![]() However, existing circRNA investigations in PD are very limited. It is likely that circRNAs play an important role in Parkinson’s disease (PD), possibly correlating to disease pathoetiology or potentially acting as biomarkers which predict PD or the transition to Parkinson’s disease dementia (PDD). Is circular RNA a biomarker of Parkinson’s Disease?Ĭo-investigators: Dr Mike Jackson & Dr Mauro Santibanez-KorefĬircular RNAs (circRNAs) are rapidly gaining attention in studies of human disease due to their possible use as clinical biomarkers and their potential to affect gene expression. This project utilises samples and data from the Parkinson’s Progression Markers Initiative (PPMI). This project utilises a broad clinical spectrum including PD, AD, dementia with Lewy bodies and Multiple Sclerosis, where we will assess the function and integrity of ccf-mtDNA within the CSF to better understand how it contributes to the development and progression of neurodegeneration. Ccf-mtDNA copy number has been found to be depleted in both Parkinson’s disease (PD) and Alzheimer’s disease (AD) cerebrospinal fluid (CSF), raising the hypothesis that it could be used as a biomarker for neurodegenerative disease. MtDNA has been found to exist cell-free within human body fluids, coined circulating cell-free mtDNA (ccf-mtDNA). Post-Doctoral Scientist: Dr Hannah Lowes. The role of cell-free mtDNA in neurodegenerative disease. I will explore this by investigating the effect of inherited mtDNA variation on cellular transcriptomics in different brain regions from PD patients, comparing RNA abundance to asymptomatic controls. Previous research during my PDUK senior fellowship (F-1202) has shown that particular mtDNA variants (haplogroups) can protect from or increase the risk of developing PD. The aim of this research project is to investigate the role of mitochondrial DNA (mtDNA) variation in neurodegenerative diseases. Investigating the role of inherited and acquired mitochondrial DNA variation in neurodegeneration. This cross-disciplinary PhD will utilise expertise from the Newcastle Fertility Centre, Institute of Genetic Medicine and Wellcome Centre for Mitochondrial Research. ![]() Jordan's PhD will investigate the effects of several key components of mitochondrial function, including mitophagy, mitochondrial DNA variation and transcriptomics on the safety of future MRT experiments. Among the possible explanations are (i) Preferential replication of mitochondrial genomes located in the peri-nuclear region (ii) Replicative advantage associated with certain mitochondrial genomes (iii) A founder cell effect due to unequal distribution of variant mitochondrial genomes during the early embryonic divisions. The principle aim of this project is to improve our understanding of the roles that mitochondrial function and mitochondrial DNA play in developing embryos. Mitochondrial donation offers the potential to prevent transmission of mtDNA disease. Our work indicates that expansion of mtDNA carried over during pronuclear transfer (PNT) is unpredictable, with highly similar sequences (effectively clones) reverting back to “maternal” type in ~20% of embryonic stem cell lines derived from PNT blastocysts. Investigating mitochondrial homeostasis during early development Assessing the role that inherited mtDNA variation plays is shaping cellular transcriptomics in disease and development.Assessing the effect of combinations of mtDNA/nDNA variants in the population on disease.Directly assessing the role that inherited mtDNA variation plays in these contexts.My current research is aimed at improving our understanding of this interaction in human disease and development by: Mitochondrial function is dependent on the continued cooperation of both the mitochondrial and nuclear genomes (mtDNA/nDNA communication), raising the possibility that the associations between inherited mtDNA variation and disease are a manifestation of a break in the tightly controlled communication that exists between mtDNA and nDNA. However, we know little of how this inherited mtDNA variation exerts its effect in these complex diseases. My research to date has solidified the role of inherited mtDNA variation in several complex traits. Mitochondrial DNA (mtDNA) is highly variable, with individuals easily classified by characteristic clades of inherited variation.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |