Decoding the 3D immuno-metabolic circuitry

The immune system plays a critical role in how our bodies respond to what we eat. In many of our organs and in our blood, metabolism and immunity are inextricably linked, and the connections go both ways — what we eat affects our immune system, and our immune cells change how our bodies process what we eat. When these links are broken or not functioning as they should, diseases like cancer, diabetes, heart disease or neurodegeneration can result. Will Bailis, Chris Bennett and Ruaidhrí Jackson are leading a project to better understand the many links between immunity and metabolism at the scale of individual cells, organs and the entire body. Using laboratory mice, they will study how an animal’s food affects energy production inside immune cells by genetically engineering those cells to “ignore” changes in diet. They will also examine the role of a particular type of immune cell, known as tissue resident macrophages, that exist in all our organs to better understand how these cells govern the metabolism of individual organs and the entire body.

Affiliated Investigators

Will Bailis, Ph.D.

University of Pennsylvania

Will Bailis is an Assistant Professor in the Department of Pathology and Laboratory Medicine at the University of Pennsylvania and the Children’s Hospital of Philadelphia. He received his PhD in immunology from the University of Pennsylvania, where he studied the role of Notch signaling in helper T cell differentiation in the laboratory of Dr. Warren Pear. After graduating, he joined the laboratory of Dr. Richard Flavell at Yale University for his postdoctoral fellowship. During his postdoctoral training, he developed in vitro and in vivo primary immune cell CRISPR screening systems to study how cellular metabolism controls immune cell functional programming. His work demonstrated how distinct modes of mitochondrial metabolism and mitochondrial-cytosolic exchange support the biochemical demands T lymphocytes must meet at a different stages of activation. Now at the Children’s Hospital of Philadelphia and the University of Pennsylvania, Dr. Bailis continues to explore how cellular and organismal metabolism govern cell and tissue behavior and how their dysregulation helps explain disease. A major focus of the Bailis lab is to understand how the spatial partitioning of metabolism (between organelles in cells, amongst cells in tissues, and across the organ systems of the body) controls development and function in the immune system, with the goal of developing metabolite- and diet-based therapies.

Chris Bennett, MD

University of Pennsylvania

Dr. Frederick “Chris” Bennett is an Assistant Professor in the Departments of Psychiatry at the University of Pennsylvania, and Neurology at the Children's Hospital of Philadelphia.  During his postdoctoral training with Ben Barres at Stanford University he created methods to transplant resident macrophages into tissues, and used them to elucidate unique properties of microglia, the brain’s resident macrophages, compared to their counterparts in the blood and body. In his own laboratory, he extends these findings to pursue two related goals: 1) to understand how resident macrophages and their tissue environment regulate each other and 2) to apply these fundamental discoveries to engineering therapeutic macrophages that correct tissue dysfunction, particularly of the brain.  Dr, Bennett received a career transition award from the NIH, the Whitehall Fellowship, and the AFAR junior investigator award.  He is a residency trained psychiatrist and maintains a small clinical practice that greatly enhances his scientific creativity.

Ruaidhri Jackson, Ph.D.

Harvard Medical School

Ruaidhri Jackson is an Assistant Professor in the Department of Immunology at Harvard Medical School. He received his Ph.D. in immunology from the National University of Ireland, Maynooth, where he studied the role of the Pellino family of E3 Ubiquitin ligases in innate immunity under the mentorship of Prof. Paul Moynagh. After graduating, he joined the laboratory of Dr. Richard A. Flavell at Yale University for his post-doctoral fellowship where he studied innate and mucosal immunity. Using reverse genetics, transcriptomics and animal models of intestinal pathology, he elucidated the complex role of IL-18 in mediating both host protection and driving auto-inflammatory disease. Dr. Jackson also discovered a novel mechanism of innate immune cell activation at the mucosa whereby cells utilize mechanosensation to sense their local environment to instigate an inflammatory response. In addition, he also uncovered widespread translation of previously unknown open reading frames during innate immune responses and characterized the functional role of a novel protein encoded by a misannotated long “non-coding” RNA. This work demonstrated a major misinterpretation of the protein coding genome and highlighted the need for a reevaluation of translation during the immune response. Now at Harvard Medical School, Dr. Jackson’s lab continues to explore novel open reading frame translation in overlooked areas of the genome. A major focus of the Jackson lab is to understand how inflammatory signals converge to regulate RNA translation and to identify new mechanisms of translational control during homeostasis, inflammation, and disease.