Prof Elspeth Garman

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Prof Elspeth Garman

Prof Elspeth Garman

Methods development for structural biology

We aim to enable the 3-D structures of more large biologically and medically important molecules to be found by making an impact on improving current methods in structural biology, particularly (but not solely) those using X-ray crystallography. This work currently includes studies on cryo-temperature and room temperature (RT) radiation damage, modelling the 3-D distribution of absorbed X-ray dose during experiments so that the use of diffracting crystal volumes can be optimised, and similar dose modelling of electron energy loss in samples measured using electron microscopes. Additionally we carry out accurate quantitative analysis of the trace elements in proteins using microbeam Proton Induced X-ray Emission (microPIXE), and are developing this as a high throughput method by printing low volume arrays of proteins using a non-contact printer.

 

Radiation damage to the crystal is an unavoidable problem when using ionising X-rays, even during cryo-crystallographic (~100K) data collections. We seek to understand the physical and chemical basis of the damage, and to find strategies to reduce its rate in order to optimise our data collections and thus maximise the biological information gained. We have carried out various studies on the addition of radioprotectants to protein crystals, and have identified a method to analyse the B-factors of protein structures deposited in the Protein Data Bank for signs of radiation damage. Our widely used software program, RADDOSE-3D ( www.raddo.se ) allows different experimental strategies to be explored. It also makes possible the quantitative inter-experiment comparison of radiation damage metrics as a function of absorbed dose. See http://www.bioch.ox.ac.uk/garmangroup