Prof. Ian Robinson of the London Centre for Nanotechnology (LCN) has been awarded a 5-year ‘Diamond Fellowship' by the BBSRC. The fellowship will be located at the new Research Complex at Harwell (RCaH) in close proximity to the Diamond Light Source, the UK's premier X-ray facility. He will establish a group in the RCaH to work on the structure of the chromosome using X-ray diffraction methods. Prof. Robinson will join Prof. So Iwata whose group is already in residence at the RCaH, studying membrane protein crystals.
Although much is known about the chromosome, which is the repository of all genetic material in eukaryotic forms of life like humans, still there is a big gap in the knowledge of the structure of these complex molecules in the range from about 30nm to 500nm (one nanometer, or nm, is a millionth of a millimeter). Below this range, traditional X-ray diffraction provides detailed atomic structure, while above this range, visible light microscopy takes over.
During the process of mitosis, the cell separates the chromosomes in the nucleus into two identical sets, in preparation for cell division. There are several phases during mitosis, and it is precisely in this process that the behaviour of the chromosome structure on the intermediate nanoscale, which has so far been difficult to study experimentally, becomes of key importance to the safe transmission of all the genetic material to progeny cells.
Prof. Robinson is a pioneer in the field of coherent X-ray diffraction, which unlike light microscopy methods, can obtain the structure of a material using a computational algorithm rather than a lens, and which is not subject to the so-called ‘phase problem' that leads to uncertainties in extracting structural information from traditional X-ray diffraction techniques.. Coherent X-ray diffraction has been demonstrated for nanoscale materials in recent years by the Robinson group at LCN. Diamond's new I-13 beamline will have world-class capabilities for this sort of research and will be readily accessible to the RCaH.
It is within this intermediate level of structure of the so-called metaphase, one of five phases of mitosis, where the organization becomes complicated (see Fig. 1). To protect the genes in transit though mitosis, they are packed together tightly into the familiar X-shaped chromosome pairs that separate once the cell division begins. The 30nm fibres are presumably coiled up in a regular superstructure at the next level within the chromatids; this coiling is the structure that Prof. Robinson and his colleagues intend to image by the new coherent X-ray methods.
Figure 1. Left: : ribbon diagram of the structure of the nucleosome. Right: model of the 30mn chromatin fibre obtained by cryo-electron microscopy [from D. Rhodes et al, PNAS 103 6506-6511 (2006)].