The Project
Investigation and experimentation to better understand apoptotic cell death and immunity.
Winner
Matthew Albert
Institut Pasteur & INSERM
Laboratory of Dendritic Cell Immunobiology
Department of Immunology
Paris, France
www.pasteur.fr
American Matthew Albert, 34 years old, is Director of Research INSERM and Head of the Laboratory of Dendritic Cell Immunobiology at the Institut Pasteur, Paris, leading a team in the area of dendritic cell immunobiology and tumor immunity. He graduated from Brown University, Providence, RI, USA in 1992 with a B.Sc in Chemistry, followed by a Ph.D in Immunology from The Rockefeller University, New York, USA, in 1999 and M.D. in Medicine from Cornell University Medical College, New York, USA, in 2000.
Award
€1,199,196
Apoptosis(*) is widely recognized as the primary mechanism whereby physiologic and pathologic cell death occurs. For immunologists, it has become increasingly clear that death is not an endpoint, but the beginning of an immune response - dying cells influence the immune system through the delivery of antigen for MHC presentation and the modulation of cytokine production.
In order to dissect the ways in which dying cells influence the regulation of immune activation versus tolerance, we must clearly define the path taken as a cell moves from among the living to its final resting place within a phagocyte. Specifically, this project will examine the dying cell as a source of exogenous antigen for dendritic cells to generate MHC I /peptide complexes, a pathway called ‘cross-presentation.’ It will be a priority to determine the nature of the signals provided by CD4+ helper T cells, which seems to be one determinant in the immunologic outcome of cross-presentation. In addition, the death pathways themselves will be investigated as an upstream event, which influences immunity. Apoptotic cells triggered to die via a death receptor pathway versus a mitochondrial death pathway will be characterized for their effect on the immune system. Further, cytokine array technology and transcriptional profiling will help to reveal the distinct instructions offered to DCs.
Though careful experimentation in human and mouse models, we aim to uncover the distinct effector pathways that govern the dendritic cells’ decision to trigger cross-priming versus cross-tolerance CD8+ T cells. This insight will result in a better understanding of how to harness the immune system for tumour immunotherapy as well as define novel mechanisms by which tumours and viruses actively evade the immune system.
(*) Definition - Apoptosis:
In biology, apoptosis (from the Greek words apo = from and ptosis = falling, pronounced ap-a-tow’-sis) is one of the main types of programmed cell death (PCD). As such, it is a process of deliberate suicide by an unwanted cell in a multicellular organism. In contrast to necrosis, which is a form of cell death that results from acute tissue injury, apoptosis is carried out in an ordered process that generally confers advantages during an organism’s life cycle. For example, the differentiation of human fingers in a developing embryo requires the cells between the fingers to initiate apoptosis so that the fingers can separate. The way the apoptotic process is executed facilitates the safe disposal of cell corpses and fragments. Since the beginning of the 1990s, research on apoptosis has grown spectacularly. In addition to its importance as a biological phenomenon, defective apoptotic processes have been implicated in a very wide variety of diseases. Too much apoptosis causes cell-loss disorders, while too little results in uncontrolled cell proliferation, namely cancerous tumours. (Source: Wikipedia)
