Random thoughts on failure
Two of my grant applications were rejected recently, and I just wanted to share some of the stuff going through my mind.
Rejection sucks, but it doesn’t make my research less important and it doesn’t mean I’m not good at what I do. I will acknowledge that I’m lucky in that I already have funding for my research, so these rejections aren’t real barriers for my project. A few years ago, I applied for 4 predoctoral fellowships at the same time (October-December 2016): the Ford foundation, the Soros foundation, the Nation Science foundation, and the American Foundation for Pharmaceutical Education (AFPE). I was rejected from Ford, Soros, and NSF, early into 2017, and still had to assist my PI’s* R01 diversity supplement. Those rejections hit me hard, and in the first submission, the supplement wasn’t funded. The AFPE fellowship was awarded to me in March/April 2017, in the middle of rewriting for the second submission of the supplement. It helped morale and removed some of the pressure I was facing, but regardless, I knew I couldn’t give up. My PI* ultimately did receive a supplement to his R01 to support my research, which is meant to serve as support me so that I can apply for independent funding: an F31.
My F31 was not discussed, meaning just that its not in the top 50% of applications received by the NIH at the same time. I’m waiting for the summary statement, which will tell me what reviewers’ thought strengths and weaknesses in my application were. Some things, I can’t change, like my undergraduate experiences; other things I’m actively working towards, like publishing my first 1st author paper.
Publishing a research paper is a requirement of every academic, and it shows in the adage: Publish or Perish. Research papers “show” productivity and success, although like every metric, there are ways to game things, and you should always think critically about what things really mean: how difficult was this to accomplish? How new are the findings? How does this fit into the broader scope of science? Science is hard enough, and constantly feeling the pressure to publish and get grants is draining. Ironically, its hard to get one without the other, kind of like an entry level job asking for 4+ years of experience.
Why haven’t I published?
Science isn’t linear, its just presented that way, and the more original your ideas are, the harder they are to take off the ground. I started my project somewhat related to our lab’s expertise: P2X4 receptors. Previous studies showed that they somehow regulate alcohol consumption in mice, since deleting the P2X4 receptor gene increases alcohol intake, and potentiating the receptor using a drug called ivermectin reduce alcohol intake. How/why this occurs, we don’t know.
Another kind of receptor found in the brain, NMDA receptors, are very important in memory and learning. NMDA receptors are more well studied and understood than P2X4 receptors, but harder to drug. My hypothesis was that these two receptors interact, and alcohol, which affects both receptors, dysregulates the interaction, and contributes to addiction.
Getting the project started meant learning new techniques, like oocyte (frog egg) electrophysiology and microinjection. I also had to purify DNA and make RNA by myself, which took a while to learn, since we didn’t have a dedicated molecular biologist, and we didn’t have anyone in our lab who knew much about NMDA receptors. Our collaborator at the Medical University of South Carolina helped me tremendously in a few ways: 1) he sent me DNA for various receptor types 2) his papers were very well written, so I was able to replicate a lot of his experiments easily 3) he answered any questions I had through email. Nowadays, the experiments are well designed and fairly straightforward, but in the beginning, we had to play around with a lot of different variables, like the buffers we used, the amount of RNA we injected, how much to activate the receptors, etc.
Things were going relatively smoothly, until the summer of 2018, when I had to spend 10 weeks at the University of Illinois, Chicago, to learn brain slice electrophysiology. By spending the summer in Chicago, I had to pause my project, and upon returning, I had to setup the brain slice technique in our lab. The experience was worth it, because I learned some really cool techniques that will let me take my project to the next level.
Distractions can be good
I’m weird in that I like learning about EVERYTHING, not just what is directly related to my PhD project. I completed a Masters degree in the Management of Drug Development (MDD) last semester and I’m taking classes in the Marshall School of Business to learn more about what Pharmaceutical companies look for in new ventures. That’s an invaluable piece of taking science out of the lab and into clinics. This is often referred to as the “valley of death”, something I’m actively trying to avoid with my work.
Some side projects I have in lab are programming a robotic screening system, called the Roboocyte 2. The Roboocyte 2 can screen drugs/compounds non-stop, and works under the same principles that our manual electrophysiology experiments do. Its taken a while to get it up and running; I’m the only PhD candidate in lab responsible for our electrophysiology experiments and learning how to program the robot often takes a backseat to my project. Plus, the last time I coded in java was while I was attending Dodge City Community College 7+ years ago. Still, I’ve made a lot of progress in optimizing the robot, and have even started optimizing another system we have, the Roboinject. It injects oocytes for us, and what’s cool is that it can inject things separately; I usually mix the RNA so that we only have to do one set of injections, but with the Roboinject, we can optimize the settings more easily by adjusting the volumes independently of one another. Down the road, I would like to the cells inject peptides, in addition to DNA and RNA.
Long story short: learn from the negative experiences, but don’t let them make you suffer. Good science is tough to do (it’s a marathon not a race); make sure take your mind off things so you don’t burn out.
*PI stands for principal investigator; it’s the professor who is my academic advisor and who’s lab I work in.
