EXC 3018:  SynthImmune – Engineering Immune Function with Synthetic Biology

• Subject Area: Microbiology, Virology and Immunology ; Basic Research in Biology and Medicine ; Materials Science ; Medicine ; Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics ; Systems Engineering
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 533587280

The human immune system provides powerful protection from many diseases but fails to prevent lethal progression of some infections and cancers. Protective immunity requires immune cells to excel in reaching and specifically recognizing their targets and eliciting effector functions. In rare patients and individual immune cell clones, superior (elite) immune function is mounted that can control even lethal infections and cancers. The molecular basis of elite immunity and the limitations for its selection by natural evolution are unknown. SynthImmune will decode elite immunity and use this knowledge to reconstruct elite immune function from synthetic molecular building blocks (bottom-up) as prototype of new therapies against infections and cancer. To achieve these ambitious goals, we propose to establish an interdisciplinary program for research, education, and translation in the new research field we coined bottom-up synthetic immunology. Synergy will be created by parallel targeting of serious global health problems: hard-to-prevent infectious diseases - AIDS and malaria - and hard-to-treat cancers - brain and pancreatic cancer. These diseases share mechanisms of immune resistance and tissue counter-regulation as well as insensitivity to current genetically engineered (top-down) immunotherapies. The SynthImmune program consists of seven scientific projects, a technology platform encompassing five facilities, and dedicated training and outreach activities. Guided by computational modelling, we will identify key features of elite immunity by characterizing patient-derived or model immune cells selected for their superior activity. This knowledge will be used to construct functional elite immunity modules from minimal components, generated through synthetic biology, nanotechnology, and protein design. In iterative cycles, these modules will be validated in microphysiological organoids and tissue mimetics to inform the development of optimized intervention strategies. The innovative strategy of SynthImmune's will deliver unparalleled insight into the mechanisms underlying elite immune function and conceptualize an entirely new class of synthetic immunotherapies that overcomes the critical limitations of top-down engineering of patient-derived immune cells. The bottom-up approach provides extraordinary versatility and precision in designing therapeutics while enabling cost-effective manufacturing and scaling to make such therapies globally accessible. Dedicated ethics and implementation projects will prepare the transfer of these new therapeutics into clinical application. SynthImmune will integrate and strengthen the dynamic research communities at UHD with a major focus on the interdisciplinary training of young scientists. Building on the unique local research and translational environment, SynthImmune will sustain and expand UHD’s position as international leader in the development and clinical application of bottom-up synthetic immunology.

• DFG Programme: Clusters of Excellence (ExStra)
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Participating Institution: Deutsches Krebsforschungszentrum (DKFZ); European Molecular Biology Laboratory (EMBL); Heidelberger Institut für Theoretische Studien (HITS); Max-Planck-Institut für medizinische Forschung
• Spokespersons: Professor Oliver T. Fackler, Ph.D.; Professorin Dr. Kerstin Göpfrich; Professor Dr. Michael Platten
• Participating Researchers: Dr. Franziska Blaeschke; Professor Dr. Till Bärnighausen, Ph.D.; Professorin Dr. Adelheid Cerwenka; Professor Dr. Friedrich Frischknecht; Viktorija Glembockyte, Ph.D.; Dr. Nora Heinzelmann; Dr. Wolfgang Huber; Professor Dr. Thomas Höfer; Anna Kreshuk, Ph.D.; Professorin Dr. Sonja Loges; Dr. Frauke Mücksch; Professor Dr. Dominik Niopek; Professorin F. Nina Papavasiliou, Ph.D.; Professor Dr. Axel Roers; Privatdozentin Dr. Susanne Roth; Professorin Dr. Christine Selhuber-Unkel; Professor Dr. Joachim P. Spatz; Professor Dr. Georg Stoecklin; Athanasios Typas, Ph.D.; Professorin Dr. Rebecca Wade; Professorin Dr. Hedda Wardemann; Professorin Eva Winkler, Ph.D.