Uncovering the molecular networks underlying organismal health and disease

Networks of diverse cells are required to sustain the life of multicellular organisms. These cells are in turn made up of distinctive genetic networks that define their identity, functions, and interactions. These levels of biological organization rely on each other and a single perturbation to a cell’s gene network can have detrimental consequences on the whole system and lead to disease or death. Therefore, studying the genetic networks of a cell in various contexts of health and disease can give important insights into the molecular drivers of disease and identify effective points of intervention. Here, I present three projects that explore the relationship between intracellular gene networks and organismal health. In the first project, we show how the gene adh-1, which encodes an alcohol dehydrogenase, acts downstream of several well-known genetic pathways involved in nutrient sensing and is both required and sufficient to extend lifespan and healthspan in the model organism, C. elegans. We also find that adh-1 is sufficient to extend lifespan in yeast and is induced in response to geroprotective interventions in mice and humans hinting at a conserved role for this gene in promoting longevity. This makes adh-1 a promising longevity-promoting candidate. In the second and third projects, we take a different approach to unveiling the genetic networks underlying animal health and disease. First, we take advantage of recent technological advances and develop new tools to systemically identify, with single-cell resolution, the genetic networks that characterize the functioning of a healthy multicellular organism. In the third project, we use these tools to identify the changes that occur to these genetic networks in the context of disease, specifically diet-induced obesity. We identify common and cell-type specific transcriptional changes and use publicly available experimental data to begin elucidating the role of various genes and the specific tissues in which they are expressed in the development of obesity.