Understanding Signal Transduction in Minimal Synthetic Cells

Signal transduction across cell membranes is fundamental to cellular function, influencing processes essential for health and disease. In immune cells, these pathways enable the recognition of pathogens and the activation of immune responses. However, dysregulation in signal transduction is a key factor in many diseases. Replicating these complex mechanisms in synthetic models presents both challenges and opportunities for advancing our understanding of cellular communication. My research group focuses on engineering synthetic immune receptors, along with transporter molecules, to replicate immune signaling with precise spatiotemporal control on the membranes of Giant Unilamellar Vesicles (GUVs). Light serves as a precise external trigger to manipulate synthetic cell functions with high spatiotemporal control, enabling dynamic regulation of gene expression, signaling pathways, and membrane remodeling with minimal invasiveness. By integrating optogenetics and nanotechnology, we aim to reconstruct and study immune cell membrane signal transduction in minimal synthetic cells. Through this bottom-up approach, our research seeks to uncover fundamental principles of cellular communication while paving the way for novel therapeutic strategies.

Expression and Translocation of Functional RNA and Proteins in Synthetic Cells

My other research focuses on developing a cell-free platform for the expression of immunogenic RNA aptamers, peptides, functional proteins, and immune receptors within synthetic cells built from non-living components. This approach provides a powerful tool for studying fundamental gene expression and regulation mechanisms, offering deeper insights into the molecular foundations of life. Beyond expression, we aim to investigate the translocation of larger biomolecules—such as RNA and proteins—across the phospholipid membranes of synthetic cells. A key challenge in synthetic cell engineering is enabling these molecules to move from the inner to the outer membrane, where they can interact with their environment, including targeted cancer cells. By designing mechanisms for controlled molecular translocation, we seek to facilitate direct interactions with cancer cell surfaces, triggering apoptosis via signal transduction pathways. This strategy presents significant advantages for studying protein-protein interactions. Unlike traditional phage display, which relies on viral membranes, our approach allows proteins to function in their native state within lipid bilayers, providing a more physiologically relevant system for understanding molecular recognition and therapeutic applications.

Find this exciting? We welcome applications from motivated, talented, and collaborative individuals at all levels with backgrounds in biology, biotechnology, biochemistry, chemistry, bioengineering, or related fields. Students with their own fellowships are especially encouraged to apply, and we would be happy to host them. Interested candidates can email (tchakrab@em.uni-frankfurt.de) their resume along with a motivation letter.