Emmanuel Asante
Emmanuel A Asante
Transgenic Modelling of Human Prion Susceptibility

Emmanuel obtained his BSc (Hons) degree from the University of Ghana and went on to study population and biochemical genetics of lipid metabolism at the Institute of Animal Genetics at the University of Edinburgh, and was awarded a PhD in 1988. He then took up molecular genetics and transgenic animal modelling for his postdoctoral work at the Roslin Institute, learning from the team that generated Dolly, the first cloned sheep.

Emmanuel has successfully applied his expertise in transgenic modelling of prion diseases and is currently the Head of Transgenics within the MRC Prion Unit directed by Professor Collinge. Emmanuel and his team have published many seminal papers based on transgenic modelling, providing one of the early confirmatory experimental data that vCJD derives from BSE infection, and most recently the successful modelling of a single amino acid variant that provided absolute protection against kuru infection in the Fore speaking people of Papua New Guinea.

While the Unit is working to find alternatives to the use of laboratory animals in our research, at this time some crucial work can only be done in mice. One key area of this research is to understand the so-called species barrier that limits the ability of prions from one species of animal to infect another. The most important of these barriers for us to study is that between cows and humans, and to this end we have generated special mice (known as transgenic mice) in which we have inserted a human prion protein gene in order to estimate how large this barrier may be and to begin to understand how the barrier works.

We have developed a key series of animal models of human prion disease, involving the introduction of various forms of the human prion protein gene into mice, including both the M and the V forms. Such mice are very sensitive to infection with CJD prions and have allowed us to study the various strains of human prions, including notably the strain which causes variant CJD.

These studies have formed an important part of the evidence showing that variant CJD is the human counterpart of BSE and we have been able to reproduce the characteristic features of variant CJD seen down the microscope (known as florid plaques) in these mice. This model then allows us to test possible treatments for the
human disease. Emmanuel is also modelling various genetic mutations that are seen in patients with inherited forms of prion disease (also known as familial CJD and GSS). By introducing the mutant human gene in mice, we can study how it causes disease in those families with a faulty prion protein gene.

In a study published in Nature in June 2015 that attracted worldwide media interest, Emmanuel and his team have
successfully demonstrated in transgenic mice that a novel genetic change at amino acid position 127 where the normally conserved glycine (G) is replaced by valine (V) provided absolute protection against kuru infection to carriers of a single copy of the variant 127V, and that the protection followed an entirely different mechanism from the well-established codon 129 protective effect.