Cell Codes Perpetuate Life

Life has diversified since its origin through bottleneck stages that separate successive generations. Each organism develops from the bottleneck stage, typically a single cell, with two distinct stores of information. One is the linear DNA sequence that is replicated during cell divisions. The other is the three-dimensional arrangement of molecules that dictates what is made using the DNA sequence and changes during development but returns to a similar configuration at the start of each generation. These two interdependent stores of information – one replicating with every cell division (grey) and the other cycling with a period of one generation (colors) – coevolve and together can be thought of as forming a cell code for making an organism. This perspective impacts our understanding of evolution and the origins of inherited diseases.

How is the expression pattern of a gene perpetuated?

To understand how the cell code of an organism is set up and transmitted from one generation to the next, we need to ask questions about how processes are perpetuated. Our lab is using the simple worm C. elegans to understand how the expression pattern of a gene is perpetuated. Taking advantage of our recent ability to induce transgenerational epigenetic inheritance, i.e. modify non-genetic aspects of the cell code, our goal is to use reductionist, systems, and engineering approaches to address this question.

To perpetuate even a simple gene expression pattern of on in some cells and off in all others, organisms need to control the equal versus unequal partitioning of gene regulatory information upon cell division and the switch between both forms of cell division. While mechanisms of unequal or asymmetric cell division have been studied in the context of development, much less is known about symmetric or equal cell divisions and how organisms switch from asymmetric to symmetric divisions. Yet, the entire cell code is capable of being divided equally as revealed by the existence of twins and by experimental manipulation. Therefore, we are interested in understanding the mechanisms that enable equal cell division as well as the switch between equal and unequal cell divisions, i.e., how organisms control the partitioning of gene regulatory information between cells.

These studies will begin to reveal the logic of how the information required to build and perpetuate an animal is transmitted across generations.