Professor Parmjit Jat, Lecturer Melissa L.D. Rayner, and Simon Mead, PhD

Grant Title: Elucidating the factors required for propagating human CJD prions

Location: MRC Prion at UCL, Institute of Prion Diseases, London

Grant Year: 2023

Prion diseases are associated with the build-up in the brain of an abnormal or ‘rogue’ form of a naturally occurring protein, known as the prion protein. The rogue protein results from a change in shape of the normal prion protein. Our project is aimed at identifying the additional factors that are required for human prions to grow in cells in the laboratory. Developing cells that can grow human prions has been an important, yet elusive goal of the prion field for several decades. Cells capable of growing mouse and other animal prions, thereby enabling their accurate measurement has enabled a number of important advances in understanding prion biology. Efforts to develop cells that can propagate human prions have been largely unsuccessful due to the lack of understanding of the factors required for them to grow. We have recently used cell engineering to develop cells which are susceptible to very low levels of human prions and can reproducibly and stably grow human Creutzfeldt-Jakob disease prions in the laboratory. We will use these cells to identify the changes at the molecular level that lead to the increased susceptibility and ability to grow prions.

About the Researchers:

Professor Parmjit Jat
MRC Prion at UCL, Institute of Prion Diseases, London

In 2003, Parmjit was appointed a Professor of Molecular Cellular Biology in the Department of Neurodegenerative Diseases at the UCL Institute of Neurology. Subsequently, in 2013, he was seconded to the MRC Prion Unit at UCL to lead the Cell Biology Programme tasked with investigating the central role of the prion protein in functions related to the development of prion disease. The programme has achieved ground breaking success in developing cells that can stably propagate sporadic Creutzfeldt-Jakob disease prions whilst also developing a multi-parametric imaging assay for the prion induced neurotoxic species to enable its purification and characterisation.

Recently, in 2021, Parmjit was appointed a Commissioner for the Commonwealth Scholarship Commission (CSC) in the UK. The CSC provides the main UK government scholarship scheme led by international development objectives. It is an executive non-departmental public body, sponsored by the Foreign, Commonwealth & Development Office.

Lecturer Melissa L.D. Rayner
UCL School of Pharmacy, London

In 2019, Melissa joined the UCL Institute of Prion Diseases as a postdoctoral research fellow. Her project was to develop an assay for reproducibly quantifying infectious human prions. Melissa has developed cells that can reproducibly and stably propagate human variant CJD prions. These cells will now be used to identify the cellular factors that are required in addition to the human prion protein for propagation of these infectious prions.

Recently, in 2022, Melissa was appointed as a Lecturer of Pharmacology and Principal Investigator at the UCL School of Pharmacy where she is leading research in the development of drug and cell-based therapies to promote nerve regeneration following damage.

Simon Mead, PhD
In 2007, Simon was appointed as a Consultant Neurologist and Clinical Lead of the National Prion Clinic based at the National Hospital for Neurology and Neurosurgery, UCLH.

Simon leads the Human Genetics, Bioinformatics and Epigenetics programme and is also co-lead of the Clinical programme. His research interest include treatment and designs for clinical trials in CJD and other human prion disease, the discovery of biomarkers, genetic and epigenetic factors that cause or modify prion disease. He was made a Professor at UCL in 2014, NIHR Senior Investigator in 2018 and Deputy Director of the MRC Prion at UCL in 2018.

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