Engineering and biology join forces for healing
How do we control a cell to harness its full therapeutic and medical potential? The answer lies where engineering and biology meet. In our lab, engineering provides the data and analytical frameworks for handling and deciphering how a multitude of signals within a cell integrate to lead to each cellular outcome — the development of a particular tissue or cell type.
This is essentially data-driven “reverse engineering” of a biological system. But engineers also “forward engineer” — taking what we’ve learned, and using the tools and instruments at our disposal to guide cells and their development.
In my lab, we both reverse and forward engineer. We study how an organism develops from a single cell that contains all the information for a given process, and is the source of every cell of every organ and tissue in the body. We look at how cell signaling is controlled in the earliest stages of life to figure out how cells differentiate into the correct types, at the right times, and in the right places as the organism develops. In addition, we are developing ways to use that information to control the process, conducting research that contributes to regenerative medicine, which accelerates healing and repairs bone and tissue.
The signaling molecules we study are basically instructional cues that provide the information that tells a cell what to become. We focus on what are called Bone Morphogenetic Proteins (BMPs). These growth factors bind to a receptor on the cell surface, activating a cell to start turning on and off genes in the nucleus. Different levels of BMPs leads to different levels of signaling and the activation of different genes. This allows the BMPs to specify many different types of cells in a tissue or across an entire developing embryo.
When a single-cell embryo divides, and new cells continue dividing, there are hundreds and thousands of cells spread out that now need information to become different types, based on their position. In early life, BMPs are one of the kinds of molecules that tell each cell where it is, so the cell can start to carry out a new or specific function.
I work at the interface of developmental biology and engineering on this early embryonic development and spatial patterning, using mathematical models, imaging, and tight model/data integration. Our lab looks at how the spatial patterns of BMPs and signaling molecules are formed and controlled. We quantify these processes to see what the patterns look like, which genes are being activated over space, and how these changes take place.
It’s like a Google Earth of an embryo. All of these images are converted into data points for every cell. You can zoom in to see specific gene activation in a single cell, and zoom out to see what the pattern looks like from one side of an embryo to the next side.
We are using artificial intelligence (AI) so the computer automatically will find the different features in an embryo, draw boundaries around them, and quantify aspects within these boundaries like signal strength. As we get more and more data, the AI learns how to find all the features in the images; once it’s well-trained, we can rapidly quantify the images and convert them into datasets for 3D embryo simulations. This is a computationally intensive task, requiring millions of simulations. By training an AI to predict the simulation result, we have sped up calculations by 20,000 to 30,000 times, and we are able to solve problems we never could have envisioned solving.
The field of regenerative medicine seeks ways to control cells and tissues in vivo or ex vivo to replace damaged or diseased tissues. In a sense, we are cartographers –working to plot chemical roadmaps to make any cell, using technology and simulation. Once the maps are filled in with sufficient detail, they can be followed from a starting point to a destination.
A deeper understanding of signaling and signal integration will lead to improvements in regenerative medicine in ways we can’t even begin to imagine. The potential for co-opting these pathways to make clinically useful cells is very high, and early use of BMPs already has improved patient outcomes in bone repair, oral surgery, and dental implants.
David M. Umulis, PhD
Professor and Associate Head for Research, Weldon School of Biomedical Engineering
Professor, Department of Agricultural and Biological Engineering
College of Engineering, Purdue University