Minimal Phagocyte: A bottom-up synthetic biology approach to studying phagocytosis

Within the intricate landscape of immunology, the captivating cellular process of engulfing external objects, known as phagocytosis, has sparked scientific interest for several decades. This essential process, how for example macrophages devour and engulf bacteria, not only fuels the imagination, but also represents our first line of defense against these pathogens. While phagocytosis is o en recognized for its significance in the human immune system, its scope extends well beyond immunity. The process is for example also an essential feeding mechanism in unicellular organisms and plays a key role in maintaining tissue homeostasis by clearing apoptotic cells. Considering more than ten billion cells undergo apoptosis in a healthy human every day, it quickly becomes clear why phagocytosis is a fundamental biological process. The wide diversity in cells performing phagocytosis and the objects targeted for phagocytosis calls for a diversified set of mechanisms, signalling pathways, and receptors. Despite this diversity, all phagocytotic process converge on the common outcome of particle engulfment, hinting at an overlap in membrane reshaping processes. While our understanding of the process has reached unprecedented clarity, a wide knowledge gap persists. Especially the detailed roles of the cytoskeleton in phagocytosis remain an area of ambiguity. The inherent complexity and underlying redundancy of the process make studying the basic physical principles underlying cytoskeletal remodelling challenging to achieve in living cells. Therefore, aiming to understand the role of the cytoskeleton and the minimal requirements for initiating phagocytosis, this thesis presents a bo om-up synthetic biology approach to studying phagocytosis – the ‘minimal phagocyte’…