Universiteit Leiden

nl en

Research project

Enabling volume-restricted metabolomics using next-generation microscale analytical tools

Development of micro-scale analytical tools to be used to address relevant biomedical questions in the field of neuroscience, and other application areas intrinsically dealing with small sample amounts.

Duration
2018  -   2023
Contact
Rawi Ramautar
Funding
NWO Vidi NWO Vidi
Partners

Dr. Julie Schappler and Dr. Serge Rudaz, Biomedical and Metabolomics Analysis, Université de Genève (UNIGE).

Prof. dr. Yvan Vander Heyden and prof. dr. Debby Mangelings, Department of Analytical Chemistry, Applied Chemometrics and Molecular Modelling, Vrije Universiteit Brussel.

Research

The analytical toolbox used in present-day metabolomics ,and bioanalysis in general, encounters difficulties for the analysis of limited amounts of biological samples. As a result, a significant number of crucial biomedical and clinical questions cannot be addressed by the current metabolomics approach. In this context,  research in my group is focused on the design of microscale analytical separation techniques and workflows for highly sensitive metabolic profiling of size-limited biological samples. Also, attention will be paid to the development of microscale analytical tools for the enantioselective characterization of (endogenous) metabolites, thereby aiming to provide a unique and versatile tool in metabolomics.
On of the analytical technologies that will be considered for these purposes is capillary electrophoresis (CE)-mass spectrometry (MS). CE is a microscale analytical technique providing highly efficient separations for (highly) polar and charged compounds, while requiring only minute amounts of sample. CE can be coupled to MS via various interfacing designs and the state-of-the-art in this area will be explored in order to allow hyphenation of CE and electrospray ionization (ESI)-MS under optimal conditions, i.e. where both the separation efficiency of CE and the ionization efficiency of ESI-MS are maximal. Tailor-made sample preparation strategies for limited amounts of biological samples will be developed. Another exciting field that is virtually unexplored in metabolomics is chirality. Therefore, a blend of chiral selectors will be evaluated to obtain a chiral perspective on the metabolic composition of volume-restricted samples by the CE-MS analytical technology.
The developed micro-scale analytical tools will be used to address relevant biomedical questions in the field of neuroscience, and other application areas intrinsically dealing with small sample amounts. The role of D-amino acids, a novel class of neuromodulators, and other chiral metabolites will be studied for various diseases. Overall, the analytical technologies and workflows developed in my group should enable in particular those metabolomics studies that have so far been lacking. As such, research performed at the Biomedical Microscale Analytics group within the division of Systems Biomedicine and Pharmacology of the LACDR will provide analytical strategies for a deeper understanding of biological processes in sample-limited cases.

Key publications

1.      Ramautar R, Berger R, van der Greef J, Hankemeier T. Human metabolomics: Strategies to understand biology. Curr Opin Chem Biol 2013;17:841-6.
2.      Ramautar R, Busnel JM, Deelder AM, Mayboroda OA. Enhancing the coverage of the urinary metabolome by sheathless capillary electrophoresis-mass spectrometry. Anal Chem 2012;84:885-92.
3.      Gulersonmez MC, Lock S, Hankemeier T, Ramautar R. Sheathless capillary electrophoresis-mass spectrometry for anionic metabolic profiling. Electrophoresis 2016;37:1007-14.
4.      Zhang W, Hankemeier T, Ramautar R. Next-generation capillary electrophoresis-mass spectrometry approaches in metabolomics. Curr Opin Biotechnol 2017;43:1-7.
5.      Zhang W, Gulersonmez MC, Hankemeier T, Ramautar R. Sheathless capillary electrophoresis-mass spectrometry for metabolic profiling of biological samples. Jove-J Vis Exp 2016.