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Applied Metabolomics

The activity of the Applied Metabolomics Research Laboratory can be divided into two main lines of work.

Development and application of metabolomic strategies for detecting biomarkers of different disease states.

The main aim of this research is to develop an analytical method suitable for detecting changes produced in the metabolic routes of interest and applying this method to various healthcare areas. To do this, the lab has developed both targeted metabolomic and non-targeted metabolomic methods. These methods have been applied in different fields. In the case of targeted metabolomics, alterations in steroidogenesis are being studied in several states including:  

• Acute intermittent porphyria. There is an imbalance in adrenal steroid production and there is a positive correlation between this imbalance and the severity of the disease. This study is part of a project financed by the ISCIII in collaboration with Hospital Clinic, in Barcelona.  
• Night-time exposure to light. It has been observed that night shift workers have increased progestogen levels. This hormonal imbalance may be related to the possible link between night work and hormone-dependent cancers, as recognised by the WHO. This study is part of the Hormonit project and is undertaken in collaboration with ISGlobal.

In addition, within this field the lab collaborates on the prenatal diagnosis of diseases related to steroidogenesis (in collaboration with the University of Birmingham), and on determining the effect of steroid hormone imbalance on foetal growth retardation (in collaboration with IDIBAPS).

Targeted metabolomic strategies related to neurotransmitter determination are being applied to fields such as:

• Acute intermittent porphyria. An imbalance in tryptophan metabolism has been observed, increasing kinurenin production. This ongoing study is part of a project financed by the ISCIII in collaboration with Hospital Clinic in Barcelona.
• Predicting the effect of new psychoactive substances. This involves evaluating the changes produced in the metabolome after administrating psychoactive substances. Based on these changes the substances are classified into different groups. This project is part of the PREDICT project financed by the European Commission.
• Effect of maternal separation on the brain concentration of neurotransmitters. Changes in concentrations of neurotransmitters in the brain have been seen following maternal separation. This project is undertaken in collaboration with the Neurobiology of Behaviour research group at the UPF.

In addition, the number of metabolic pathways studied in targeted metabolomic strategies is being expanded. Specifically, methods for quantifying Krebs cycle metabolites and glycine-conjugated acids are being optimised. These methods will be applied to evaluate energy deficiency and the role of the glycine modulator in various fields of application.

Finally, within the development of non-targeted metabolomics, strategies have been developed to detect phase II metabolites. Contacts have been established to explore the possibilities of open metabolomics for detecting markers involved in various fields, such as foetal alcohol syndrome (in collaboration with the FIMIM Childhood and Environment Research Group), and specific metabolic pathways for Plasmodium (in collaboration with the Jaume I University and the IBEC nanomalaria unit)

Elucidation of alternative forms of conjugation and evaluation of their clinical relevance.

Within this field of research several progestogens conjugated with cysteine have been discovered, and their gonadal and/or adrenal origin has been established. In addition, the urinary excretion of these compounds has been shown to follow a marked circadian rhythm. Both the changes in the amount of excreted metabolites and the alterations observed in the circadian rhythm phase are being evaluated.

This study is part of the Hormonit project and is undertaken in collaboration with ISGlobal. In addition, a metabolomics method has been developed for detecting bis-sulfate metabolites. This method is being used to detect diagnostic markers of diseases related to steroidogenesis (in collaboration with the University of Birmingham).

Furthermore, the presence of succinic acid conjugates has been discovered following the administration of psychoactive substances, such as mephedrone. The origin of this is being studied in more detail, and the lab aims to evaluate the clinical relevance of this type of conjugate.