process was really just that we weren’t able to make any considerable progress on the main goal. It seemed like we had a lot of good ideas that in theory could have worked but in practice did not do so well. However, failure in research is to be expected. I wrote in my first blog post that I expected a lot of trial and error and mistakes, and I definitely encountered both.

My hope is that I can continue to work in Dr. Guthold’s lab over the school year, either on this project or something else.

Week 7: Leadership and Management

Monday, July 8, 2013 2:03 pm

From my experiences in the fluidly-structured environment of the entrepreneurial venture that is NanoMedica, it seems like leadership often comes from within the group rather than from a particular person. As I’ve mentioned before, good ideas are probably the most important and necessary guiding step in the development of a new scientific technique. These can come from any person involved; the more experienced collaborators do an excellent job of listening to and valuing the input of all others. In a group of self-motivated people, blatant directions aren’t entirely necessary–loose guidance toward a general goal will almost always suffice. (The only time that true ‘leaders’ or ‘managers’ emerge is when decisions must be made regarding finances.)

As far as my personal entrepreneurship is concerned (and as I have mentioned before), I’ve certainly been surprised and perhaps even overwhelmed by the amount of freedom I’ve been given in my subproject as I work closely with only Victor. Perhaps I feel this way only because our success has been limited, but right now I don’t know how well suited I am to a very open-ended area of research (which honestly is probably all research). At this point in my scientific education, with my limited knowledge, I would probably appreciate some more concrete directions. Maybe this is because I could then arrogantly place the blame of failed ideas on someone else (kidding!), but failed ideas are an integral part of the process.

Week 6: Challenges and Competition

Monday, July 1, 2013 7:43 pm

Like virtually any start-up company, money is probably the most significant challenge facing NanoMedica. It limits the company on two fronts: 1. ability to pay employees/maintain lab space and 2. cost of lab equipment and materials (which can be shockingly expensive). These issues are being handled in large part by grants from groups such as the NIH and NSF and by partnerships with various departments of WFU, as well as the new Wake Forest Biotech Place.

Another challenge facing NanoMedica is the inherent unpredictability of developing an entirely new scientific technique. It is impossible to know when exactly the drug discovery method will be ready for use and income production. Until this happens, NanoMedica intends to make some money by offering more standard DNA sequencing.

As such a small company, NanoMedica’s main competitors in the fields of both drug discovery and DNA sequencing are firmly established, large-scale companies that have seemingly endless resources of both human and financial variety. In the field of sequencing, NanoMedica is competing against companies like GENEWIZ and the Beijing Genomics Institute; in drug discovery, they are competing against massive pharmaceutical companies that have the resources to continue using less efficient, more traditional methods of analyzing target molecules.

NanoMedica’s advantage in this competition is that their small numbers of employees and customers would allow for more open lanes of communication and faster turnover of services. This bettered customer service would likely result in an increased price, but many companies would probably find the trade-off to be one worth making.

Week 5: Company Culture

Monday, June 24, 2013 2:11 pm

NanoMedica is extremely relaxed and laid-back, but also seems to be quite efficient. Everyone is encouraged to voice their opinion(s) and show their most recent results at the weekly meetings and bigger decisions are usually made by the more knowledgeable/experienced collaborators debating and reaching a consensus. For my subproject that isn’t directly related, I’ve been amazed at the amount of experimental freedom I’ve been allowed. Sometimes I find myself wishing I had more concrete instructions, but I know that making my own decisions makes this a more worthwhile (and entrepreneurial!) experience.

Because much of the work being done is not well-understood, failure is almost expected, and accordingly success is celebrated very enthusiastically. I would describe it as an approach of encouragement in the face of failure and reinforcement in times of success (so basically encouragement all the time). When something does seem to fail, people are always full of ideas that could help to resolve any underlying issues. The same is true to a lesser degree for success; while it is almost always possible to make improvements in experimental design, deviating too far from an already-tested path probably isn’t wise.

Most actual labwork is done independently, but the protocol design is often done in groups or at the least discussed between people doing similar experiments. This works well because it ensures that multiple sets of eyes are present to spot potential errors. Often, several people will act as an assembly line of sorts–each carries out a procedure before passing the product to another person to be tested in a different way.

This culture of open discussion ensures that all ideas are heard and that the best ones are recognized and generally put to use.

Week 4: Progress

Monday, June 17, 2013 1:53 pm

We’re really just now getting to the primary focus of the project; we had to deal with a lot of preparatory obstacles that weren’t expected. The most time-consuming of these was probably the complete overhaul of our polymerase chain reaction (PCR) protocol so that it allowed us to produce DNA fragments of several different sizes. This mainly involved designing new primers (DNA sequences that function to limit the size of a produced fragment); this was a process I was only vaguely familiar with. After researching and finding several sets of guidelines, Victor and I spent 2 or 3 full days scrolling through 48000 base pairs, searching for desirable primers. Hoping we didn’t waste any money, we ordered the primers and used them for PCR. Kind of surprisingly, it worked perfectly on our first attempt! We now have four different lengths of DNA that we can attach to nanobeads.

What has surprised me most is probably the legitimate interest in our project by virtually everyone involved with NanoMedica. It impresses me that NanoMedica is concerned not only about their business plan, but also about scientific progress.

I’ve pretty much learned what I expected to–a lot of biophysical research techniques and that a lot of things can always go wrong in research. Things not working as expected isn’t always a bad thing, though, as it can reveal better alternatives.

At the very least I think we can replicate the results of a few papers available on the topic of DNA-nanoparticle attachment, but our own publication is of course the ultimate goal.

