Our ultimate goal is the top-down control of complex biological shape. The first four years of our Center’s primary work will focus on exploiting developmental bioelectricity to understand how cell networks perform the computations that enable them to coordinate their activity toward robust anatomical target states. Transformative advances in birth defects, regenerative medicine, cancer, and synthetic bioengineering require mastery of these mechanisms and computational algorithms.

Reading and Writing the Morphogenetic Code

Learning the rules of large-scale pattern regulation will enable the ability to specify biological pattern and control its remodeling. Current technology and conceptual schemes target the level of the biological "machine code" – they are all about proteins, genes, and cells. The observables and operational parameters at this level do not refer to large-scale shape and do not facilitate its manipulation. Thus, the field faces complexity barriers with respect to rational control of morphology (“what genes must be regulated, in what ways, to change the shape of the hand, or create a new eye?”).

While systems biology seeks to understand emergence of complex form from molecular mechanisms, there is a major disconnect between the plethora of highresolution data and the ability to control patterning outcomes. A complementary topdown understanding of the information-processing and computation carried out by cells during development and regeneration is largely missing. We will address this profound gap by building new tools to exploit endogenous bioelectric pathways that implement high-level pattern homeostasis and control loops. This will greatly potentiate the impact of the existing and future results of existing bottom-up reductionist approaches, and result in highly impactful new capabilities in regenerative medicine and other fields.

We focus on the morphogenetic code: the mechanisms and information structures by which cellular networks internally represent the target morphology, and compute the cell activities needed at each time point to bring the body closer to that morphology. We will of course use the standard work-horses of modern biology: molecular genetics, biophysics, and developmental physiology. However, we will also include new kinds of computational modeling, with techniques from statistical mechanics and AI. One of the key unique aspects of this effort is that it will, for the first time, deal squarely with an informational approach to morphogenesis. Truly understanding and exploiting the morphogenetic code, especially its highly regulative aspects, requires us to understand not only the molecules and genes involved, but also the algorithms and computations that are performed by cell networks in making decisions about anatomical growth and form.

We will specifically address the current lack of conceptual apparatus for asking and answering questions of what patterning systems know, compute, and represent in their efforts to make and maintain anatomical shapes. We will develop new techniques and software for reading, writing, and rewriting the bioelectrical software that mediates between the genome and morphological outcomes. The results of these four years are expected to explore a new frontier at the boundary between biology, physics, and information science, establishing foundational technology and concepts. The next four years, and future efforts, will seek to transition these basic findings into applications in regenerative medicine, cancer biology, synthetic morphology, bioengineering, and unconventional computation.

The Allen Discovery Center at Tufts University is a center of fundamental research on anatomical homeostasis. Dr. Levin and his team focus on reading and editing the biophysical control circuits that underlie the Morphogenetic Code. Explore the concepts outlined in our White Paper, and imagine the breakthroughs to come.