How does our immune system protect us against all of the infectious agents and foreign substances we encounter? Much of the answer lies in antibody diversity.  In his first talk, Dr. Hidde Ploegh explains how B cells shuffle their genetic material such that regions of the immunoglobulin protein are rearranged. This generates the antibody diversity needed to recognize an almost infinite number of antigens. Interactions of B cells with T helper cells results in the formation of structurally distinct classes of immunoglobulins, further increasing antibody diversity.  T killer cells are primed to attack infectious agents when immunoglobulins on their surface recognize antigens presented by the major histocompatibility complex (MHC). Ploegh explains that by subverting the MHC pathway, viruses and cancer cells can evade the immune system.

Dr. Helen Piwnica-Worms provides a historical perspective on cell cycle regulation and outlines important experiments in frogs, clams, and yeast that revealed crucial mediators of the cell cycle. Scientists observed that there were factors that allowed cell cycle progression, while there were other factors that prevented the cell from going backward. Using these model organisms, scientists were able to characterize the activation of the inducer of mitosis, the M-Phase promoting factor, which is a heterodimer between cyclin-dependent kinase (Cdc2/Cdk1) and cyclin B.   

Piwnica-Worms explains how scientists have used their understanding of the cell cycle regulation to generate targeted cancer therapies. The cell has proteins that serve as cell cycle checkpoints, which allows the cell to respond appropriately to DNA damage. Although not all of the checkpoints are functional in a cancer cell, these cells still need the checkpoint proteins to respond to DNA damage. Piwnica-Worms’ laboratory studies the use of combining DNA damage agents with checkpoint inhibitors to selectively kill cancer cells. Her laboratory developed a patient-derived xenograft mouse model to study Triple Negative Breast Cancer (TNBC), and predict how the genotype of the tumor affects treatment.

Dr. Shiv Pillai provides a historical perspective on the current model of how the immune system works. Scientists observed that the body produces molecules (antibodies) that recognize the entry of foreign particles (antigens). He outlines the different models of the structure and functions of antibodies and explains the process by which antibody diversity is generated during B cell development (VDJ recombination). B cell development also involves two checkpoints to ensure the generation of functional antibodies and prevent the recognition of self-structures.

Pillai explains how earlier in his career he discovered that two surrogate light chains bind to the heavy chain in pre-B cells to create the pre-B cell receptor (pre-BCR). He showed that binding of the surrogate chains facilitates the formation of the pre-BCR that is needed for B cell development. Pillai demonstrated that the pre-BCR signals through Bruton Tyrosine Kinase (Btk). Patients with non-functional Btk manifest signs of immunodeficiency and deficiency of B-cells in the blood, which shows the importance of pre-BCR signaling for proper B-cell development.

Pillai explains IgG4-Related Disease (IgG4-RD), a chronic inflammatory condition characterized by elevated numbers of T cells and IgG4 secreting plasma cells in the affected tissue. Using tissue samples from patients with the disease, his laboratory isolated and characterized the CD4+ T cells associated with IgG4-RD. Furthermore, he explains how the crosstalk between these CD4+ T cells and B cells is important for IgG4-RD development, and showed that depletion of B cells improves the outcome of the disease.  

Before 1977, all life on Earth was classified into two groups: single-celled microorganisms and complex cellular life such as fungi, plants, and animals. A seminal discovery in 1977 rewrote the tree of life and introduced a whole new domain of organisms known as the archaea - mysterious microbes that are genetically distinct from bacteria. Fast forward to the 21st century, and again new discoveries about archaea are leading scientists to reshape the tree of life and rewrite the evolutionary history of complex organisms. Dr. Dipti Nayak introduces the fascinating organisms known as archaea and explains how they are helping scientists answer the question Where do we come from?.

What if we could understand the human cell in such detail that we could paint an accurate representation of a cell’s molecular organization? In this lecture, Dr. Manuel Leonetti outlines the different genome-wide approaches that scientists are using to build a complete map of the human cellular architecture. Understanding protein networks and localization could aid our quest to understand human biology and disease.

Dr. Ruslan Medzhitov provides an overview of the field of inflammation and outlines its role in pathology and homeostasis. Medzhitov explains how Inflammation is generated when pathogens, allergens, or other perturbations are recognized by sensor cells that then release inflammatory mediators (cytokines and chemokines) to activate effector cells. Inflammation is then followed by a resolution phase that brings the system back to homeostasis.

Why do we experience fatigue and loss of appetite, as well as other symptoms when we get ill? Sometimes what we associate with a pathogenic response and illness is the effect of inflammation. In his second talk, Medzhitov outlines the symptoms that we often feel when we get sick, like the lack of appetite (anorexia), and unveils the molecular mechanisms that explain why we have evolved this way. In addition, he compares and contrasts how anorexia affects the outcome of bacterial and viral infections.