Week 3: Obstacles

Monday, June 10, 2013 2:13 pm

NanoMedica was most likely the brainchild of Roger/people involved earlier in the process who I haven’t met. The founders of the company acknowledged that cost, labor, and time were the three limiting factors that made drug discovery such a difficult process. To attack these problems, they wanted to assemble an interdisciplinary team made up of physicists, engineers, chemists, and biologists to attack the problem from multiple points of view. The ultimate goal was the development of cost-, labor-, and time-efficient methods that still had a high likelihood of finding new drug molecules.

Like any other start-up, NanoMedica hit lots of bumps in the road. These bumps included the high start-up costs of a scientific company with little revenue-production power and accordingly the difficulty of obtaining/renting lab space without great financial stability. These problems were remedied by the recruitment of stakeholders/investors; I figure that Roger’s ambition convinced them that this idea would become a reality. Additionally, as of very recently, NanoMedica has reached an agreement with WFU Baptist Medical Center to obtain a lab space in Wake Forest Biotech Place. While I haven’t seen this building myself, I have been told many times that it is a beautiful space. It seems like everyone involved is extremely excited.

Perhaps the biggest hurdle NanoMedica overcame was the overhauling of their main development when they realized that a better alternative was available. More specifically, they switched from a technique called atomic force microscopy to the use of next-generation DNA sequencing machines because they would be faster and less prone to error. I can only assume it was difficult to decide that several years of work should be set aside in favor of something else.

Of course, there are lots of mini-hurdles each and every day as a part of the nature of research. There is a lot of trial and error, and it’s always possible to mess something up even when you know exactly what the procedure should be (I did this just a few days ago). These obstacles can be overcome simply with caution and attention to detail.

Stephen

Week 2: The People

Monday, June 3, 2013 12:12 am

As I mentioned last week, I’m working under a company called NanoMedica; it seeks to use nanotechnology for medical applications, like drug discovery. Following the suggested posts, I thought I would write a little bit about the people I’ve been working with.

Dr. Roger Cubicciotti is the founder and CEO of NanoMedica. I know he has a history of involvement with biotechnology and has even invented his own fluorescent dyes. He is extremely ambitious and knowledgeable, but also very approachable, which makes him a pleasure to work with.

Dr. Martin Guthold is a professor in the WFU physics department and (I think) Chief Scientific Officer of NanoMedica. Having had him for both of my introductory physics courses, I can say that he is an excellent lecturer/teacher and a very kind person who does all that he can to help his students. His willingness to involve undergraduates in research is a big part of the reason that I received this fellowship. Drs. Bonin and Macosko of the physics department are also associated with the company. I don’t know either of them particularly well, but, from what I’ve seen, they are also very willing to involve undergraduates and open to helping students.

Jason Gagliano is (I believe) a scientist for NanoMedica, a research associate in the physics department, and a part-time Ph.D. student in the biology department. He has a vast knowledge of laboratory methods and is always open to my questions. Kara Libby is another employee of NanoMedica. She has worked in a variety of lab situations and accordingly also has a wealth of knowledge. She, too, is always willing to help.

Victor Yu is in theory my “partner” on my project but in practice much more like a teacher or a mentor. He just graduated from WFU with a degree in biophysics. He has been a member of Dr. Guthold’s lab for a couple of years now. I’m fairly sure he received an entrepreneurial summer fellowship and is now an employee of NanoMedica–this shows how useful these can be! Victor has spent the last couple of weeks with me following him around like a sheep, watching his every move. As of the past few days I’ve been a little more independent, but I will probably always be asking him for advice and ideas.

As I kind of touched on last week, my project is used kind of as an analysis technique for the preparatory phases (bead-DNA attachment) of the main drug discovery project. It fits in with the overall mission in that it involves learning more about nanotechnology and trying to make it applicable and useful to medicine.

The physics department/NanoMedica has been a really enjoyable place to work so far. Everyone seems to be doing their own thing, but they’re all willing to help others and to explain what they’re doing. I think this is an environment where I can learn a great deal about biophysical research in a short span of time.

Biophysics Research: A not-so-Straightforward Process

Thursday, May 23, 2013 9:43 pm

Just a brief introduction: My name is Stephen Eason, and I’m a rising junior. I’m a biology major (with intent to declare minors in chemistry and physics), and ultimately I would like to go to medical school.

My internship is under NanoMedica, LLC, a local start-up company founded by Roger Cubicciotti, Ph.D. that seeks to use nanotechnology to make easier the process of drug discovery. NanoMedica is partnered with Dr. Martin Guthold and several other members of the Wake Forest Physics Department. Because he has been my professor for two semesters and was the main catalyst in my receiving of a Summer Entrepreneurial Fellowship, Dr. Guthold will probably be my main adviser over the summer.

To avoid a lot of unnecessary detail, my primary responsibility will likely be to perform lots and lots of gel electrophoresis (the separation of particles by size and charge via application of electric current through a porous matrix) of nanobeads with DNA attached to them. The goal of this process is to hopefully determine methods of characterizing and describing the quality of bead-DNA attachment as a function of variables like bead size, DNA quantity, and environmental pH. These methods of characterization could be useful to the company, as bead-DNA attachment is an important component of the drug discovery method. (I have already been here for about a week–so far I’ve learned several procedures that will be necessary over the course of the summer and produced some results.)

Dr. Guthold thinks we (I am working with/under a recent WFU graduate named Victor) can obtain enough data over the course of the summer to write a paper for potential publication, particularly because Victor has some previous data on the subject. I don’t know that I really expect to write this paper by the end of the summer, but it’s certainly a wonderful prospect to have in mind.

I expect to learn that scientific research is not a straightforward process. I expect that there will be lots of trial and error, mistakes, and tedious procedures. However, all of these various difficulties will help me in the expansion of my critical thinking and problem solving abilities that are so instrumental in science.

I hope everything is going well for everyone else.

Stephen

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