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My First Weeks of Summer Research By Matthew Moulton

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My name is Matthew Moulton and I am a rising senior attending The Cooper Union for the Advancement of Science Art. After I graduate I plan to work as a chemical engineer. I applied to the NYU MRSEC REU program to gain experience and to explore a different scientific field. As part of the program, I am working as a research assistant in the Montclare Lab located in New York University Tandon School of Engineering.

This laboratory focuses on protein engineering. Essentially, the researchers create proteins with a desired outcome. For the summer, I am working with the protein Q. Q’s structure is best described as a bundle of coils. Previous research has shown that at high enough concentrations Q forms fibers that cross-link to form a hydrogel. A hydrogel is a network of polymer chains that are hydrophilic. Hydrogels are used for drug delivery and tissue engineering but most hydrogels are made from synthetic polymers. Hydrogels made from proteins like Q are more bio compatible. My job is to determine the range of conditions that this gel can form under.

q Protein

Q Protein

In order to produce Q ,researchers use bacteria as the factories to produce protein. Here are the steps:

  • The first step in this process is transformation. In this step a DNA (also known as plasmid, shown below in red) that encodes the Q protein is inserted into the bacteria host or factory. For our project we use a heat shock protocol. When the bacteria are exposed to high temperatures, their cell walls become permeable, allowing for the plasmid to get into the cell. The bacteria are transferred onto plates with nutrients that contain antibiotics. Normally, antibiotics kill bacteria. The bacteria that we use are resistant to antibiotics because the DNA plasmid contains a gene or set of genes that can breakdown antibiotics. This ensures that only cells containing the DNA grow on the plate.
  • The plates are left to incubate overnight to allow the bacteria to reproduce. The following day colonies, which are small clusters of cells, are chosen and grown in a solution containing antibiotics. This solution, called media, contains the nutrients necessary for bacteria to survive and reproduce.
  • This bacterial solution is used to initiate a larger volume of media and allowed to incubate until there are a sufficient amount of duplicated cells. Afterwards, a chemical, isopropyl β-D-1-thiogalactopyranoside, is added to the mixture to trigger the production of the Q protein. Isopropyl β-D-1-thiogalactopyranoside binds to a repressor protein (in pink below) on the DNA(shown below at the operator) and changes the repressor so it can no longer bind to the DNA. Once it comes off, another protein RNA polymerase (in purple) can take its place and begin interpreting the DNA so it can produce protein.

Gene Repressor

 

While this is just the first step of my experiments, I have learned a lot. I already knew how to perform transformation from a class I took at my university but I never learned how to produce protein. I was surprised at how many steps were involved. Protein production or expression is a process that takes several hours because once isopropyl β-D-1-thiogalactopyranoside is added to the solution, one has to wait for three hours for the cells to multiply.

colony

For me, the most difficult part of protein expression was picking colonies. To pick a colony, a pipette tip is used to gently scrape a colony from the plate and place it in a tube. The first time I tried to pick a colony, I had trouble finding one because the colonies were so small so I accidentally poked through the plate!

I am still new and I make mistakes but I look forward to learning more about protein engineering. Do you have any advice to share as I learn more about protein engineers?

Let’s chat on Twitter:@matthewantonym
Matthew Anthony Moulton

The rationale behind the dual MD/PhD degree By Andrew Wang

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(Image source)

One of the first questions I get asked by many people when I tell them that I am an MD/PhD candidate is “Why?” Usually I reply with some flippant answer about stacking degrees next to my name or avoiding a job, which gets some chuckles. However, for anyone considering whether to pursue the degree, this is just part of the story.

Many authors more eloquent than me have written about the increasing need for physician-scientists. The National Institutes of Health (NIH) has put together a helpful graphic showing the pathway of a physician-scientist, whether through a dual MD/PhD degree or a solo MD. While you do not necessarily need a PhD degree in order to conduct research as a physician, you do need an MD to see patients, and the dual degree offers a number of benefits beyond either individual degree. For me the MD/PhD degree is a marriage of the humanistic and technical parts of medicine and allows me to help patients both in the future and in the present. I’m hoping it will allow me to explore topics at the intersection of medicine and technology where historically there has been a disconnect in expertise.

The sheer complexity of the human body, and its variability between individuals, makes a medical and clinical perspective very useful when designing new therapies or diagnostics. In my field of biomedical engineering, in tackling these challenges it is often easy to reduce patients to “subjects” or “users”. We are sometimes guilty of fitting a patient to a solution rather than fitting a solution to a patient. And even when a solution is designed for a problem, oftentimes there are practical and logistical considerations that prevent the solution from being usable. This is mostly just the nature of biomedical research, and not necessarily a bad thing. As an aspiring physician-scientist my goal is to keep my research grounded, and at the same time derive inspiration for it from my interactions with patients, each of whom has their individual needs and desires.

