Periodic Reporting for period 1 - C-CLEAR (Complement: to clear or not to clear)
Reporting period: 2018-07-01 to 2019-12-31
Mammalian complement recognizes a variety of cell-surface danger and damage signals to clear invading microbes and injured host cells, while protecting healthy host cells. Improper complement responses contribute to diverse pathologies, ranging from bacterial infections up to paralyzing Guillain-Barré syndrome and schizophrenia. What determines the balance between complement attack reactions and host-cell defense measures and, thus, what drives cell fate is unclear. The project tries to elucidate molecular mechanisms that underlie the balance between complement attack and host-cell defense, which determine cell fate.
Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far
In the first phase of the project, a series of new experiments have been set up. Significant progress has been made by cryo-EM single-particle analysis and tomography providing new opportunities to reveal key steps in complement activation and defense. Moreover, a new concept is emerging that may indicate a potential mechanism that makes cells more prone to complement attack. Overall the project has had a very good start, but further work is needed and planned to substantiate the stimulating intermediate results.
Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)
We will combine crystallography, cryo-EM, cryo-ET and high-resolution microscopy to resolve complement complex formations and reactions on membranes.