Crossing the Grad School Bridge of Self and Scientific Discovery

Since 2010, the CIRM Bridges Program has provided paid stem cell research internships to students at California colleges and universities that don’t have major stem cell research programs. In order to keep in touch with these interns, The Stem Cellar has an ongoing CIRM Scholars blog series, inviting alumni from our training programs to reflect on the importance of their internships, to update readers on their career path and to give career advice to the current interns.

The blog below, written by Mimi Krutein from the 2011 Bridges program at Cal State University San Marcos, is based on a presentation she gave in late July at the 2017 Annual CIRM Bridges Trainee Meeting in San Diego. 

Mimi Krutein

The science graduate school experience is not at all what I was expecting. I imagined it as a mentally stimulating flurry of discoveries and training; before I started I pictured a cross between Harry Potter and The Magic School Bus.  What I got, and what most graduate students get, is a vaguely escorted slog into a land of uncertainty and imposter syndrome, sprinkled with fleeting moments of clarity and excitement.  But don’t get me wrong; it is worth it.

My personal road to graduate school was quite unorthodox.  I entered California State University San Marcos (CSUSM) as a nursing major, because I had a genuine interest in medicine and was fascinated by the complexity of the human body.

 It also didn’t require calculus level math, so I was sold.
I generally enjoyed my courses but everything changed for me when I took microbiology.  It was my first introduction to basic science.  Disease mechanisms of microorganisms blew my mind, sparked my curiosity, and catalyzed a shift in focus that never readjusted.

It was then I decided to add a biology minor to feed the beast, but didn’t have the confidence to switch majors completely.  The pre-nursing program actually advised me not to add the minor; my grades at that point were good but not stellar, and they thought that the new load would be too difficult.  That summer I formally applied to the CSUSM nursing program and was rejected, missing the cutoff by one point.  Chalking it up to fate, I turned gracefully on my heels and belly flopped into a molecular biology major with open arms, calculus and all.

A few semesters passed and I desperately craved more lab time so I applied to 12 summer undergraduate research programs and was swiftly rejected due to lack of experience.  The only position I was offered was a 100-hour, unpaid internship at a tiny biotech composed of 5 people, where we utilized bioluminescent phytoplankton to monitor water toxicity.  Then I joined the only research lab at CSUSM with an opening, and under Dr. Betsy Read I studied the metabolic pathways of the model organism Emiliania huxleyi, also a phytoplankton.

As much as I loved the lab and industry training I was receiving, I wanted to integrate my fascination of human medicine with my passion for laboratory science.  Betsy pulled me into her office one day and asked the very obtuse question “what do you want to do in science?”  To her surprise –and slight disappointment I’m sure- I told her that I didn’t want to stay in phytoplankton, but rather explore medically relevant research, and study human disease.  Happily she lit up and frantically told me about the CIRM Bridges internship that would be perfect, the caveat being that applications were due that very day.  I received a 24-hour extension, and was later accepted for the 2011 program.

I was equal parts inspired and terrified
For my CIRM internship I joined Tobin Dickerson’s lab in the department of chemistry at The Scripps Research Institute.  I received excellent one-on-one training in a small lab studying highly infectious agents, primarily botulinum toxin.  Now, botulinum toxin has an extremely simple mechanism of action, however, it is also the most potent neurotoxin known to man.  Approximately 1 gram of aerosolized toxin can kill 1 million people; and the bacteria that produces it, Clostridium botulinum, is relatively easy to propagate, making it a potential bioterrorist agent.

iPSC-derived motor neurons. Image courtesey of Mimi Kreitin/The Scripps Research Institute

For this reason, The Department of Defense gave us a grant to pursue high-throughput screening of small molecule inhibitors that could block the effects of this toxin.  I assisted in the screening and follow up tests on individual inhibitors.  At the same time, I established a robust method for generating motor neurons from human embryonic and induced pluripotent stem cells.  This work provided us with a virtually endless pool of boltulinum-sensitive cells for the use of cellular studies with prospective inhibitors found in our initial screens.  Deriving the neurons from stem cells also eliminated the need for expensive and tiresome motor neuron harvests from animals.  The cells I produced in the lab presented as bonafide motor neurons because they produced an appropriate dose response to live toxin.

I finally felt like a real scientist
After my internship, I was formally hired by the lab as a part time technician while I finished my last year of classes as CSUSM.  My two years of work in the lab resulted in three publications, one of which was accepted for the cover of ACS Combinatorial Science.  More importantly though, the years I spent in the Dickerson lab provided room for me to grow into myself as a scientist, receive unparalleled training, and gain perspective on what it meant to be in the thick of academic research.

After many discussions with my peers and mentors, I decided graduate school, ideally a PhD track, was the next step for my scientific career.  I knew I loved research, but I wanted to learn how to think, how to approach unanswered questions in a productive manner.  I wanted to be trained by everyone who could provide me with knowledge.

I was just plain hungry.
And like most 20-somethings on the edge of graduation, my passion was mixed in equal parts with indecisiveness.  I really didn’t know what I wanted to study, but I knew I wanted to utilize my stem cell training, and I knew what made my mind light up; I was -and still am- fascinated by how diseases work on a cellular and molecular level.  So, after months of searching, digging, and crosschecking, I applied to a dozen translational research programs across the US.

And then the news arrived
While running late to a class, I got the acceptance email from my dream school; the University of Washington. After reading the subject line I was frozen with disbelief, I called my mom, forgot where I was going and took a stroll the other direction until I realized I had a test waiting for me.  It never occurred to me that I could actually do this for real.

My first day of grad school was one I will never forget.  After a lukewarm five minutes of awkwardly chatting with my new postdoc lab members, we go out to get coffee and I proceed to faceplant in the middle of a puddle-filled crosswalk directly in front of a truck.  I skinned my knee and sliced my hand open, but magically managed to keep my coffee upright.  Understandably, my newly acquired lab members didn’t let me touch anything of real importance for 2 weeks.  Even after being considered a ‘seasoned’ graduate student I still knock over racks of pipette tips or spill liters of E. coli cultures on my new jeans.  Such is the grad school life.  Part of me hopes once I earn those fancy three letters after my name, I’ll evolve to the perfect scientist, but I won’t bet on it.

To those of you considering graduate school
I’ll end with these parting thoughts. Obviously, I’m still not on the other end of this whole grad school thing, but I can tell you from the four years I’ve spent doing this so far, there has been no experience more rewarding and humbling than pursuing a PhD.  If you find yourself interested in taking the leap in a similar direction, know that if you choose this path, it’s a marathon, not a sprint so take care of yourself through the process.  Maintain a strong support system, both for your personal and professional well-being.  Foster relationships with your peers to gain strength in numbers and build mentorships with individuals you admire to perpetuate curiosity.  Choose your home lab thoughtfully; the Principal Investigator to Student dynamic is the cornerstone of the graduate school experience; you can’t be on different pages with the lab’s leader and expect to write the same story.

Imposter syndrome is the greatest barrier to your success
I spent 22 years wholeheartedly believing I couldn’t do the thing I’m currently doing, and I’ll tell you guys a secret, some days I still feel that way. But it’s vital to recognize that you are worthy of success and not defined by your failures.  Lastly, find humor where you can and stay hungry for opportunities that you believe are just outside of your reach. And stay hungry for knowledge, it’s one of few things that doesn’t expire.

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