In addition, physicians have also increasingly taken on a role as educators of technology. We are asked to provide advice on everything from vaccines, a topic which we are intimately familiar with, to robotic surgery, a topic which we are perhaps less familiar with. It doesn’t help that there is a whirlwind of information, and sometimes misinformation, available online and through various media that can cloud public perception and lead to patients ignoring or distrusting the advice of their doctors.

To be sufficiently prepared to explain recommendations to patients and advise scientists alike, physicians should be intimately familiar with reading and evaluating peer-reviewed research, including basic science and translational research. For example, recently I saw a headline on social media about scientists keeping brains alive after death, and the ensuing predictable comments about Frankenstein. Physicians are tasked with seeing past the media advertisement, understanding more precisely what exactly is being done, and explaining such to interested parties. This is an often overlooked benefit of PhD training that extends beyond a specific field.

One of the biggest concerns for many people is the length, or perceived length of the program. Because an MD/PhD degree involves two complete degrees, the length of study is usually around 8 years. As I wrap up my first year however, I have to say that the time goes by extremely quickly as you study and conduct research. In addition, most combined degree programs offer some level of tuition support, often a full tuition waiver for medical school as well as a graduate stipend for the duration of your enrollment. These factors allow you to graduate medical school without needing to repay debts, and are also enough to support a modest lifestyle. If you are passionate about biomedical research and are interested in exploring your options feel free to reach out to me or another current or former student. I’m looking forward to the journey ahead.

Andrew Wang
I meant it when I encouraged you to reach out to me! Find me on Twitter at @acuteWangle

My Unexpected Venture into Science by Julia Monkovic

My Unexpected Venture into Science
By: Julia Monkovic

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Every time I visited my grandparents’ house as a kid, I was always a little scared to go into my grandpa’s office because of a giant picture of what I thought was a bug hanging on the wall. Closely followed by my dad, I grew up thinking my grandpa was the smartest person in the world. What I didn’t know about them was their common passion for STEM – both of them are chemists. Years later, this childhood vision still holds true. As it turns out, that big picture of a bug is actually the structure of an organic molecule my grandpa synthesized that’s now being used as a nausea treatment for chemotherapy patients. Starting with him and passing through my dad, science has crawled through my family and somehow made its way to me – something I never would’ve guessed just a couple of years ago.

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Despite the amount of science present in my family, as I grew older I became more and more resistant toward the field. In high school, my interests circled around reading and playing the flute – I didn’t enjoy the science classes I took, finding them boring, intimidating, and not for me. So in my senior year of high school when it came time to deciding what to study in college, my friends were so shocked I chose to go into engineering they thought I was pranking them. I laughed along with them, while at the same time being driven by fear, the unknown, and a spark of passion to create change.

That spark started not by any positive inspiration or revelation, but through a moment of frustration and despair as I watched a seemingly incurable disease take over my brother’s life. One evening while my family had another argument over which medicine or doctor to try next, I wanted to take matters into my own hands and went to Google to search for other forms of treatment available to my brother. Despite the great successes and advances in the medical field of recent decades, through this experience I felt incredibly frustrated with it at the same time. Many confusing articles later, I stumbled across biomedical engineering. At that time my feelings of anger and defeat turned into ones of pressing eagerness, as I began to believe that pursuing this field was how I could make a change in the lives of my brother and those like him.

Through this experience science began to mean more to me than just a sector of subjects in school. Rather, it’s a way of thinking that we have the potential to help heal and improve the lives of people around the world. It can give us optimism and hope in times of despair and allow us to come together to work collaboratively towards our goals, as science is a team sport rather than an individual one. Science isn’t about memorizing formulas or reaction mechanisms: it’s about asking your own questions, developing your own theories, and eventually finding your own answers to the unknown. Growing up I always felt like science “wasn’t for me,” but over time I’ve realized that science encompasses everything we do, and therefore it’s naturally a part of me.

This transition into STEM was anything but easy. Because of my lack of a science background I was worried people wouldn’t take me seriously. I was hesitant to ask questions in class for fear of sounding stupid and still struggle a lot with confidence. I gain inspiration and confidence to persist through the encouragement of my family and friends, along with the great opportunity to work in a lab that designs ways to help fight diseases like my brother’s.

