Advancing Robotics for Structural Biology

There is not yet a commercialized instrument to enable fully automated and remoteaccess sample exchange for crystallography under controlled humidity conditions. Today synchrotron beam lines are highly automated. When cryogenic samples are used, robots rapidly exchange samples; and most researchers conduct experiments remotely. Remote-access experimenters ship samples at cryogenic temperatures to the synchrotron and then control all aspects of their experiment remotely by accessing the beam line control software and video systems through an internet connection. Remote experimenters save time and money because they do not need to travel to the synchrotron; and the supporting automation enables them to accomplish more science in less time. However, this automation is not compatible with samples that are not cryo-preserved. Unfortunately, cryopreservation can alter details of the molecular structure and makes certain advanced experiments impossible, such as many time-resolved experiments where experimenters aim to visualize macromolecular machines in action. For this reason, there is growing demand for automation that supports remote-access macromolecular crystallography using samples under controlled humidity and near physiological temperatures. Meeting this need is complicated by the delicate nature of the biological samples. For this phase-1 proposal, we will develop a temperature and humidity-controlled sample storage and transport chamber design that extends the capabilities of robotic sample delivery systems, currently only compatible with cryogenic samples, to safety support experiments using samples at near physiological conditions. In collaboration with SSRL, CHESS and ALS staff, we will develop prototypes for testing and feedback that enhance robotic systems currently used at synchrotrons and home laboratories for cryogenic sample exchange. Our instrument will be marketed for use at synchrotrons, academic laboratories and at pharmaceutical companies that use crystallographic techniques for structural biology research. It will simplify studies of biological structure in conditions more closely matching their native environment, to provide new insights to the biological processes that drive life functions. Once understood, we may harness many of these processes to develop new medicines and to carryout green chemistry, driving improvements to our health and our environment.