I was educated at St Paul's Girls' School in Hammersmith, where I was a junior and senior Foundation Scholar. Afterwards, I studied for a BSc in physics, then worked for an MSc in Biophysics - being awarded one of the only two studentships then available in that subject - and finally proceeded to a PhD in Biophysics - all London University degrees.

I then moved to Cambridge, working in the University Department of Radiotherapeutics. I held a Beit Memorial Fellowship for Medical Research and the Wheldale-Onslow Memorial Fellowship (and Praelectorship) at Newnham College. One paper I published in Cambridge became a "citation classic". My next move was to Manchester where I worked initially in the Paterson Laboratories and subsequently in the Department of Optometry and Neuroscience, UMIST.

My research topics have been diverse: iron-binding in plasma; effects of ionising radiation on natural and synthetic macromolecules; chromatin structure (I was the first to use polylysine and a nuclease to investigate this); effects of irradiation on chromatin; carcinogens and chromatin; viruses and neurological disease. More recently I have been studying Alzheimer's disease, in particular defective DNA repair, aluminium, and in most detail, the role of viruses acting with a genetic factor in dementia. For the virus work (see Research) I won an Investigator award from the Lancet, a Wellcome Trust Innovative award, two Olympus Foundation awards, an Alzheimer's Research Forum award and a Manchester City Council award. Our other research topic, which stems from the Alzheimer's disease work, is on the role of the same genetic factor in determining outcome of infection by pathogens.

I am married; my husband is a scientist, and we have non-identical twin daughters, both scientists. I love music (am an ex-pianist and violinist) - particularly "early" music and that of Bach - followed by Mozart, Beethoven and Brahms - reading, travelling (or rather, arriving), and swimming and snorkeling in warm seas.

Cell and Molecular Biology of Alzheimer's Disease and Neurovirology

Alzheimer’s disease (AD) affects 18 million people worldwide, and the numbers will rise with increasing longevity. Currently, neither prevention nor treatment is available. Indeed, the causes of AD are unknown, as are those of the main abnormal brain features, amyloid plaques and neurofibrillary tangles, which are thought to be involved in disease development. Our results indicate that a virus plays a major role in AD. This points to antiviral treatment to slow deterioration in those afflicted, and vaccination to prevent AD.

Several common viruses can cause serious neurological disease years after initial infection. In AD, herpes simplex virus type 1 (HSV1) was originally suggested as a candidate agent as it is ubiquitous, and in the acute brain infection, herpes simplex encephalitis (HSE), it affects the same brain regions as those most damaged in AD. However, it was uncertain whether HSV1 was present in the brain in normal circumstances. We discovered by using polymerase chain reaction that HSV1 DNA indeed resides in brain of a high proportion of AD patients and elderly normals, and using an immunological technique we substantiated viral presence and showed that it is active there.

HSV1 DNA presence in elderly normal as well as AD patients’ brains does not preclude a viral role in AD. Microbial infection can be asymptomatic, the outcome probably depending on host genetic factors. In fact we found a strong association between HSV1 presence in brain and carriage of the type 4 allele (APOE-e4) of the gene encoding apolipoprotein E, a known susceptibility factor for AD. The combination accounted for 60% of our cases. Also, a high proportion of sufferers from cold sores, which are caused usually by HSV1, were APOE-e4 carriers. We therefore suggested that HSV1 and APOE-e4 together are particularly harmful in the nervous system, and that as in the peripheral nervous system, HSV1 reactivates from latency in brain during stress, immunosuppression, etc, causing localised damage which is greater in APOE-e4 carriers, leading to AD.

HSV1 and the protein, apoE, might compete for cell entry, as both bind to certain surface molecules, and the extent of competition could determine extent of damage. In fact we found that APOE governs outcome of infection by several other microbes that use the surface molecules.

We then discovered direct links between HSV1 and the abnormalities of AD brain: HSV1 infection of cultured cells leads to deposition of β-amyloid (Aβ), the main component of plaques, and infection of mice results in Aβ deposition in brain. Also, in cultured cells, HSV1 causes AD-like phosphorylated tau (P-tau), the main component of tangles. Further, on investigating the location of HSV1 in AD brain, we found, excitingly, that most of the viral DNA is associated with plaques and almost all plaques contain HSV1 DNA. Association does not prove causality, but together with the HSV1-induced increase in Aβ, the data strongly suggest that HSV1 is responsible for production of amyloid and its toxic products and thus for plaque formation in AD brains.

Recently we investigated the effects of an antiviral agent on the HSV1-induced production of Aβ and P-tau. Anti-HSV1 antiviral agents such as acyclovir (ACV) would prevent HSV1-induced damage that depends on viral DNA synthesis, and also other HSV1 damage by decreasing viral spread. We found that ACV greatly reduces Aβ and P-tau, thus substantiating its use for AD treatment, especially as ACV, unlike other AD treatments, would not target normal cell products.

Alzheimer’s disease (AD) is a major brain disease, afflicting about 18 million elderly people worldwide. This figure will rise with increasing longevity, so there is an urgent need for effective treatment. The brains of AD sufferers contain many abnormal deposits called plaques and tangles, which are thought to play a crucial role in the disease. However, the causes of their formation and of the disease itself are unknown. We have been investigating whether a common virus has a role in AD. We found that many elderly people harbour this virus within their brain but only those who have a specific genetic factor are at risk of developing AD. Subsequently we discovered that the viral DNA is located specifically within plaques; also, infection with this virus causes production of the main components of plaques and tangles (called beta-amyloid and abnormal tau), indicating that the virus might be a cause of these abnormal deposits. Our recent experiments with antiviral agents indicate that they might be an effective treatment to slow AD progression in that they decrease the levels of beta-amyloid and abnormal tau which the virus induces. Also, the future possibility exists of prevention of the disease by vaccination against the virus.