Woods Hole Recap
One facet I have happily embraced in my transition to laboratory lead is the opportunity to grow beyond my training and establish new research directions. While it is difficult to plan for the future, I must develop avenues for research that can last the next five and ten years. When I was on the job search and considering my research plan, I had identified a big picture question that was very interesting: why does human immune function decline with age? It is not too far a leap to where such knowledge would address the obvious follow-up question: how can we improve aged immune function? While I had received excellent training in the biological techniques required to address the former question, I was unclear of what could be done for the latter. Improving the human immune system falls within the realm of translational biomedicine and the new technologies it entails. But what were scientists doing now, and what is still science fiction? For this, I needed to learn from experts, and I decided the fields of stem cells and regenerative biology would be a great place to start.
Stem cells have the potential to develop into any cell type of an organism. One of the most excellent examples of this is the embryonic stem cell, which incredibly differentiates into a complex body of many different organs and tissues. Given that the sources of human embryonic stem cells are human embryos, which carry many bioethical considerations. Perhaps the next best source is the induced pluripotent stem cell, harvested from mature organisms and can be manipulated back into an earlier developmental stage. Given the possibility of growing healthy new cells from stem cells, it is logical to envision replacing damaged tissues and restoring their functions. Thus, stem cell research is an active field both in academic science and biotech industry. Beyond this potential, though, I was still vague about what could actually be done with stem cells and how I could incorporate them into my immediate research plans. Searching Pubmed for “immune restoration” and “stem cells” produces a broad swath of research, and I found myself lost without any foothold. Thus, I decided to learn about stem cells and regeneration in the classroom workshop setting, and such a course, “Frontiers in Stem Cells and Regeneration”, is offered at the Marine Biological Laboratory in Woods Hole, Massachusetts.
2021 Course attendees, faculty, and TAs.
Woods Hole is an oceanographic institute started back in the 1880s, located in Cape Cod across from Martha’s Vineyard. In addition to its immediate application to marine biology, it has been a site of biological research in fields like embryonic development, neurology, and cellular and molecular biology, as many marine organisms are excellent model systems for fundamental biological processes. It has been the research home of Nobel Laureates. The institute is in a remote village by the sea, south of Falmouth, which lends a special sense of scientific community. I had first learned about the MBL at the beginning of my postdoc when my supervisor sent me to a week-long workshop on microscopy. It felt like going away on a summer camp for scientists, and the experience was new to me and felt special like I was now part of a tradition of scholars.
In perusing the MBL courses I found the Stem Cell course and was delighted to see a familiar name listed as course director, Dr. Jennifer Morgan. For as big as the world of science is and how insignificant I can feel within it, it is amazing to continually rediscover that it is actually a pretty small world. As a graduate student, I trained with a professor in the biology building, and Dr. Morgan was a new faculty on our floor. As an engineering major, I did not have much direct contact with her, but she is such a warm person that she learned who I was, and I recall all the support she gave to my biology colleagues. I had found out that she was now faculty at MBL when I went for my microscopy training, and she took the time to meet with me. I reached out to her again, now 9 years after my microscopy workshop, and she was still the same welcoming person. Explaining my interest in stem cells and regenerative medicine, she thought it would be a great experience for me, especially as an immunologist.
Dr. Jennifer Morgan (left) with Dr. Lancaster
The workshop ran from Sunday to Saturday evenings, and was structured with lectures in the morning, laboratory in the afternoon, and then an evening lecture. One thing that truly surprised me was how much I enjoyed the lectures. I have to admit that I usually zone out pretty quickly if the talk isn’t in my niche interests. However, I enjoyed at least 90% of the talks immensely, took enthusiastic notes (my method of active listening), all the while learning about exotic (non-mouse) model systems with barely any description of immunology. I will recap two of my favorites; interestingly, both were virtual lectures, so I cannot say that I enjoy talks more because they are in person- it is truly the content and the delivery:
Jeff Biernaskie, University of Calgary, “Models to study tissue regeneration” – Jeff introduced us to tissue regeneration and the somatic stem cells that form the non-reproductive tissues. He studies the skin and hair as a model of tissue regeneration, which is aided by our ability to distinguish healthy skin cell regeneration from fibrotic tissue repair during wound healing. The latter half of the talk focused on a fascinating model for skin repair, the velvet of reindeer antlers. It is the only mammalian regeneration of a whole organ, and it occurs every year, at tremendous speed, in the same antler patterning. His description of how the fibroblasts of the velvet maintain regeneration under anti-inflammatory conditions really struck a chord with me, as I am interested in regeneration in the context of aging, which is normally impaired and occurs in chronic inflammatory conditions.
