During a lab meeting earlier this February, I presented a short talk about my research background as a rotating first-year Ph.D. student. I decided to give the talk in reverse chronological order, first talking about a previous rotation project, then shifting to the first research project I did as an undergraduate. After telling a story about the latter, I showed a slide of a screenshot of an email, sent less than 24 hours ago, about the project’s official acceptance for publication in Nature Communications. It was an impressive and celebratory ending, not just for a 10-minute-long talk, but also for a four-year-long journey that started as an undergraduate-postdoc mentorship and evolved into a multi-pronged collaboration across time zones and disciplines.
**From static to dynamic: giving life to proto-tissues**
I was a second-year undergraduate at Northwestern when I joined Dr. Neha Kamat’s lab, whose research aimed at designing artificial cells. It was March 2021, and Northwestern University had just lifted its pandemic lockdown and cautiously transitioned back to in-person activities, including lab research. Dr. Kamat connected me to a postdoctoral mentor, Jan Steinkühler. I didn’t know it then, but that moment marked the beginning of a years-long collaborative journey.
Before I joined, Jan had developed a method for creating a novel “proto-tissue,” a synthetic foam structure that resembled biological tissues. He also showed that this proto-tissue could heal and remodel itself when sectioned with a glass pipet.
Without any outside perturbation, however, the proto-tissue was quite static; the challenge was to find out how this proto-tissue could embody a more lifelike character. After I joined the lab, we tried a few ideas, including an attempt to establish and mimic cell-cell communication. One of these ideas was to encapsulate green fluorescent quorum-sensing bacteria, hoping that we could see periodic flashes of green across the proto-tissue. It didn’t work, but it led us to another lightbulb idea.
With encapsulated bacteria floating around and colliding with the compartment walls, we began to wonder how they were affecting the structure of our proto-tissue. We were inspired by another group who created “microrobots” that could be encapsulated with active particles. This led us to shift our thinking towards dynamic remodeling – a property that gives tissues the ability to reorganize itself – and how one could try to mimic it.
One challenge was determining whether the swimming bacteria had any effect on the structure. Dr. Arthur Prindle, a chemical engineering professor at Northwestern University whose lab had also provided us with the strain of quorum-sensing bacteria, also provided us with active green fluorescent _B. subtilis_ strains. With the help of Dr. Prindle and Peter Tran, a graduate student in his lab, we discovered the headline to our story– that the bacteria indeed had a significant contribution to tissue remodeling.
**An international long-distance mentorship**
Jan finished his postdoc in early 2023 and became a faculty of the University of Kiel in Germany. We continued our collaboration over Zoom calls. Jan began drafting the manuscript and, under his mentorship, entrusted me to create the figures. With both sides juggling other responsibilities, progress was slow but steady, and we submitted our first manuscript in the summer.
At the beginning of August, we received our first good news – an invitation for revision and resubmission by Nature Communications. It was one of our first victories, but it surely was not the last. Indeed, the reviewers were still unconvinced of our data interpretation, and it was still unclear whether our paper would be accepted.
With revisions underway, the first manuscript also presented opportunities for me to grow as a researcher. Using the project as a topic for talks and posters, I attended science conferences such as the American Institute of Chemical Engineers (AIChE) and the Chicago Annual Undergraduate Research Symposium (CAURS).
Another year passed while we worked to address reviewers’ points, and it felt like we were running out of ideas. It was during this time that Mehmet Uçar, who was at the Institute of Science and Technology Austria and a friend of Jan when they were in graduate school at the Max Planck Institute of Colloids and Interfaces (MPIKG), brought us fresh momentum. Mehmet's expertise provided the missing piece to developing a more quantitative data interpretation.
**A ticking clock**
By September 2024, time was running out. I was three months away from graduating, but we needed to collect more data to replicate our experiments. It had been more than a year since I last set foot in the lab, and since then the lab moved to a new building (I lost keycard access and had to knock to get in). We were nearing a submission deadline, for which we had already asked for an extension.
Returning felt less like coming back to an old lab and more like starting in a new lab. Experiments took longer than planned – from figuring out where lab materials were and setting up the microfluidics to refamiliarizing myself with the protocols I wrote up years ago and troubleshooting unexpected results. Over the next few weeks and up until the day I was flying back home, I overcame these obstacles, obtained the data, and left with renewed optimism.
**An international long-distance mentorship, part 2**
After graduating, I took a gap half year in the Bay Area, taking the time to hear back from Ph.D. programs (Jan had written recommendation letters for me), train for a half-Ironman, and travel. Our manuscript timeline was delayed again, and we spent more months over Zoom calls analyzing our newly obtained data, refining our workflow, and revising the manuscript. Now that I had left the lab, computation and image analysis were the only things left to rely on.
The project stayed close to me in more ways than one. As I was writing code for imaging analysis, it was also a topic of conversation with graduate students and faculty I interviewed with. In March, I accepted an offer for a Ph.D. program in bioengineering at Stanford University.
The early-morning Zoom meetings became less frequent, but we made our final refinements and submitted a revised manuscript over the summer of 2024 and a final submission of deliverables at the end of the year.
If I had more time during that lab meeting, that one slide would have told a deeper story – a story of a four-year-long project, filled with twists, turns, obstacles, and victories, and how internal and external forces, like our proto-tissues, remodeled our theories, reshaped our thoughts, and even altered our life trajectories.