Associate Professor Gilbert Alexis has returned from two months stay in Nantes supported by the WRH Faculty Research Abroad Program. This is a report on the activities and results of his stay.

Prof. Gilbert in the middle

 

Destination Institution	CEISAM Laboratory, University of Nantes
City and Country	Nantes, France
Host Researcher	Illa TEA, Associate Professor
Travel Period	2024/01/15 – 2024/03/15 (60 Days)
Project Title	(Japanese) 安定同位体分析による医療診断
	(English) Position-specific isotope analysis as a medical diagnosis tool

The variation of stable isotope ratios (²H/¹H. ¹³C/¹²C, ¹⁵N/¹⁴N) is an invaluable source of information on the origin and history of a molecule. As such, stable isotopes could be an interesting tool to (i) understand changes in metabolic activities in cancer vs healthy cells and (ii) diagnose cancers for which current diagnoses are insufficient.

While differences in isotope ratios in cancer and healthy cells have been reported (Tea et al. 2016), the causes underlying these differences remain to be elucidated. This project aims at advancing both of these aspects by employing new methods, namely, position-specific isotope analysis, to improve our capability to diagnose and understand changes in metabolisms due to cancer proliferation.

In this project, we propose to develop methods for the precise measurement of ¹⁵N and ¹³C PSIA to molecules, amino acids and organic acids in particular, which isotope composition can record metabolic changes and thus have the potential to improve our understanding and diagnostic capability.

The collaboration between Dr. Illa Tea and Dr. Alexis Gilbert has started in January 2024. The goal was to implement the device used in Tokyo for ¹³C-PSIA to the University of Nantes in order to measure ¹⁵N-PSIA some metabolites. We could implement the method for ¹³C-position-specific isotope analysis, and successfully measured simple molecules such as ethanol and pentane. Implementing the device for ¹⁵N analysis has been slightly delayed due to the constraints below:

• The parts required to implement the system in Nantes took some time to be delivered
• After a thorough literature review, it appears that some, if not all, of the analytes that we targeted (arginine, ornithine, citrulline) may not produce enough fragments for a complete ¹⁵N-PSIA measurement.

Due to the constraints mentioned above, we decided to slightly remodeled the original plan by (i) discussing alternative methods to measure the ¹⁵N-PSIA of these target molecules (ii) building a metabolic model including isotope effects at natural abundance. The latter is of importance to understand the connection between ¹³C and ¹⁵N signatures in cancer cells. Using the model, we were in particular able to show that ¹³C-PSIA of amino acids directly linked to carbon central metabolism (alanine, glutamate, aspartate) could provide important new target molecules for cancer diagnosis (Gilbert & Tea, in prep.). We therefore wish to continue the collaboration with the measurement of ¹³C-PSIA of metabolite from cancer cells and healthy cells.

Related links:
– World Research Hub (WRH) Program
– Gilbert, Alexis