Larry Rodriguez, PhD

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Postdoc Motivation: 101

I’ve been thinking a lot about my postdoc experience and figured I’d post advice, thoughts, and answer questions nobody asked. Title inspired by Jeezy’s TM:101 album, blog written à la Jay-Z’s first verse on “A Million and One Questions/Rhyme No More”, and cover art from Netflix’s “Squid Game.”


Should you do a postdoc?

Similar vibes tbh.

I don’t know? The only people that should do postdocs are people that absolutely need to do postdocs. Like everything academia: caveat emptor.


Is a postdoc really that hard?

If you’re doing it right, then yeah kinda. Postdoctoral life work is tough; that’s by design. The best way to describe my experience is that I’ve been asked to do another PhD, except faster and more difficult for a marginally higher salary. Freedom/autonomy is variable, since for some of the established projects that I work on, the experiments are carved out. That said, on projects that I lead, I can take the lab into new directions. As such, there’s definitely more pressure and responsibility; I would say that if you’re having more breakthroughs than breakdowns, that’s possibly a [pyrrhic] victory. FYI, people I have talked to seem to think that 1-2 first-author publications per year is a decent postdoctoral publication rate. Wow. I mean I get it, but damn. Really though?? During a pandemic? YES; especially during a pandemic for some academic reason.

tl;dr yeet them papers or get yeeted out of academia


Why am I doing this again???

I’m comfortable with in vitro pharmacology, molecular biology, and biochemistry, but I wanted more training in translational science, and patch clamp electrophysiology is the gold standard as far as ion channel drug discovery goes. Plus I’m getting a crash course on neuroanatomy/neurocircuitry while working with other neuroscientists to understand the physiology behind behavior. Like an optogenetics experiment; its lit. Also, a small part of me wanted to prove that I could do patch-clamp/neuroscience, soooo ¯\_(ツ)_/¯ .


Why not go straight into industry??

I’ve always had a clear picture of what kind of scientist I wanted to be, and you would be hard-pressed to find a PhD experience that includes training in every component I’m interested in, so I’m a postdoc now. Put another way, my PhD trained me for the Pre-Pre-IND stuff, and my Reg Sci Master’s taught me about the IND to Post-NDA process; my postdoctoral training fills in the [IND-enabling] gap.

Ardem Patapoutian at a Nobel prize celebration outside the faculty club at Scripps.

Also, Scripps is kind of a big deal in drug discovery and science in general. Case in point: Ardem Patapoutian was recently named one of the 2021 Nobel prize winners in Physiology or Medicine, and a few months before that, Vividion was acquired for >$1Billion. These data suggest that Scripps is a promising environment (biotech beach is right there.)


What have I learned??

Patch-clamp electrophysiology, first and foremost. I’m not a rockstar (i.e. you get >6 cells patched to completion every day IMO) but I can consistently get 3+ cells a day without [too much] cursing while collecting samples for downstream processing and thinking about the results/next steps.

More than anything, I’ve become hyper-aware of the limits/bottlenecks of some very advanced techniques I only dreamed about doing during my PhD. For mass spectrometry/proteomics, its detecting membrane receptors. For genomics, its recognizing that the importance of signaling cascades/PTMs is lost and that protein expression is only possibly approximately correlated (at best) with gene expression. For patch clamp electrophysiology, it’s a lot of things; cell-typing, experimental design, and throughput are all challenges that can invalidate your results if you’re not careful, so you better know what you’re doing, and more importantly, why. For animal studies, its that you lose the ability to ask fundamental questions a model system could answer (with questionable physiological relevance.) For single cell -omics, its freaking everything; oh my god.


How is my training going??

If you factor in a pandemic, good I guess?? I’ve definitely made progress in the areas I wanted to when I started this position. In a real-life drug discovery campaign, I could see myself working on in vitro assay development, e.g. recognize when you would want to use traditional HEK293 cell culture (high throughput, without or without an electrophysiology component; can study non-ion channel targets with BRET) vs two electrode voltage clamp electrophysiology (producing big currents; a more robust system than HEK cells; cheaper than manual in vitro patch-clamp electrophysiology.) I could design/manage a lot of the molecular work (cloning, mutagenesis, transfection, cell culture, functional/pharmacological receptor characterization.) I could also work with on IND-enabling animal studies (patch-clamp electrophysiology) and/or test a hypothesized mechanism of action with next gen sequencing, proteomic analyses, and RNAscope.


What does my day look like?

Every morning I get up at 4am and workout from 5:30-7:30am(while reading papers and planning experiments!!) I head to lab at 8:30am, and work as efficiently as possible from 9am-5pm (working long hours isn’t always efficient!!!) I have good lab technique and again, I plan the day’s/week’s experiments each morning, so when I get to lab I can just (physically) focus on completing the immediate goals (recording from neurons; collecting tissue punches) while thinking about what the data mean, big picture. I can technically stay in lab longer, but after 5pm, you’ve been incubating slices for >8 hours ex vivo, which probably means that the cells in your brain-slice (and probably your actual brain!) are either dying or dead, and I’d rather not have to worry about that in my analysis. I think that if the quality of the work you’re producing is good enough, you shouldn’t have to stretch yourself too thin.

That doesn’t mean I automatically leave at 5pm no matter what; that means that if I’m staying past 5pm, it’s going to be for a very good reason, like a deadline or a pressing question (not because I started ephys late or because I want to break the lab record of drug applications.) I’d say it’s a pareto split at worst; 80% balance, 20% crunch. However, when its crunch time, I take inventory of the effort spent, and do my best to reclaim that time doing something that interests me, like keeping up on drug discovery news (Twitter is great for this) and/or reading cool papers that are unrelated to what I’m working on (PROTACS, gene therapy, drug trials, etc.) It’s the only way I know how to prevent burnout, while consistently doing high level work. Plus, I owe it to myself (and others!!) to do right be me. Grad students and postdocs joke about the value of their time (cheap labor; look at salaries!) but I refuse to play into that trope.

Tl;dr work smarter than harder until you have to.


How am I getting through this???

By setting boundaries and NOT drinking the academic Kool Aid; I cannot emphasize that enough. Our lab studies stress systems and addiction, and after a long, stressful AF electrophysiology campaign (>5 weeks) I’m mentally exhausted. I fight the urge to binge eat/drink by going running at the end of my workout each morning. My PI jokes that I should take a day off from working out to relax, but the truth is, I would not be able to cope with the stress of doing science without working out for 2 hours a day. Seriously, I’m writing this on my exercise bike at 6am right now. On the other hand, I probably wouldn’t need to workout so much if I wasn’t stressed all the time, so again, ¯\_(ツ)_/¯.

My thoughts: if a lab prevents one from working out* everyday, one should simply quit that lab.

* working out, camping, spending time with family; whatever sparks joy