Tissue regeneration has fascinated scientists for hundreds of years. Regeneration can be seen as a complex system of communication between cells, each telling the other what to do and how to coordinate and grow together to make new tissues. Once we understand the messages being sent between cells, we will have the chance to promote productive regenerative communication and speed up new tissue formation by adding our own messages, in the form of signaling molecules, to the mix. This is the promise of pharmacologic intervention to regrow organs.
But how will we know what messages to send? How will we know that cells are receiving messages? First, we need to be able detect when and how signals are received by individual cells. How do cells listen, hear, and interpret messages? Second, we need to identify all the different cell types involved in tissue regeneration and generate a catalog of the molecules each individual cell expresses. With this information in hand, we can identify all the senders and receivers of information and test ideas about how cells coordinate to generate new tissue.
Recently MDI Biological Laboratory has invested in two new powerful technologies to our equipment core that will enable our faculty and visiting scientists to unlock the mysteries of regenerative and aging biology. The first is a Zeiss 980 two-photon confocal microscope. This microscope has the capacity to see deep into the tissue of a living organism and capture images of cells sending signals to one another. The image below is an example of how I am using this powerful microscope in my research. This depicts cells in a living kidney that express a fluorescent calcium biosensor that detects signals in cells that are essential for kidney tissue formation. The red dots that appear and disappear in the image reflect the changing levels of calcium within cells that signal changes in cell shape and function. This technology gives us an entirely new way of visualizing cellular communication and allows us to discover the genetic and molecular basis of how organs are made and what goes wrong during aging or tissue injury.
In addition to new ways of viewing a living cell, we have also invested in new technologies that provide unprecedented ways to characterize all of the different cell types and cell states that are involved in the process of cell development, during the evolution of a disease state, and during regeneration after injury. Known as single cell RNA-seq, this technology allows us to map the genetic and developmental pathways at the resolution of a single cell and monitor thousands of cells for molecules they express.
As we attract outstanding scientists in regenerative and aging biology to our campus, the availability of cutting-edge technology, coupled with the expertise required to design and analyze these sophisticated experiments, will play a critical role in our success. Ultimately these tools will assist scientists in teasing out the answers to complex questions such as, “Why can some species regenerate lost or damaged tissues, while others cannot?”; “How does a regenerative organism know how to regenerate a missing part with complete fidelity to the original?”; and importantly, “How can we harness essential regenerative signals to promote human tissue regeneration?”