Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/3209244

In Collections

This item can be found in the following collections:

Willacey, C.C.W. (2021)

Developing metabolomics for a systems biology approach to understand Parkinson's disease

Doctoral Thesis
Neurodegenerative diseases, including Parkinson’s disease (PD), are increasing in prevalence due to the aging population. Despite extensive study, these diseases are still not fully understood and the lack of personalised treatment options that can target the cause of the diseases, rather than the symptoms, has led to a greater demand for improved disease understanding, therapies and diagnostic procedures. In this thesis, we use systems biology approaches to construct disease-specific models intended for biomarker discovery, therapeutic treatment strategy identification and drug repurposing in PD. Systems biology is a mathematical field of research that analyses biological systems via construction of a computational model using experimental data. This is achieved by integration of omics data, including genomics, proteomics, transcriptomics and metabolomics. A specific approach used to identify the physico- and biochemical bounds within a biological system is constraint-based...Show moreNeurodegenerative diseases, including Parkinson’s disease (PD), are increasing in prevalence due to the aging population. Despite extensive study, these diseases are still not fully understood and the lack of personalised treatment options that can target the cause of the diseases, rather than the symptoms, has led to a greater demand for improved disease understanding, therapies and diagnostic procedures. In this thesis, we use systems biology approaches to construct disease-specific models intended for biomarker discovery, therapeutic treatment strategy identification and drug repurposing in PD. Systems biology is a mathematical field of research that analyses biological systems via construction of a computational model using experimental data. This is achieved by integration of omics data, including genomics, proteomics, transcriptomics and metabolomics. A specific approach used to identify the physico- and biochemical bounds within a biological system is constraint-based modelling, which requires the input of absolute quantitative metabolomics data. To improve our absolute quantitative coverage of the metabolome, we developed and improved new quantitative metabolomics methods using a targeted mass spectrometry workflow to obtain data intended to be integrated into constraint-based metabolic models for the study of PD.
Show less
Parkinson's disease
Metabolomics
Mitochondria
Systems Biology
Metabolic atlas
Chemical derivatization
Miniaturization
LC-MS/MS
Personalized medicine
Quantitation
All authors
Willacey, C.C.W.
Supervisor
Hankemeier, T.
Co-supervisor
Harms, A.C.; Fleming, R.M.T.
Committee
Irth, H.; Bouwstra, J.A.; Klein, C.; Stelt, M. van der; Knibbe, C.; Bakker, B.M.
Qualification
Doctor (dr.)
Awarding Institution
Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University
Date
2021-09-08
ISBN (print)
9789083171388

Funding

Sponsorship
The research was financially supported by the SysMedPD project, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no. 668738.