Goro Yoshizaki, Tokyo University of Marine Science and Technology, “Germline stem cell manipulation in fish” – Goro’s research really spoke to me, as he is actively working to solve an important issue in food supply and marine conservancy—and I really love sushi. The wild bluefin tuna is a very popular source for sushi and sashimi, but its population is on the decline. However, because of its long period to maturity (4-5 years) and tremendous size (~100 kg), they are not amenable to farming. Thus the proposal is to ‘grow’ the bluefin tuna from its primordial germ cells within surrogate fish species that are easier to raise, such as the mackerel. The 300-gram mackerel would then produce bluefin tuna spawn upon the mackerel’s reproductive maturity of about a year. But even before tackling this problem, Goro’s lab conducted proof-of-concept using the Chinook King Salmon gametes grown within trout hosts. Though I never thought I would find commonality to fish germ cell research, I was captivated by the scientific crusade and the methodical explanation of a research path spanning over 15 years.
What sets the workshop apart from usual conferences was the opportunity for hands-on laboratory experience across a broad array of techniques. I was very disappointed that we could not do the lab isolating mouse embryonic stem cells from blastocysts; unfortunately, there was a shipping problem and the cells delivered for the lab were not viable. Here were my two favorite labs:
Instructed by Diane Carlisle, University of Pittsburgh, “Human embryonic stem cell differentiation” – I have very little experience with human cells, and so working with a human stem cell line was very exciting to me. To my delight, the protocols themselves are pretty straightforward: I was given a dish of cells, and by introducing different compounds into the culturing medium at prescribed times, the cells would differentiate into the cell type of interest. Much like cooking though, there appears to be an art to it. I was surprised to see what stem cells look like under a microscope—a blob that is so compacted that it is hard to distinguish cell edges. To my untrained eye, I would have thought it was dead debris. For my experiment, I differentiated my cells into cardiac myofibroblasts (mesoderm). Every day I would take a little time to warm the media and change it out in the biosafety cabinets in order to feed the cells. Though I have some experience with cell culture, I also attended the optional cell culture technique introduction, since I worry that I am a little sloppy in my aseptic technique; turned out I was just fine. On the last day, I was able to check on my cardiac cells, and though our fluorescence stain didn’t work out, I was able to confirm with the TA that I had cardiac-looking cells. Very neat!
Human iPSCs differentiated into cardiac myocytes!
Instructed by Kyle Orwig, University of Pittsburgh, “Spermatogonial stem cell transplantation” – The coolest part of the experience was having the opportunity to do microinjections into the mouse testes. Because of regulatory concerns, we were injecting dye into post-mortem animals, but it was really amazing to use the Eppendorf microinjector and micromanipulator, trying to aim these precision devices under a dissection microscope. It was very challenging! The other parts of the lab included looking at preserved specimens of mouse and non-human primate testes, and counting genetically-labeled transplant stem cell colonies within mouse testes under a microscope. The application to fertility science was very interesting, and I just love using new equipment.
Gonads!
Rounding out the workshop experience was the opportunity to socialize with my colleagues, the TAs, and faculty. Meals are during set hours in the cafeteria and also we could sit outside on the nicer days. Scientists love a good happy hour, and we had a few mixer events to relax and meet each other. These are always such good opportunities to connect with other scientists as humans and to feel connected with the global academic community. We did not have much opportunity for free time, usually busy from at least 9 AM to 9 PM, but I did go on runs around the coastline to see the rocky beaches and New England cottages.
Perhaps the cover photo for my upcoming coffee table book on the lighthouses of New England?
Now back in my lab for the past several days, I am still digesting my experience and what it means for my research plans. My immediate concerns are for the lab’s first paper and first grant, and I think that my experience and interest in regenerative science can inform some of those grant aims. At the least, I have made new contacts within the realm of regeneration so I can gather feedback regarding the novelty and feasibility of my ideas.