Researchers in the Biochemistry Department at University College Cork are involved in an EU study into how BSE and its human form, Creutzfeldt-Jakob Disease (CJD), can cause illness. It is a complex study that examines in tremendous detail what goes on inside the human cell.
Dr Mary McCaffrey is Cork's group leader for the project at the Cell and Molecular Biology Laboratory in the Biochemistry Department. The research initiative involves partners in Britain, Italy and France and is one of 23 studies into the transmissible spongiform encephalopathies being funded by the European Commission.
"Some years ago the EU recognised it as a problem and decided the Union should invest in basic research," Dr McCaffrey explained.
"The reason that we came to it is that I had been working on the fundamental processes of how materials move into and out of cells," she said.
It is "a very complex procedure" which is fundamental to cell survival.
Until BSE arose CJD in humans was a relatively rare disease. Spontaneous CJD occurs in about one in a million people and the disease can also be inherited. Transmissible forms are known in humans but only in extreme circumstances, for example in the case of cannibalism in Papua New Guinea and known there as Kuru.
The situation changed when BSE arrived, bringing with it studies to examine whether humans might be at risk from the disease. A new form of the human disease was identified, variant CJD (vCJD) and more than 85 cases have been identified in the UK so far. Studies have established a direct link between the two diseases.
Dr McCaffrey is an expert in the range of proteins involved in bringing materials across the cell membrane. In particular, this includes a group known as the Rab Small GTPases. These proteins "control essential events" inside the cell, she said, including the transport of the abnormal prion protein that causes vCJD.
Materials reaching the cell wall sometimes simply move across it and pass through while others are broken down inside. Rab controls these events, acting like a "sorting station", Dr McCaffrey explained.
The normal prion is found in all tissue types but is most plentiful in brain tissues. Research studies have shown that if an abnormal prion is introduced it can change normal proteins, transforming them into the abnormal form. The working theory on how normal prions are transformed involves contact with aberrant prions in a low pH environment, the same environment found inside the cell in what are known as endosomal organelles. These small bodies inside the cell are central to the transport process, Dr McCaffrey explained. Her team is studying this on a number of levels using cultured human tissues and examining them for the presence of the normal prion. The assumption is that the abnormal form will behave like the normal form and there is research evidence to support this view.
Dr McCaffrey has been searching for associations between the Rab transport proteins and the prions and early data has provided this association. A technique known as immunoprecipitation uses antibodies that target the prion and this showed Rab and prions in the same organelle.