Dr Mandy Jackson

Dr Mandy Jackson, PhD
RCUK Fellow
Centre for Neuroscience Research
Hugh Robson Building
Edinburgh, EH8 9XD

Telephone: 44 (0) 131-650-7518
Fax: 44 (0) 131-650-6123
Email: Mandy.Jackson@ed.ac.uk

Click here for a printable 1-page CV

Biographical Profile

Dr M Jackson obtained her BSc in Molecular Biology from the University of Edinburgh in 1994 and her PhD from the University of Oxford in 1997.   She then moved to carry out postdoctoral research in the Neurology Department, Johns Hopkins University (1998-2001).   In 2002 she was awarded a Caledonian Research Fellowship and joined the Centre for Neuroscience at The University of Edinburgh.   Dr Jackson became a RCUK Research Fellow in 2005.

Research Overview

Glutamate, the major excitatory neurotransmitter in the mammalian CNS.   It is removed from the synaptic cleft by sodium-dependent glutamate transporters that are located on surrounding astrocytes (EAAT1 & EAAT2) and neurons (EAAT3, 4 & 5).   Extracellular glutamate levels must be tightly regulated to maintain normal neurotransmission and neurodevelopment but prevent neurotoxicity.   Excessive glutamate signalling is though to be central to several neurological disorders including stroke, epilepsy, motor neuron disease and ataxia.   Neurotoxic levels of glutamate can arise from the malfunction of aberrant expression of glutamate transporters.

We identified two proteins (β-III spectrin and PDZRhoGEF) that interact with EAAT4, the glutamate transporter predominantly expressed in cerebellar Purkinje cells.   Both proteins positively modulate EAAT4 cell surface expression and uptake activity.    Recently mutations in the gene SPTBN2, which encodes β-III spectrin, were identified as the genetic cause of spinocerebellar ataxia type 5 (SCA5), an autosomal dominantly inherited neurologic disorder that results in loss of balance and motor coordination.

We used targeted recombination to knock-out the expression of β-III spectrin and found that mice lacking β-III spectrin developed characteristic features of cerebellar ataxia.

Research Direction

Using the b-III spectrin deficient mouse as a disease model we are currently investigating cellular mechanisms that may underlie the mechanisms of SCA5 pathogenesis. One avenue of research is to determine whether changes in EAAT4 distribution and glutamate transporter activity play an important role in the disease process. Other research directions focus on determining whether changes in Ca2 homeostasis, ion channel activity, or vesicle trafficking are involved. Various electrophysiological, molecular and biochemical techniques are being used. By identifying other proteins that interact with b-III spectrin we also aim to better understand the normal function of b-III spectrin and identify other potential cellular pathways that underlie neurodegeneration.

A second research objective is to expand our understanding of the cellular mechanisms that modulate the membrane trafficking of glutamate transporters.

Collaborators

Prof. Jeffrey Rothstein: Johns Hopkins University
Dr Laura Ranum: University of Minnesota
Dr David Wyllie: University of Edinburgh, UK
Dr Mitsunori Watanabe: Hirosaki University
Dr Alastair Lyndon: Heriot-Watt University

Current Grants

Awarded funding from The Wellcome Trust, NIH and Research Councils.

Select Recent Publications

Longhurst DM, M Watanabe, JD Rothstein, M Jackson (2006). Interaction of PDZRhoGEF with microtubule-associated protein 1 light chains: Link between microtubules, actin cytoskeleton and neuronal polarity. J Biol Chem 281: 12030-12040

Ganel R, T Ho, N Maragakis, M Jackson, J Steiner and JD Rothstein (2006). Selective up-regulation of the glial Na -dependent glutamate transporter GLT1 by a neuroimmunophilin ligand results in neuroprotection. Neurobiol Dis. 21:556-67.

Maragakis NJ, M Jackson, R Ganel, JD Rothstein (2003). Topiramate protects against motor neuron degeneration in organotypic spinal cord cultures but not in G93A SOD1 transgenic mice. Neurosci Letts. 338:107-11

Wells CD, MY Liu, M Jackson, S Gutowski, PM Sternweis, JD Rothstein, T Kozasa and PC Sternweis (2002). Mechanisms for reversible regulation between G13 and Rho exchange factors. J Biol Chem 277, 1174-1181.

Jackson M, W Song, MY Liu, L Jin, M Dykes-Hoberg, CI Lin, WJ Bowers, HJ Federoff, PC Sternweis and JD Rothstein (2001). Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins. Nature 410, 89-93.

Lin CI, I Orlov, AM Ruggiero, M Dykes-Hoberg, A Lee, M Jackson and JD Rothstein (2001). Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18. Nature 410, 84-88.

Key Earlier Publications

Jackson, M., Llado, J., and Rothstein, J. D. (2002). Therapeutic developments in the treatment of amyotrophic lateral sclerosis. Expert Opin Investig Drugs 11, 1343-1364.

Jackson M, Steers G, Leigh PN and Morrison KE (1999). Polymorphisms in the glutamate transporter gene EAAT2 in European ALS patients. J Neurol 246:1140-1144

Evangelou N, Jackson M, Beeson D and Palace J (1999). Association of the APOE epsilon4 allele with disease activity in multiple sclerosis. J Neurol Neurosurg Psychiatry 67:203-205
 
For more papers by Mandy Jackson click here.