Sebastian Doniach

In my current research I’m working with Chuck Yoon’s group at the LCLS x-ray Free electron Laser. Our project is to combine cryoEM imaging of biological molecules where proteins, RNA, or combinations of the two are rapidly frozen, with xFEL scattering patterns of the same solutions imaged in femtoseconds.

In cryoEM the electron microscope real-space images of co-existing conformational states of the molecules are superposed at the time of freezing. In xFEL images the reciprocal space diffraction patterns are superposed in a few 10s of femto secs.

The aim of our research is to be able to study structure-function relationships of bio-molecular interactions by relating conformational changes in time with their functions in living systems. Currently our group is collaborating with Judith Frydman’s group in the Biology Department and the group of Yiorgo Skiniotis in the Medical School on the function of Chaperones. These are large molecules that open to sequester cellular proteins as they are being transcribed by ribosomes, so that they can be released in a functional state. The free energy that drives this process is driven by the hydrolysis of ATP.

The overall motivation for this type of research is to help in the discovery of small molecule drugs that may be able to help intervene in diseases like cancer or Alzheimer’s.