Claire Naylor was a student at Somerville, gaining a 1st class degree in Chemistry in 1993 and a D.Phil in Crystallography in 1996. She is now a Royal Society Dorothy Hodgkin Fellow in the Protein Toxins Structure Group at Birkbeck College. She started by explaining that as all the previous lecturers in this series had been Dorothy's students, she felt more like one of Dorothy's grandchildren since her supervisor had been one of Dorothy's students.
Her current research is on pathogenic proteins, particularly those secreted by bacteria, 99.9% of which are completely harmless to humans, and survive for years intheir environemt, but others are toxic, for example, the streptococcus which causes sore throats, in other forms is the MRSA 'Super bug' resistant to most antibiotics. Her current interest is in lethal bacterial toxins including the Clostridium perfringens alpha-toxin, and others associated with this one. This protein is widely distributed being found in human and animal gut and in the soil. One toxin is an entero toxin, a common cause of food poisoning which causes vomiting and diarrhea, but lasts only 48 hours in healthy adults and is rarely toxic. Epsilon toxin causes a nervous disorder in sheep, with a swelling of the brain which proves fatal in 48 hours. Beta toxin is common amongst people who have been existing on a meagre diet and then have a huge meal of more nourishing food. It forms a type of gangrene in the intestines. It was first detected in the victims from concentration camps, but now there is a vaccination against it.
The alpha toxin is associated with the disease 'gas-gangrene' which has been known for a long time. Graphic illustrations were shown of the unpleasant symptoms of gas gangrene. King Richard I is thought to have died from it, when his wound from a crossbow became infected. It has caused sudden death in Belgian bee colonies, 100,000 soldiers died from it during World War I and it caused an epidemic following a tidal wave in 1998 in Papua New Guinea. It is the first major toxin to be shown to be an enzyme, but the exact mechanism of how it destroys other cells is not known. It thrives in wounds where the supply of oxygen is limited. The only known cure is amputation of the affected limb.
Their research group is using several techniques to study the effects of the toxin on mammalian cells taken from the heart and lungs of cows. The alpha toxins surround healthy cells and destroy the protective cell surface membranes. These are made of phosphor lipid bilayers which are attacked by the toxin; it 'slices' off the hydrophilic head groups, leaving the hydrophobic tails within the cell, where they may trigger inflammation and release of calcium ions, which are used in signal transmission with neighbouring cells. The toxin has been crystallised and its structure found so that the conformation of the 'active site' which causes the damage can be studied in the hope of eventually developing a less drastic treatment than amputation for wounds infected with 'gas gangrene'. An additional problem is that these alpha toxins suppress the immune response but it is not known how they do this, so further studies are needed.
Margaret Adams thanked the lecturer for giving us this fascinating and well illustrated lecture despite suffering from a sore throat. We then adjourned for a reception in the mainhall of the University Museum with its Victorian architecture and dinosaur skeletons.
Kate Crennell
March 2003