Jon Wadsworth
Jonathan Wadsworth
Molecular and Phenotypic Analysis
of Prion Strains

Jonathan studied Biochemistry at Imperial College London and was awarded a PhD in 1990 for work investigating the neuro-paralytic activities of botulinum neurotoxins. His early post-doctoral work at the Royal Postgraduate Medical School in London focused upon the pharmacology of neurotoxins from insect, snake and scorpion venoms.

In 1997 he joined Professor John Collinge at St. Mary’s Hospital London to work on prion diseases and moved with Professor Collinge to UCL in 2001. Jonathan is currently a Programme Leader within the MRC Prion Unit directed by Professor Collinge and Reader in Prion Diseases within the Department of Neurodegenerative Disease at the UCL Institute of Neurology. Jonathan’s main research focus is to define the molecular composition and three-dimensional structure of human prions and he works closely with staff in the National Prion Clinic to assist with the analysis of patient diagnostic samples.

Prions, the infectious agents causing BSE in cows and CJD in humans are unique in medical research. Unlike all other infectious agents (bacteria and viruses) the infectious particle does not contain genetic information (genes) but instead consists of a protein (called PrPSc). Although prions do not carry genetic material they come in several different forms, called prion strains that cause different forms of the disease. Our research aims to understand the fundamental biology of what makes prion strains different from one another and why some are able to cross from animals to humans to cause disease. Our research focuses on isolating infectious prion particles from diseased tissue and using sophisticated equipment to study their chemical makeup and three-dimensional structure. Through these studies we aim to provide a detailed description of the protein (PrPSc) associated with each prion strain and pinpoint exactly what differences are responsible for a particular form of disease.

For some studies we use model prion strains from mice that can be detected in isolated cells allowing us to make much faster progress than has been previously possible. In other studies we use genetically altered mice (transgenic mice) to understand which animal prion strains may pose a risk to humans and to see what these diseases may look like should people become infected. These studies have confirmed that variant CJD is caused by the same prion strain that causes BSE in cows and have established that a person’s genetic makeup may influence the type of prion disease they will develop if infected with BSE prions. Because of the very long time periods possible between infection and the appearance of symptoms the number of people with BSE infection is unknown. This has raised fears that infected people who have no signs of the disease might pass it on to others by surgery, blood transfusion and other medical routes. We have pioneered laboratory tests to rapidly detect variant CJD and other forms of disease caused by BSE infection should they occur. Our findings have been used throughout the world to help accurately diagnose human prion diseases and have assisted the World Health Organisation to develop measures to limit the spread of these diseases from one person to another by medical procedures. Recently using new methods that we developed we were able to obtain the first three-dimensional images of isolated prions and we are now concentrating on using these techniques to find differences between prion strains.