We are all composed of a diverse community of cells, which in turn are made up of a complex universe of biochemical molecules. Somehow, out of that sea of chemistry and soup of cells emerges the person reading this. For humans, the stuff we’re made of is extracted from the food we eat. That food is then spread throughout our bodies to our cells, who use that material to grow and function. In this way, our diet, our bodies’ metabolism, the metabolism of our cells, and how our bodies function are inextricably linked.
…the Bailis Lab aims to unravel how metabolism dictates human health by controlling the behavior of our cells and tissues.
It has been nearly 20 years since the human genome was sequenced. This heroic effort has resulted in the identification of more than 20,000 protein coding genes and over 40,000 non-coding transcripts. Despite this work and hundreds of genome-wide association studies, we still lack simple genetic explanations and curative treatment for far too many diseases. We believe that this discrepancy in genetic knowledge and clinical outcome stems not from a poor understanding of the genome or genetic regulation, but that we have largely overlooked how a more ancient and fundamental aspect of biology underlies human health: the metabolic regulation of cellular and organismal biochemistry.
We traditionally think of cell state (i.e. whether a cell is a skin cell or a liver cell, a resting or inflammatory immune cell, a living cell or a dying cell) as driven by how cells relay information from their environment to their DNA, a process known as signal transduction. This paradigm for understanding how cells process information is shaped by our appreciation of the “Central Dogma” of biology. The Central Dogma states that the information necessary for life is maintained by DNA, which serves as a template for creating RNA, which in turn acts as the blueprint for all the proteins that carry out the work of a cell. Within this context, life and cell state are maintained by three classes of molecules: DNA, RNA, and protein. Accordingly, research has focused on understanding how the relationship between these three sets of molecules underlies human health and disease.
While the appreciation of the Central Dogma and the study of signal transduction have been the basis of most major advances in biomedical research, we have largely overlooked the fact that DNA, RNA, and protein are all composed of smaller biochemical units: nucleic acids and amino acids, respectively. These molecules by definition must predate life itself. It then follows that the rules that govern how these fundamental molecules are generated and interact with one another must be incorporated into every stage of evolution that life has been selected on. We seek to test hypothesize that the metabolic pathways that connect these molecules form the most ancient and essential information processing systems used by life. Though they are less durable than the networks composing the Central Dogma, these biochemical pathways define the boundaries of what a cell is capable of in real-time and what near-term states it is equipped to adopt.
The goal of our research is to begin understanding the logic of how these biochemical networks are organized determines human health – both through the reactions they participate in and how they are compartmentalized within and among cells. We believe this perspective will open new avenues for designing metabolism-based therapies for treating disease and help illuminate why so many pathologies cannot simply be explained by genetics. Unlike therapies targeting signal transduction, which often entail antibody- or protein-based therapeutics that are expensive to develop and require sophisticated infrastructure to produce, metabolites and their derivatives are less costly to generate and have more modest manufacturing demands. This offers the potential to vastly expand both treatment access and the affordability of care. Our group aims to actively leverage our basic mechanistic findings into novel treatments and diagnostics for human disease.