Grant: Project Grant

Macrophages and dendritic cells engulf microbes to remove these from our bodies. Once engulfed, the microbe is enclosed within an organelle called a phagosome that fuses with lysosomes to acquire degradative capacity. This is because lysosomes are organelles that host digestive enzymes. These cells are also known as antigen-presenting cells (APCs) because they process and present microbial fragments, or antigens, formed during digestion. Antigen presentation activates T cells, which train the immune system to make antibodies against a specific microbe. Thus, antigen presentation is an essential step during vaccination. Lysosomes are globular in resting APCs. APC exposure to bacterial lipopolysaccharides transforms lysosomes into an expanded tubular network that helps APCs take up more extracellular cargo, which improves antigen presentation. Yet, it remains unclear why APCs change the morphology of lysosomes. Since morphological change is a physical phenomenon, we think that biophysical modelling of lysosome networks will help us understand their function and how this evolved. Such models will then aid in generating and testing predictions. In addition, while lipopolysaccharides trigger lysosome remodeling, there are many types of microbe and viral molecules - we want to know if other microbe molecules cause lysosome remodeling. Moreover, vaccines rely on adjuvant substances to improve their efficacy and efficiency - we will explore if these adjuvants remodel lysosomes and if this is important for the role. Lastly, we do not know if and how mRNA vaccines alter lysosomes and if lysosome remodeling is important for their efficacy, which we will investigate. Ultimately, this project uses a multi-disciplinary approach to examine how fundamental processes of information transfer within cells are used to adapt APC function to promote adaptive immunity. This knowledge may then provide tools to help boost the innate immune system and/or produce better and safer vaccines.