David R. Brown (neuroscientist)

David R. Brown
File:1205915 scientist.jpg David R. Brown
Born	(1964-09-07) 7 September 1964 Australia
Citizenship	British/Australian
Alma mater	University of Sydney (BSc, MSc, PhD)
Known for	Research on prion diseases
Scientific career
Fields	Neuroscience
Doctoral advisor	Max Bennett

Professor David Ronald Brown (born 7 September 1964, Sydney) is an Australian-born research scientist notable for his work on prion diseases, which include bovine spongiform encephalopathy and vCJD. His most notable research relates to the metal binding of the protein central to these diseases, the prion protein and its cellular role as an antioxidant.

He also served for four years on the British government advisory board on BSE.

Since then Brown has spent more time pursuing research related to other neurodegnerative diseases .

Media Attention

Brown advanced research related to the role of metals in the cause of prion diseases such as vCJD. Media attention focused on this work when claims were made by the farmer Mark Purdey that human cases of vCJD might not be caused by eating beef from cattle infected with bovine spongiform encephalopathy (BSE), the disease in cattle which medical consensus deemed the cause of vCJD in humans. Purdey suggest (among other things) that exposure to manganese. could be responsible. This substance is present in the environment and used in farming. Both Purdey and Brown agreed that exposure to elevated levels of manganese in the environment could increase the incidence of BSE .

Brown's research in regards to manganese showed that manganese causes the protein to change conformation, similar to that seen in prion diseases such as BSE. . Additionally, his research also showed that animals with BSE and humans with vCJD had elevated levels of manganese in their brains, and that prion protein extracted from their brains retained some of this manganese. Brown agreed with Purdey only in as far as the potential for manganese to be a risk factor, increasing the likelihood that BSE or an other prion disease would occur. Brown supported Purdey in his quest to investigate the potential role of manganese in prion disease and this lead to the filming of a program for the BBC in which both Brown and Purdey appeared While Purdey pursued the notion that environmental manganese was a cause of BSE (something that arguably could never be proven), Brown suggested that a chelation therapy to remove the excess manganese from patients with vCJD could be of benefit. While Brown's more conventional research was very well funded, suchchelation therapy for prion disease was never funded despite support for the idea from a number of sources including Charles, Prince of Wales.

Career

David Brown completed his studies at the University of Sydney at the age of 25 and gained the degrees B.Sc. M.Sc. and Ph.D. His doctoral studies were carried out in the Neurobiology Research Centre under Professor Max Bennett and involved research on nerve regeneration.

After completing his Ph.D. he worked for several more years in Australia before moving to the US in 1993 where he worked at the Albert Einstein College of Medicine. He move to Germany and worked at the University of Goettingen where he first began work on the study of prion diseases in the Department of Neuropathology with Hans Kretzschmar. In 1997 he move to the University of Cambridge where he worked independently completing some of his best work. In 2001 Brown moved to the University of Bath. Since 2005 he has been Professor of Biochemistry He consults in this capacity with the media. He is the author of several text books and research papers on prion diseases and serves on the boards of four scientific journals, including the Journal of Neurochemistry.

Personal life

David Brown grew up in the western suburbs of Sydney where he attended Girraween High School. His father, Ronald Brown, was an English migrant and his mother, Margaret Crippin, was a third generation Australian notable for being the first person to survive a fatal form of viral meningitis. His mother was also cousin to the famous Rugby player Arch Crippin. Brown's childhood was marked by frequent chronic illness and poverty.

In 1994 Brown married Regina Buechner in Germany but was later divorced in 2003. He has two children, Lorna Brown and Hadassah Brown.

Further reading

Books

1. Brown, D. R. (2002) Prion Diseases and Copper Metabolism. Horwood Press, Chichester, UK. ISBN 1-898563-87-X.

2. Brown D. R. (2005) Neurodegeneration and Prion Disease. Springer , USA. ISBN 0-387-23922-7.

3. Kozlowski, H, Brown, D. R. and Valensin G. (2006) Metallochemistry of Neurodegeneration. Royal Society of Chemistry Publishing, UK. ISBN 0-85404-360-8.

Important Scientific Articles

1. Brown, D. R., Schmidt, B. and Kretzschmar, H. A (1996) Role of microglia and host prion protein in neurotoxicity of a prion protein fragment. Nature 380, 345-347.

2. Brown, D. R., Qin, K., Herms, J. W., Madlung, A., Manson, J., Strome, R., Fraser, P. E. Kruck, T., A., von Bohlen, A., Schulz-Schaeffer, W., Giese, A., Westaway, D. and Kretzschmar, H. A. (1997) The cellular prion protein binds copper in vivo. Nature 390,684-687.

3. Brown, D.R., Wong, B.S., Hafiz, F., Clive, C., Haswell, S. and Jones, I.M. (1999) Normal prion protein has an activity like that of superoxide dismutase. Biochem. J. 344, 1-5.

4. Brown, D. R., Hafiz, F., Glasssmith, L. L., Wong, B.-S., Jones, I. M., Clive, C. and Haswell, S. J. (2000) Consequences of manganese replacement of copper for prion protein function and proteinase resistance. EMBO J. 19, 1180-1186.

5. Brown, D. R., Clive, C. and Haswell, S. J. (2001) Anti-oxidant activity related to copper binding of native prion protein. J. Neurochem. 76, 69-76.

6. Brown D. R. (2001) BSE did not cause variant CJD: An alternative cause related to post-Industrial environmental contamination. Med. Hypoth. 57, 555-560.

7. Wong, B.-S., Chen, S. G., Colucci, M., Xie, Z., Pan, T., Liu, T., Li, R., Gambetti, P., Sy, M.-S. and Brown, D. R. (2001) Aberrant metal binding by prion protein in human prion disease. J. Neurochem. 78, 1400-1408.

8. Brown, D. R. (2001) Prion and prejudice: normal protein at the synapse. Trends Neurosci. 24, 85-90.

9. Haigh, C. L., Edwards, K. and Brown, D. R. (2005) Copper binding is the governing determinant of prion protein turnover. Mol. Cell Neurosci. 30, 186-196.

10. Lekishvili, T., Hesketh, S., Brazier, M. W. and Brown, D. R. (2006) Mouse galectin-1 inhibits the toxicity of glutamate by modifying NR1 NMDA receptor expression. Eur. J. Neurosci. 24, 3017-3025.

11. Haigh, C. L., Wright, J. A. and Brown, D. R. (2007) Regulation of prion protein expression by non coding regions of the Prnp gene. J. Mol. Biol. 368, 915-927.

12. Alderton, A., Davies, P., Illman, K. and Brown, D. R. (2007) Ancient Conserved Domain Protein-1 (ACDP-1) binds copper and modifies its retention in cells. J. Neurochem. 103, 312-321.

13. Webb, S., Lekishvili, T., Loeschner, C., Sellarajah, S., Prelli, F., Wisniewski, T., Gilbert, I. H. and Brown, D. R. (2007) Mechanistic insights into prion curing by novel anti-Prion compounds. J. Virol. 81, 10729-10741.

14. Brazier, M. W., Davies, P., Player, E., Marken, F., Viles, J. H. and Brown, D. R. (2008) Manganese binding to the prion protein. J. Biol. Chem. 283, 12831-12839.

15. Davies, P., Marken, F., Salter, S. and Brown, D. R. (2009) Thermodynamic and voltammetric characterisation of the metal binding to the prion protein: insights into pH dependence and redox chemistry. Biochemistry, 48, 2610-2619.