ASIP Highlights Session:
I Am An ASIP Member and This Is My Science
- Experimental Biology 2019 – Orlando FL
David Sullivan, PhD
Research Assistant Professor
Northwestern University Feinburg School of Medicine
Sometimes those tacky quotes on motivational posters have a bit of truth in them. That one about journey being more important than the destination seems to fit with the career trajectory of many scientists. It certainly fits with my circuitous route, with more setbacks and course corrections than I care to admit. My particular path has wound through several different model organisms, experimental techniques, and even diverse fields.
As an undergraduate at Indiana University, I joined the lab of John P. Richardson, one of the pioneers from the golden age of molecular biology. The Richardson lab was focused on the structure and function of the bacterial transcription termination factor Rho. The classical training and environment made for a great and formative experience, even though most of my time there was spent trying (and failing) to get simple PCRs to work.
Having cut my teeth on some basic techniques, I decided to jump in the deep end and was accepted to the University of Wisconsin graduate program in Biochemistry. I somehow stumbled my way into the tortuous world of membrane and lipid biochemistry under the tutelage of Anant K. Menon. Frustrations abounded as my love/hate relationship with lipids took me on a humbling, albeit informative, rollercoaster ride of emotion and learning (and some emotional learning). Despite numerous setbacks, which included 6 months chasing a signal that was actually glued from the tube caps, I managed to cobble together a project investigating how cholesterol moves between membranes in the budding yeast Saccharomyces cerevisiae. Although I now have a finer appreciation for the awesome power of yeast genetics and the beauty of biophysics, the real learning, as with all proper graduate studies, could not be found in a textbook. Like so many scientists before me, the true challenge of research is struggling with confusing setbacks and learning how to persevere on the often slow march to positive results.
After graduating, I continued up the evolutionary tree of models organisms and started working with mammalian cells in culture. Under the mentorship of Bill Muller at Northwestern University, I was tasked with biochemically purifying a novel intracellular organelle, the LBRC. It facilitates the migration of white blood cells out of the blood vessel and into tissue and is required for mounting an effective inflammatory response. The LBRC can only be collected from endothelial cells, the major source of which is fresh umbilical cords. Although the purification process was long and arduous, we purified enough to get a vanishingly small but usable amount from ~200 umbilical cords. Out of that process, we were able to identify a handful of proteins, including a large multidomain scaffolding protein known as IQGAP1. We could then perform all the standard molecular techniques in vitro to tease apart its function and examine its mechanism with a line of investigation that continues to prove fruitful.
As knockout mice exist for IQGAP1, we were also able to do some interesting in vivo experiments as well. As expected, mice lacking IQGAP1 had significant defects in several models of inflammation. This led to some truly enjoyable live animal imaging experiments. Using cutting-edge microscopy, we were able to witness white blood cells crawling along the blood vessel and into tissue, which is something that never seems to get old to me. Having established this technical setup, we were then able to expand our live animal imaging to several other interesting topics such as visualizing live parasites in the bloodstream and tracking white blood cells in the meninges after inducing a stroke.
Having started my career with the ‘lowly’ bacterium, I never would have guessed I would someday be making movies of blood cells in a living mouse. Although my path has been unpredictable, what I can say is that ASIP has been and continues to be a big part of it. I think many people view science as a solitary pursuit and envision people toiling away in silence. At least that was my mindset as a naïve undergraduate and graduate student. Becoming a part of ASIP opened my eyes to the broader scientific community and showed me the rewarding world of collaborative science. Belonging to a professional society as supportive and inclusive as ASIP has been incredibly fulfilling for my personal and professional growth. Looking back, I am incredibly thankful that Dr. Muller pushed me to get involved in this supportive and dynamic society.