As I said earlier, science is not something that can be done alone: I’m thankful for my dad and granddad for giving me a platform to grow from, and for my mentors and professors for taking a chance on me and seeing the potential in me before I saw it in myself. I now know that in order to go into the sciences, you don’t have to be the “smartest person in the world.” All it takes is a strong support group and that one spark of ambition to create change.

-Julia Monkovic
@JMonkovic

Succeeding at Failing By Michael Meleties

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Succeeding at Failing
By Michael Meleties

I’ve never had a failed experiment; is that because I’m the smartest person who’s never made a wrong move and deserves all the awards?

I’d love to believe that, but I think it actually comes down to how you respond to perceived failures. Failed experiments can be defined as experiments that do not meet the proposed objective. I’d postulate that the broader objective of each experiment is to continue gaining knowledge, so as long as something has been learned, the experiment is by definition a success.

This even holds true in something as mundane as setting up a dialysis bag. Dialysis is used to separate molecules in solution, using a membrane which is clipped at both ends, forming the dialysis bag. I’ve dropped dialysis bags (they’re slippery!) and even lost samples multiple times in my work. While I was frustrated with myself for not being able to accomplish something so simple and thought I was failing at doing this, what I eventually realized is that with each “failed” attempt I was actually learning what works for me in setting up dialysis. It started with setting up a boat to catch any dropped sample, and towards the latter stages I felt out more efficient ways of holding the bag to prevent slippage. Over time my entire set-up was optimized so that everything was where it needed to be when I made dialysis bags.

Dialysis is a small task that is common in protein engineering labs, so how does that make me a successful researcher? It doesn’t. The success is found in continuously learning from each attempt. I can think of countless experiments that haven’t gone the way I wanted them to when I first did them. However, I can’t think of any that I didn’t learn from.

I believe that this persistence and resilience is one of the cornerstones of research. If there’s one takeaway from this posting, I’d want the reader to re-evaluate their perceived failures and see them for what they really are: minor successes leading up to the big one!

Michael Meleties

I’m curious, what are some of your successes? Tweet me at @m_meleties

The GRC Magic by Priya Katyal

The GRC Magic

Recently, I had the privilege to attend the Gordon Research Conference (GRC) at Waterville Valley, NH. For those who are unfamiliar with GRCs, GRC is considered very prestigious with admissions contingent upon acceptance of an application. These meetings are typically attended by world renowned experts from leading institutions and industries. The conference has a ‘unique format’ where you can interact freely with the experts.

When I came across the GRC on Preclinical Form and Formulation for Drug Discovery in late March, I realized that I had missed the deadline to submit the abstract for an oral presentation. Fortunately, the poster abstract submissions were still open. In filling out the application form, one has to justify conference attendance and contribution to the meeting. My advisor mentioned that many people apply to these conferences but not all are accepted and asked me to come up with a thoughtful answer. I still remember I struggled in formulating the best answer, with my inner critic dragging me down at each response. I was turning down my own application as I was afraid of not getting selected. After wrestling with my thoughts, I finally put together my reasons for attending the conference. However, I was still not satisfied; I had become a prisoner of my own mind, striving for perfection. After receiving feedback and reassurance from my mentor, I was finally set free from my own self-doubt. Besides discussing the aspects of my work and its impact on human health, I also included how attending GRC would expand and improve my future experimental/scientific approaches, and most importantly the value of gaining feedback from experts in the field that together make such work possible. I finalized everything and submitted the application.

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Surprisingly, the next morning I received an email saying “Congratulations! You have been accepted to attend the GRC”. I was happy to secure the invitation and elated to attend the GRC.

When I attended the conference, I was pleased to receive positive feedback on my poster, but I never thought that I could make it all the way to the ‘Top 25 Posters’ and then further to ‘The Best Four’. This honor meant more to me than my other poster awards, considering that I was selected by a jury of my peers.

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Winning this award has confirmed that the work we have been doing is worth the effort. I want to send a big shout out to the members of Montclare lab/Liu lab, and of course, thanks to the conference organizers/attendees who voted for me. It was my first time attending the GRC and it was definitely one to remember.

The experience at GRC has made me realize that doubting your abilities is normal (we all do), but I shouldn’t let that stop me from pursuing my dreams. I have long considered the GRC to be my dream conference, one that is attended only by the elite of the elite. I feel everyone should believe in the magic of their dreams, and don’t be afraid to push yourself. And if you are, don’t be afraid to seek advice. The results might amaze you, too!

-Priya Katyal
(@pkatyal18)