Work plan

Preliminary work from the HZI identified immune modulators able to revert in part the unresponsiveness to vaccination of aging mice. Thus, murine and human systems (WP2 and WP3) will be exploited to reverse engineer the effector processes affected by these compounds (WP4). This will be complemented by the establishment of a holistic phenomenological in silico model for influenza infection (WP5), which will allow us to understand the dynamics of immunosenescence and pave the road for the translation of this knowledge into improved medical treatments that are tailored for the elderly. The generation of mechanistic and functional hypotheses will be an iterative process intertwining modeling and experimentation, in which the models will be progressively refined with the input of additional in vitro and in vivo data (WP6), thereby enabling the generation of more accurate hypotheses. It is expected that the resulting framework will provide a knowledge base and tools to develop new strategies to optimize responses to vaccination and immune therapies in the elderly.

Work package 1 - Data management and standardization
Lead Alexander Kel, geneXplain

Work package 2 - Evaluation of the effector functions of selected immune modulators on young and aging mice
Lead Carlos Alberto Guzmán, HZI

Work package 3 - Evaluation of the effector functions of selected immune modulators on human immune cells from young adults and aging individuals
Lead Graham Pawelec, TUB

Work package 4 - Reverse engineering the differential responses from immunosenescent cells from mice and humans, and hypothesis generation
Lead Stefan Schuster, FSU

Work package 5 - Holistic modeling of flu infections in young and elderly
Lead Michael Meyer-Hermann, HZI

Work package 6 - In vivo validation and model refinement
Lead Marian Wiegand, AMVAC