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Dr Shelley Allen-Birt

Dr Shelley Allen-Birt

Dr Shelley Allen-Birt
B.Sc.(Sur.)Hons 2:1, Ph.D.(Lond.)

Senior Lecturer in Medicine

Area of research

Neurotrophins and Neurodegeneration

Office 2.13
2nd Floor,
Learning and Research, Southmead Hospital BS10 5NB
(See a map)

+44 (0) 117 41 47901

Summary

Our group is interested in the underlying molecular mechanisms of Alzheimer’s disease pathology. We have a series of linked projects into the production of amyloid, the genetic and environmental influences on this, and the early changes in Alzheimer brain, including changes in growth factors and their receptors.

NGF binding to TrkAIg2We are particularly interested in the tyrosine receptors TrkA and TrkB, and their respective ligands nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). NGF and BDNF are neurotrophic factors which support the connections between the cholinergic basal forebrain and the hippocampus. These are brain regions which are responsible for formation of new memories and are adversely affected early in Alzheimer’s disease. BDNF additionally has a vital role in memory formation via facilitation of long term potentiation.

One of our studies has previously shown that only one domain of the Trk receptor is required for binding its ligand (NGF or BDNF); that is the immunoglobulin-like domain closest to the membrane (Ig2). By comparison of the structure of the TrkIg2 domains in complex with their ligands we were able to identify hotspots on the receptors required for specific ligand binding.

By developing this work, in collaboration with other groups across the university, we have used in silico techniques to identify potential binders to the receptors, tested these compounds in vitro, and confirmed the receptor binding sites of the compounds. By these methods we have been able to identify small molecules which bind either TrkA or TrkB at the point of interaction with their ligands. These are being further developed as candidates for drugs as therapeutics for Alzheimer’s disease and pain.

Teaching

I run and teach Unit 5 of the MSc Molecular Neuroscience course: Neurodegeneration: Symptoms, Molecular Mechanisms and Therapies, and I contribute to the online MSc Stem Cells and Regeneration.

Keywords

  • Alzheimers disease
  • neurodegeneration
  • neurotrophins
  • NGF
  • BDNF

Skills

  • Alzheimers disease
  • Dementia

Processes and functions

  • Memory

Methodologies

  • Protein purification
  • Protein expression
  • Insect cells
  • Bacterial cells
  • Protein characterisation
  • surface plasmon resonance
  • Cell signalling assays
  • In Cell analysis
  • mammalian cell culture

Recent publications

View complete publications list in the University of Bristol publications system

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