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Prof Frances Edwards
Professor of Neurodegeneration
Neuro, Physiology & Pharmacology
Div of Biosciences
- Joined UCL
- 1st Jan 1996
Research summary
The hippocampus in health and disease; Alzheimer's disease: how synaptic transmission goes wrong, long before you can detect cognitive deficits
Memory must involve activity-dependent changes in the network of communication between brain cells. The hippocampus has long been known to be involved in the laying down of memory and much work on this field has concentrated on this area of the brain. Cellular phenomena have been described by which the communication at individual synapses, (the connections between individual neurones), can be strengthened, ('long-term potentiation', LTP) or weakened ('long-term depression', LTD).
In the Edwards lab we are interested in how synapses change and how they react to each other in both health and disease.
1. How synapses work and change in the healthy brain: In healthy mouse and rat brains we use high resolution recording techniques to measure the electrical communication between brain cells in acute and organic brain slices. In addition we can image these cells in detail and observe the changes that occur as connections strengthen and weaken both in response to incoming activity but also in response to changes in neighbouring connections. Understanding such subtle mechanisms is essential to understanding how the healthy network develops and is maintained in terms of general day to day function and the laying down and retrieval of memory. It is also these functions which are likely to go wrong in many neurodegenerative diseases.
2. What goes wrong in Alzheimer's disease: So far there has been no success in treating Alzheimer's disease. Although some drugs temporarily help the symptoms in some people, nothing has been discovered to slow or reverse the progression of the disease. Considering the massive scale of this disease and the devastating effects on the sufferers as well as their families, not to mention the economy, this is an urgent problem to address. Working on the hypothesis that the past failure is because the attempts at treatment come too late, once the brain is already too damaged for repair, we are both studying the earliest changes that occur and the middle period; a long window of opportunity as plaques develop but irreversible damage is yet to occur.
Using mice which express human genes with mutations known to occur in Alzheimer's disease and other disease states, we have observed substantial changes in synaptic transmission at very early stages. By understanding these changes we aim to develop new therapies in an attempt to stop the progression of the disease before substantial irreversible damage has occurred.
The work has now expanded to investigate the genome-wide gene expression in these mice revealing initial changes in synaptic genes followed by a very tight correlation between plaque development and immune genes. Later loss of synaptic genes, presumably indicated to loss of synapses and neurodegeneration is more closely linked to neurofibrillary tangles. Ongoing studies involve the manipulation of the genes of interest to understand which genes influence the susceptibility of the brain to the formation of neurofibrillary tangles and neurodegeneration.
Teaching summary
In 1997 Frances Edwards and Maria Fitzgerald set up the MSc Neuroscience at UCL which Edwards then ran with a series of other colleagues until 2013. This is a highly academic research based degree exposing about 40 students per year to the most recent neuroscience research from across the whole of UCL in the form of research seminars, journal clubs and an extensive research project.
Now relieved of this major administrative and teaching load, Frances Edwards still contributes to the MSc and is teaching on a range of different undergraduate course in Neuroscience as well as contributing to the practical lab experience of undergraduate and graduate students.
Education
- Australian National University
- Doctorate, Doctorat | 1990
- University of Sydney
- Other higher degree, Master of Science | 1984
- University of Sydney
- First Degree, Bachelor of Science (Honours) | 1980
Biography
Dr Frances Edwards graduated in Pharmacology at the University of Sydney, Australia and received her PhD whilst working at the Max-Planck Institute in Germany under the Nobel Prize winner, Prof. Bert Sakmann.
After staying on as a postdoctoral fellow in Sakmann's lab, in 1990 she joined David Colquhoun’s group in Pharmacology at UCL as a Wellcome European Fellow.
After returning to Australia in 1992 Frances held a Queen Elizabeth II Research Fellowship at the University of Sydney from 1993 until 1996.
In 1996 she joined the Department of Physiology at UCL. Until 2010 the focus of the Edwards lab was mechanisms of fast synaptic transmission and the role of dendritic spines in plasticity using electrophysiology and confocal imaging.
In 2010 the research direction largely shifted to research on Alzheimer's disease, studying several transgenic mouse models of human mutations in the amyloid pathway or microtubule-associated protein tau. Recently improved knock in models have been developed and these are now the focus of the lab.
The approaches have expanded to include a range of molecular biology and immunohistochemical techniques and genetics (in collaboration with John Hardy).
Along with synaptic changes the lab is now interested in the role of the immune system in Alzheimer and the interface between amyloid plaques and neurofibrillary tangles as well as developing improved mouse models to address these questions more effectively.