Professor Brian Austen is a peptide/protein scientist. His research concentrates on diagnosis and therapy in Alzheimer's disease.
His work focuses on neurotoxic peptides and proteins. Large build-ups (plaques) of amyloid proteins and peptides are found in the brains of patients with Alzheimer's and are thought to be instrumental in the development of the disease. Professor Austen has illustrated the destructive effect of smaller clusters, known as oligomers.
In 2000, he developed complete chemical syntheses of β-amyloids 40 and 42, widely thought to be a major cause of neurodegeneration. He showed that aggregated oligomers of these peptides are toxic to brain cells, and synthesised some novel compounds that inhibit aggregation and prevent toxicity.
His research group have also synthesised a gadolinium-containing contrast peptide for MR (magnetic resonance) imaging that can be used for early diagnosis of Alzheimer's.
He has developed an ELISA (enzyme-linked immunosorbent assay) – a test – that can identify β-amyloid oligomers. With this, he illustrated that there are raised levels of soluble oligomers in the blood of people who have Alzheimer's.
Professor Austen previously found that the cell targeting of the amyloid precursor protein (that generates β-amyloid) was influenced by raised cholesterol and lipid levels inside cells. High cholesterol levels activate the enzyme that releases β-amyloid by lipid modification, and may increase the risk of Alzehimer’s. Professor Austen was the first to suggest statins as protective therapy.
Professor Austen's research group comprises:
- postdoctoral fellow Dr Nick Spencer (studying MRI of 5X FAD Alzheimer’s mice, and use of Gd-linked contrast agents to diagnose Alzheimer’s Disease);
- PhD student Lucy Ly (characterisation of the beta-secretase [BACE-1] complex);
- MRes student Kimberley Kienast (ultrasound and nanobubble-mediated uptake of MRI contrast agents into mouse brain); and
- BSc student Najith Wijesiriwardana (interactions between PMCA2 calcium ATPases and PSD95 scaffold in the post-synaptic membrane).
Publications
2013
NG Spencer, LR Bridges, K Elderfield, K Amir, B Austen, FA Howe. Quantitative evaluation of MRI and histological characteristics of the 5xFAD. Alzheimer NeuroImage. 2013, Aug 1;76: 108–15.
2012
CL Russell, S Semerdjieva, RM Empson, BM Austen, PW Beesley, P Alifragis. Amyloid-β acts as a regulator of neurotransmitter release disrupting the interaction between synaptophysin and VAMP2. PLoS One. 2012, 7(8) e43201.
2011
RB Parsons, S Aravindan, A Kadampeswaran, EA Evans, KK Sandhu, E Levy, MG Thomas, BM Austen, DB Ramsden. The expression of nicotinamide N-methyltransferase increases ATP synthesis and protects SH-SY5Y neuroblastoma cells against the toxicity of complex I inhibitors. Biochemical Journal. 2011, May 15; 436 (1): 145–155.
2010
Balpreet Matharu, Omar El-Agnaf, Amna Razvi, Brian Austen. Development of retro-inverso peptides as anti-aggregation drugs for beta-amyloid in Alzheimer’s Disease. Peptides. 2010, Oct; 31(10): 1866-1872.
2009
B Matharu, G Gibson, R Parsons, TN Huckerby, SA Moore, LJ Cooper, R Millichamp, D Allsop, B Austen. Galantamine inhibits beta-amyloid aggregation and cytotoxicity. J Neurol Sci. 2009, May 15; 280(1-2): 49-58.
2008
Parsons RB and Austen BM. Post translational modifications and cellular targeting of beta-secretase. In: Recent Advances in the Biology of Secretases, Key Proteases in Alzheimer's Disease (ed. Wataru Araki), Research Signpost (Kerala, India) (ISBN 978-81-308-0263-3), 2008.
Favourites
Gibson G, Gunasekera N, Lee M, El-Agnaf OMA, Wright A, Austen B. Oligomerisation and neurotoxicity of the amyloid ADan peptide implicated in familial Danish dementia. J Neurochemistry. 2003, 10; 1471-1480.
Austen BM, Parsons R, Sidera C. Post-translational processing of beta-secretase in Alzheimer's disease. Proteomics. 2005, 5, 1533-1543.
Austen BM ans Westwood OMR. Protein targeting and secretion, In Focus series (ed D Rickwood). 1991, IRL Press, OUP, Oxford, New York and Tokyo.
Brain penetration of an MRI contrast reagent that binds beta-amyloid.
Awarded to BM Austen BM and F Howe.
Alzheimer’s Association (USA)
November 2009 to November 2013, $399,767.
Imaging reagents for the early diagnosis of Alzheimer’s Disease-a pilot study
Awarded to S Williams and B Austen
Alzheimer's Research Trust (UK)
2006 to 2009, £50,000.
Partition of imaging agents into brain
Awarded to B Austen
GE Healthcare
2008, £2,000
The role of farnesylation of the beta-secretase complex in Alzheimer’s Disease
Awarded to B Austen
Medical Research Council (capacity building PhD studentship in dementia)
2007 to 2010, £65,106
Development of Lewy bodies MRI imaging agents for the early diagnosis of Parkinson’s disease and related disorders
Awarded to O El-Agnaf, JM Conlon, B Austen, D Mann
Michael J Fox Foundation
2005 to 2008, $300,000
At St George's Professor Austen works collaboratively with Professor Franklyn Howe in the Stroke and Dementia Research Group.
He also collaborates with:
Dr Ruth Empson, senior lecturer, Department of Physiology, University of Otago, New Zealand;
Dr Pavlos Alifragis, lecturer, School of Biological Sciences, Royal Holloway, University of London;
and Dr Richard Parsons, lecturer in biochemical toxicology, Institute of Pharmaceutical Science, Kings College, University of London.