Nicholson's Application

I currently work in a group which carries out research on electron microscopy of biological macromolecules and makes extensive use of image processing. The group is interested in carrying out single particle reconstruction using large datasets. In single particle reconstruction, the macromolecule (or particle) is present in a number of different views in electron micrograph images. The particle images are aligned using correlation methods and used in a 3D reconstruction. The group wish to apply single particle reconstruction at high resolution. This requires a large number of particles and is computationally intensive. I am assisting with work to port existing single particle reconstruction software to the IBM SP and Cray machines at NERSC. (I have already ported one major software package for single particle reconstruction, called SPIDER, to the Cray J90. Most of the work had already been done by the original developers; as SPIDER had been previously parallelised for use on an SGI Origin 2000 using OpenMP, which is supported on the J90.) At present, single particles are identified manually from electron micrographs (using interactive software), and windowed out in order to obtain particle images. This is human labor intensive when working with large numbers of particles and I am developing software which will automate this task,

PUBLICATIONS

1. A Holzenburg, MC Bewley, FH Wilson, WV Nicholson and RC Ford (1993) Nature 363, 470-472. "Three-dimensional structure of photosystem II".

2. WV Nicholson, L Sawyer, P Taylor, I Dawson and RO Gould (1993) Acta Crystallographica C49, 101-103. "4-Methoxyindan-1-one Oxime".

3. G Muir, RL Jones, SG Will, T Winwick, V Peesapati, NH Wilson, N Griffiths, WV Nicholson, P Taylor, L Sawyer and AJ Blake (1993) European Journal of Medicinal Chemistry 28, 609-624. "Thromboxane receptor active analogues based on the 6-oxabicyclo[3.2.1]octane ring system".

4. WV Nicholson, FH Shepherd, MF Rosenberg, RC Ford and A Holzenburg (1996) Biochemical Journal 315, 543-547. "Structure of photosystem II in spinach thylakoid membranes: comparison of detergent-solubilized and native complexes by electron microscopy".

5. WV Nicholson, RC Ford and A Holzenburg (1996) Bioscience Reports 16, 159-187. "A Current Assessment of Photosystem II Structure".

6. MF Rosenberg, A Holzenburg, FH Shepherd, WV Nicholson, TD Flint and RC Ford (1997) Biochimica et Biophysica Acta - Bioenergetics 1319(1), 119-132. "Rebinding of the extrinsic proteins of photosystem II studied by electron microscopy and single particle alignment: an assessment with small 2D ordered arrays of photosystem II".

7. CJ Gilmore and WV Nicholson (1994) Transactions of the American Crystallographic Association, 30, 15-27. "The MICE computer program and its application to direct phase determination for proteins, electron diffraction and macromolecules".

8. CJ Gilmore, WV Nicholson and DL Dorset (1996) Acta Crystallographica A52, 937-946. "Direct Methods in Protein Electron Crystallography. The ab initio Structure Determination of Two Membrane Protein Structures in Projection using Maximum Entropy and Likelihood".

9. CJ Gilmore and WV Nicholson (1998) "Direct Methods for Solving Macromolecular Structures" NATO ASI Series C Mathematical and Physical Sciences 507, 455-462. "Developments in Maximum Entropy and Likelihood".

10. WV Nicholson, M Lee, KH Downing and E Nogales (1999) Cell Biochemistry and Biophysics 31, 71-83. "Cryo-electron microscopy of GDP-tubulin rings".

MEETINGS

1. Presented a poster entitled "The effects of detergents on the oxygen-evolving activity of spinach PSII membranes" at the Biochemical Society Harden Conference on photosynthesis in 1991.

2. Presented a poster entitled "Computer averaging of electron micrographs of PSII particles" at the IXth International Biophysics Congress on July 1993 in Budapest.

3. Presented paper at the American Crystallographic Association (ACA) Meeting in July 1995 in Montreal entitled "Solving structures from electron diffraction data using the MICE computer program".

4. Presented poster at the EUCHEM conference on Electron Crystallography on June 1996 in Stockholm entitled "Maximum Entropy Methods in Electron Crystallography".

5. Presented poster at the International Union of Crystallography (IUCr) Meeting on August 1996 in Seattle entitled "Phasing the cholera toxin electron diffraction data using the maximum entropy-likelihood method with non-crystallographic symmetry imposed in the MICE computer program".

6. Assisted Clint Potter and colleagues with a research demonstration at the Alliance '98 meeting in Urbana-Champaign entitled "Demonstration of Tele-Immersion Applications for Biological Imaging".

7. Presented poster at the International Union of Crystallography (IUCr) Meeting on August 1999 in Glasgow entitled "Cryo-electron microscopy of GDP-tubulin rings".