Life as we know it is primarily chemistry: all living organisms are composed of carbon-based molecules such as proteins, carbohydrates, and nucleic acids that are the result of chemical reactions between different elements like carbon, hydrogen, oxygen, nitrogen, and sulfur. Understanding the basic principles underlying chemical reactions is important to understanding life. When thinking about reactions in a chemical context, scientists typically think about reactants interacting in a homogeneous solution that’s essentially the same in any given place. But the cytoplasm, the liquid in cells where biochemical reactions take place, is a biological context that’s quite different from the simplified models of chemistry textbooks. Cytoplasm is a heterogeneous fluid that looks and functions differently across the cell and so it’s not accurately represented by simplifying assumptions of homogeneity. Precisely how these assumptions are distorting our picture of cellular chemistry, and therefore our understanding of fundamental biochemistry, is not well understood. This grant supports Lauren Zarzar and Ayusman Sen at the Pennsylvania State University who will study how solution heterogeneity influences reactivity for three important classes of biochemical reactions. First, they will study autocatalytic reactions, in which one of the reaction products facilitates (i.e. is a catalyst for) the same, or a coupled, reaction. Autocatalysis is a mechanism for chemical self-replication and is considered a key aspect of the prebiotic chemistry that gave rise to life. Next, the team will study enzyme reaction cascades, a sequence of enzyme-catalyzed reactions whereby the product of one reaction is the reactant for the next reaction. They’ll focus on chemotaxis (chemical activity that leads to motion towards or away from a higher concentration of some substance) to study how solution structure affects enzyme cascades. Finally, they will study polymerization reactions and, in doing so, address an important question in prebiotic chemistry: how polymers with specific monomer sequences arise without a specific sequence-directing mechanism. Ultimately, this project will deepen our understanding of specific reactions central to cellular chemistry and shed light on the role solution heterogeneity plays in driving the chemistry of life.