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Alexandra Helleux wins the 2nd jury prize of Ma Thèse en 180 Secondes Alsace

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Alexandra Helleux is a doctoral student at the IGBMC and won the 2nd prize from the jury in Ma thèse en 180 secondes Alsace. The scientist presented her research project on the identification and functioning of a gene responsible for a type of kidney cancer, the TFE3 gene. The aim of her research is to find treatment methods for this type of pathology.

Research into translocation kidney cancer

As a member of the Davidson team and the Malouf subgroup, Alexandra Helleux is interested in translocation kidney cancer, more precisely the types of kidney cancer that involve the TFE3 and TFEB genes. This pathology is characterised by a type of protein called "fusion".

This fusion protein is an abnormal protein derived from a portion of TFE3 associated with a portion of a partner protein produced by an abnormal combination of chromosomes. The formation of this fusion protein is the trigger for tumour formation in the kidney.  Thus, the question Alexandra Helleux is focusing on is: "What is the mechanism by which the TFE3 fusion protein leads to the development of kidney cancer?

 

Looking at the similarities between the partner proteins to understand the mechanism at play

To better understand the mechanism that promotes the appearance of kidney cancer, Alexandra Helleux wishes to understand the effect of the protein produced by TFE3 on the cell. To do this, the doctoral student suppresses the expression of TFE3 RNA in the kidney using a siRNA, a small RNA element whose purpose is to inhibit the expression of a gene. By doing this, the fusion protein cannot be formed, and the PhD student notes that there is only one parameter that changes in the cell: its clonogenic capacity. The scientist observes that the cell's ability to reproduce using its own resources decreases.

"The link between the inhibition of the cell's clonogenicity and the appearance of cancer is not yet clear. Suppressing the expression of TFE3 does not seem to have any impact on the physiology of the cell", explains Alexandra Helleux. "One hypothesis would be that the molecule produced by TFE3 would then interact with a protein normally present in the cell and it would be this interaction that would lead to the development of a cancer", adds the doctoral student.

Another hypothesis formulated by the researcher relates to the conditions of the experiment. In fact, under laboratory conditions, the cell is given "simplified access to glucose in sufficient quantity". By reducing this quantity, she expects to see other effects appear.

 

Better understanding of the mechanism of kidney cancer formation through the animal model

In collaboration with the ICS, Alexandra Helleux is also launching an experiment to overexpress the TFE3 and TFEB genes in the kidney to observe the effects of this overexpression on tumour formation, life span and overall survival in animal models.

With 4 different mouse models involved in the study, the study will ensure that overexpression of the TFE3 fusion proteins and the TFEB protein specifically in the kidney does lead to tumour formation. Once this has been established, an overall survival experiment will be used to assess the time to tumour formation and to collect the kidneys. The aim is to perform DNA, RNA and single-cell analyses to identify early and late mechanisms of tumour formation in mice.

In addition, if the scientist can identify a mechanism that can be modulated at the cell level in the laboratory, the production of the models will make it possible to test the effectiveness of elements to inhibit cancer formation. The production of mouse models makes it possible to understand the impact on the tumour microenvironment, information that cannot be obtained in cell culture. It is particularly important in the case studied by Alexandra Helleux because, depending on the fusion protein observed, the immune infiltration in the tumours may not be the same in the patients.

 

Alexandra Helleux, with two degrees in chemistry and biotechnology, is doing her thesis at the IGBMC

Alexandra Helleux has a degree in chemistry and biotechnology and studied at the ECPM in Cronenbourg and the ESBS in Illkirch. After completing an internship at Matis in Rekjiavic, Iceland, she joined the IGBMC as an engineer in 2019. Initially specialised in single-cell methodology, she passed the doctoral school competition in July 2019. She obtained her PhD and started her thesis in October of the same year.