Identification of genetic modifiers of prion replication and neurotoxicity
Supervisor: Dr Raymond Bujdoso
2015 – present: PhD in Bioscience (BBSRC DTP), Department of Veterinary Medicine, University of Cambridge, UK
2014 – 2015: MRes in Bioscience (BBSRC DTP), Department of Veterinary Medicine and Institute of Metabolic Science (MRL), University of Cambridge, UK
2012 – 2014: MSc in Animal Biotechnologies, Mendel University in Brno, Czech Republic
2009 – 2012: BSc in Molecular Biology and Genetics, Masaryk University, Czech Republic
My research interests are focused on neurodegenerative diseases, in particular those that arise through the mechanism of protein mis-folding. These neurodegenerative disorders include prion diseases, which affect humans and animals, and human-specific diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and motor neurone disease. These conditions all arise through the mis-folding of a disease-specific protein that accumulates in the brain of affected individual and that causes damage to neurons. Prion diseases have emerged as an important model for other protein mis-folding diseases since they show prion-like phenomena, such as cell-to-cell spread of mis-folded protein.
Protein mis-folding neurodegenerative diseases are an important issue for human and animal health. Prion diseases are unique amongst protein mis-folding neurodegenerative diseases because they are transmissible between individuals of the same or different species and are therefore a threat to human and animal food safety. In addition, the increasing number of aged people with their increased predisposition to neurodegeneration has led to an increase in the number of people with conditions such as AD and PD. For these reasons research on protein mis-folding neurodegenerative diseases is highly important.
My aim is to contribute towards addressing some of the unanswered questions associated with protein mis-folding neurodegenerative diseases. For example, it is important to provide an understanding of the mechanism of neurotoxicity induced by protein mis-folding. This knowledge will help provide a basis for the design of effective strategies to deal with these conditions. The study of protein mis-folding neurodegenerative diseases in their natural hosts is difficult and research on these conditions increasingly relies upon the use of animal models.
My PhD project will test the hypothesis that the PrP transgenic Drosophila melanogaster can act as a model for inherited and transmissible prion diseases. Modelling prion diseases in a genetically well-defined tractable invertebrate host will provide a novel approach to identify the genes and cellular mechanisms that affect the way mis-folded and aggregated prion protein causes damage to neurons. Understanding this process will be critical for the design of better diagnostic tests for these conditions and to develop new medicines that can block key steps in the disease process. The information will be directly relevant to prion diseases per se but will also be useful to other human brain diseases that show prion-like phenomenon. Furthermore, the use of the invertebrate host Drosophila melanogaster for these studies will also contribute to the principals of the 3Rs approach to reducing the use of sentient animals in research.
Dr Alana Thackray – Department of Veterinary Medicine, University of Cambridge
Dr Walker Jackson - German Center for Neurodegenerative Diseases (DZNE), Bonn
Prof Dr Ina Vorberg - German Center for Neurodegenerative Diseases (DZNE), Bonn
Dr Matthias Landgraf – Department of Zoology, University of Cambridge
Dr Giles Yeo – Institute of Metabolic Science, Cambridge Biomedical Campus, Addenbrooke’s Hospital, University of Cambridge
Dr Brian Lam - Institute of Metabolic Science, Cambridge Biomedical Campus, Addenbrooke’s Hospital, University of Cambridge