Thematic Research Network SynthImmune

Infectious diseases and cancer pose serious global health challenges. Efficient preventive or curative interventions are lacking in particular for AIDS (Acquired Immunodeficiency Syndrome), malaria and hard-to-treat cancers such as pancreatic and brain cancer. While each of these diseases could be controlled by our immune system, they all evade the immune response by similar mechanisms. Common strategies to gain immune control may thus dramatically improve prevention and treatment of infections and cancer. Yet, interventions to precisely manipulate complex immune and tissue interactions as well as experimental models to study their physiological impact are still in their infancy. Synthetic biology allows the engineering of cells by top-down genetic manipulation or bottom-up assembly from minimal components. This creates unprecedented opportunities to engineer synthetic systems performing complex immune functions and to rationally design tailored intervention strategies. Thus, synthetic immunology has the potential to revolutionize therapeutic approaches to infections and cancer. Recent treatment successes with T cells genetically engineered to express chimeric antigen receptors (CAR T cells) highlight the power of synthetic immunology. However, top-down genetic immune engineering is currently limited to ex vivo applications and subject to complex counter-regulation. 

The TRN SynthImmune therefore aims at establishing a transdisciplinary network for research, education and translation leveraging the assembly of synthetic molecular building blocks in a new field: bottom-up synthetic immunology. SynthImmune aims at comprehensively applying synthetic biology to immunology towards treatment and prevention of AIDS, malaria, pancreatic and brain cancer. This will include the development of new bottom-up synthetic approaches to elicit immune responses, deliver immunogens and tailor immune cell interactions. In addition, it will advance the reconstitution of synthetic cells and microphysiological tissue mimetics to study and manipulate immune reactions. SynthImmune will (i) optimize immunity by functional selection and optimization of rare, highly efficient immune cells, (ii) bottom-up engineer immunity, and (iii) translate candidate interventions by optimization and preclinical validation. In the long-term, we expect these efforts to yield decisive innovations in therapy and prevention of infectious diseases and cancer. Towards this goal, SynthImmune will integrate and strengthen the rapidly evolving research communities at the Heidelberg and Mannheim sites of Heidelberg University and the local extra-University institutions DKFZ, NCT, HITS, EMBL and MPImF as a basis for the future establishment of collaborative research and training networks.