“Why get up in the morning and fight for grant money and all this? We get to see things that no human has seen before and learn stuff that’s not in any textbook. We get to work with talented students…and watch them grow into scientists!”
This is what excites Dr. Shawn C. Little, PhD., a newly appointed Assistant Professor in the Department of Cell and Developmental Biology at the Perelman School of Medicine.
Shawn is no stranger to Penn. He completed his doctoral thesis with Dr. Mary C. Mullins in 2008,on the role of transforming growth factor beta signaling in early zebrafish development. His work elucidated how bone morphogenetic protein gradients conferred cell fate and gene expression patterns to shape the dorsoventral axis during early embryogenesis.
Shawn built on this research as a postdoc in the lab of Dr. Eric Weischaus (in collaboration with Dr. Thomas Gregor) in the Physics department at Princeton University. While at Princeton Shawn looked deeper into how gradients and pattern information are reliably arranged within the embryo. He was additionally interested to know how subtly changing the timing and levels of transcription factors and signaling gradients can elicit specific gene expression patterns.Together with the Gregor lab, Shawn developed a novel method for imaging and quantifying single messenger RNAs (mRNA) in Drosophila melanogaster embryos. This fruitful collaboration resulted in many publications and unearthed new insights into the transcriptional dynamics and mechanisms governing reproducible gene expression patterns.
Now in charge of his own lab, Shawn intends to study the facets of gene expression control that generate specific patterns and programs of transcription during embryogenesis.
Shawn elaborates, “the embryo needs to elicit a specific set of gene expression programs as a function of position. [In the cell] you have molecules that bump into each other at random, so how is it that at a given position, a set of cells can simultaneously decide to express a specific set of genes? At a biophysical and mechanistic level, how do enhancers and promoters at genes read input concentration levels to generate these specific responses as a function of position?”
To get at these questions, Shawn’s lab uses his newly-pioneered single mRNA imaging technique as well as the live imaging of transcriptional reporters to know at any point in time how many mRNAs are being produced, how many polymerases are transcribing a gene, and how clustered these polymerases are (also known as transcriptional bursting). The lab studies how these singular bursting events are coordinated to establish a precise gene expression pattern.
Shawn is also excited to expand his studies through the many opportunities for collaboration at Penn. He feels that Penn has the best of both worlds: a vast basic sciences network and a medical school. This, in combination with the many experts here at Penn, “gives you an immediate sense that you use your questions to benefit human health,” he says. Shawn’s academic and intellectual curiosity is also reflected in his journey to becoming a professor. He describes his path to academia as “fairly meandering.”As an engineering undergraduate at Northwestern University, Shawn felt somewhat bored with engineering classes, so by chance he began working in the lab of Dr. Doug Engel studying cell fate during hematopoiesis. This experience ignited his interest in changes in gene expression underlying cell fate decisions. However, it was while he was a technician in the lab of Dr. Adam Driks at Loyola University that Shawn really noticed what the other labs around him were doing and began to seriously consider a career in academia.
His path led him to the graduate program at Penn for Developmental Biology. Shawn had a very successful graduate career and said that he felt lucky to have found the Mullins lab, which he described as “allowing me to apply the techniques I’ve acquired and…overall, a great fit.” One of Shawn’s favorite moments from graduate school was of an epiphany in the lunchroom. A few labmates were struggling over a set of uninterpretable results for months with no luck. Finally, after drawing out diagrams on the board, “we had a simple model that explained a complicated idea. Everything just clicked!” said Shawn.
However, his transition from graduate student to postdoc to faculty member was not easy. Shawn was challenged to develop his multi-level thinking abilities. He had to come up with broad enough questions that many people can work on, while being simultaneously specific enough to generate publications. He also felt a hurdle in the shift from a single-focus mindset to being an effective and efficient multi-tasker. This change made him realize how amazing the faculty who mentored him really have been, and is something he admits he is still working on. Another challenging experience for Shawn was the switch from being a primary data-generator to a manager. He emphasizes that learning how to respond to different needs, i.e. tailored mentoring strategies and conveying concepts across diverse audiences, is critical for success.
Despite these challenges, Shawn seems to relish the mentoring aspect of being a PI. He finds training students, especially those who have never worked in a lab outside of class, a rewarding part of being a faculty member. He finds nothing more exciting than to see how rigorous work skills are developed and how students learn to come up with a framework to interrogate hypotheses. To students interested in pursuing academia, Shawn attributes his own achievements to taking lessons from failure, persevering, and not letting failed experiments affect his attitude since “one way or another, things work out.”
Shawn strongly recommends stepping out of your comfort zone and choosing a lab where you’re excited about the science and the kinds of questions asked.
He believes that you should “always be willing to question what is presented to you even when the answers seem obvious. How were the facts established? Questions we think we know the answers to, we may not actually understand them at all. Look to [your] role models in academia and try to draw things from each person, what you like about how they do an aspect of their job. Working on an idea that you think is interesting is the main driver of success, and will lead other scientists to also think your question is interesting and worthwhile pursuing.”
Dr. Little is happy to speak to you about rotations! If interested, please email him at shlittle@pennmedicine.upenn.edu. For more information of Dr.Little and his lab, please visit his lab’s website here.