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MRC Prion Unit
From fundamental research to prevention and cure
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MRC Research Groups

Human molecular genetics of prion and related dementias

Simon Mead

Prof. Simon Mead

The MRC Prion Unit Human Genetics Group investigates why some people, but not others, get prion diseases such as Creutzfeldt-Jakob disease (CJD). We know that variant CJD (vCJD) was caused by human transmission of BSE (bovine spongiform encephalopathy or mad cow disease), a prion disease of cattle. Other people develop a prion disease spontaneously as they get older (called sporadic CJD) while others are accidentally infected with prions as a result of medical or surgical procedures (since prions stick to metal instruments, are very resistant to sterilisation and can also be passed in blood transfusions). Read more.

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Transgenic modelling of human prion diseases, intermammalian transmission barriers and assessment of candidate therapeutics

Emmanuel Asante

Dr. Emmanuel Asante

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. Dr Emmanuel Asante and his team have developed a key series of animal models of human prion disease. This involves introducing various forms of the human prion protein gene into mice so that they produce human PrP. This includes both the M and the V form, and 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 (known as type 4) which causes variant CJD (vCJD). Read more.

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Cellular mechanisms of prion propagation

Peter Klohn photo

Dr. Peter-Christian Klöhn

Prions, the infectious agents that cause the lethal brain disease CJD in humans infect a range of different cells in the body. In contrast to other infectious diseases, like viral or bacterial diseases, prions are not recognised as rogue proteins by the immune system and the hosts remain symptom-free for a long period of time. During this phase prions rapidly multiply in lymphoid organs, like the spleen, lymph nodes or tonsils and finally reach the brain where they cause a fatal and progressive loss of neurons. Read more.

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Molecular and phenotypic analysis of prion strains

Jon Wadsworth photo

Dr. Jonathan Wadsworth

We are all familiar with the idea that infectious agents such as bacteria and viruses come in different types or “strains”. It is usually easy in the laboratory to identify the strain causing an outbreak, as each strain will have differences in its genetic material. Take the example of an outbreak of food poisoning. Public health doctors can isolate the germ and strain type it and then try to identify the common source from which people became infected. Although prions do not carry genetic material, they also come in several different forms - again known as strains. Read more.

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Structural studies of prion proteins and their ligand interactions


A major programme in the Unit focuses on the central problem in understanding prions; what is the change in shape that distinguishes normal prion protein, PrPC, from its rogue form, PrPSc, and how does it come about? The team works mainly with the human prion protein itself - which is synthetically produced in the Unit in large quantities (using genetically engineered bacteria) in a specially-designed laboratory. A range of sophisticated equipment is used to study the structure, folding and dynamics of prion protein both in isolation and also with likely binding partners, in order to understand how it changes its shapeRead more.

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Prion kinetics, toxicity and synthesis and its wider relevance

Prof. John Collinge

Prions are lethal pathogens of mammals which occur in multiple biological strains, and yet appear devoid of nucleic acid and composed of aggregated conformational isomers of a host-encoded glycoprotein. Their unique biology, allied with the risks to public health posed by prion zoonoses such as BSE, has focused much attention on understanding the molecular basis of prion propagation and pathogenesis. However, it is clear that the underlying molecular mechanisms, involving aggregation of a misfolded host protein, are of much wider significance and, indeed, analogous protein-based inheritance mechanisms are recognised in yeast and fungi. Read more.

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Molecular diagnostic strategies in prion disease

G.Jackson

Dr. Graham Jackson

The majority of the UK population and a lesser proportion of continental European and the rest of the world have been exposed to mad cow disease or BSE contaminated foods and this has resulted in the new human disease variant CJD (vCJD). Although the number of patients remains small, the number of people infected but without any signs of illness is unknown and could be very large. The time from being infected to showing signs of the disease can be prolonged for up to 50 years. During this period infected individuals are themselves infectious and there is a risk of spreading the disease through the contamination of medical and dental instruments; the use of contaminated blood for transfusion and the transplantation of infected organs such as kidneys. Read more.

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Clinical research studies in the UK

Prof. John Collinge and Dr. Simon Mead

The principal aims of the clinical research programme are to facilitate the translational agenda of the Unit - the development of early diagnostics and effective therapeutics for human prion infection. While the majority of the UK population will have been exposed to BSE prions, the number of clinical cases has thankfully been modest to date. However, the extent of clinically silent infection remains unclear and secondary transmission of vCJD is now a reality. Read more.

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Kuru field studies in Papua New Guinea

Michael Alpers

Prof. John Collinge and Prof. Michael Alpers

The Unit, in collaboration with our colleagues at the Papua New Guinea Institute of Medical Research, has been studying all patients with kuru. Although cannibalism stopped in the late 1950's, a few individuals, who were infected as children, are still developing the disease. Studying these individuals can give us an estimate of what the longest incubation periods can be in humans and also genetic studies may tell us why these individuals have such long incubation periods (some over 50 years). We have also studied older individuals who we know were exposed to kuru, but who have remained healthy. Again, these studies are casting light on what provides resistance to developing disease which may again be very helpful to understanding similar factors in variant CJD. Read more.

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Bioinformatics

Holger Hummerich photo

Dr. Holger Hummerich

The Human Genome Project, which set out to identify all human genes and was completed in 2003, generated a vast amount of data of different types such as sequence, protein structure information or information stored in the literature. Additionally, new techniques were developed to examine the emerging data. Examples are microarray experiments (where thousands of miniscule spots of DNA are made visible according to their abundance at a certainsnapshot in the cell) and genome wide association studies (examination of genetic variation across an entire genome). Read more.

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MRC Prion News