Science with Sandra and Dr. Abraham Al-Ahmad

Hello and welcome to Science with Sandra!

For this edition, I would like to highlight an ongoing study from an esteemed researcher in our community, Dr. Abraham Al-Ahmad. Dr. Al-Ahmad is an Assistant Professor of Pharmaceutical Sciences at the School of Pharmacy at Texas Tech University in Amarillo.

The title of his publication, in pre-print, is “GLUT1 truncation in HEK293 cells compromises glucose uptake and energy homeostasis and induces cellular morphological changes metabolic rewiring”.

The purpose of the study is to develop a screening platform to perform genotype-phenotype association studies using HEK293 cells. HEK 293 cells are a cell line generated from human kidney cells that were transformed using a human adenovirus and are commonly used in research because they are easy to grow, among other things. It is important to point out that in addition, GLUT1 protein is the major glucose transporter protein (GLUT) expressed in this cell line, which is key for this study.

What is the research about? 

Dr. Al-Ahmad and his team modified the SLC2A1 gene which encodes for the GLUT1 protein in HEK293 cells, generating a truncated (shortened) version of the protein making it non-functional. The genetic editing of the SLC2A1 gene in HEK293 cells generated a clone of cells lacking a full-length GLUT1 protein/transporter.

What are their findings?

1. The modified cells (clone E11) do not produce a full length GLUT1 protein/transporter.
2. The cells from the new clone (E11) are still viable (alive), but they grow at a slower rate and show different morphology (shape) and motility (the way they move) compared to control cells.
3. The shortened GLUT1 shows a significant effect in cell metabolism. E11 cells show a decreased glucose uptake, as well as decreased lactate production. 
4. The effect of truncating the GLUT1 protein in clone E11 is not compensated by other GLUT proteins present in HEK293 cells.

Some of their conclusions so far are that the truncation of the GLUT1 protein has a significant effect on HEK293 energy metabolism, with a critical effect on glucose metabolism by impacting glycolysis and oxidative phosphorylation, while relying more on the pentose phosphate pathway (PPP).  Oxidative phosphorylation in simple terms is the production of ATP in the presence of oxygen, while PPP is important to maintain carbon balance, to provide precursors for important components for DNA, RNA and proteins and other important components in cellular metabolism.

Why is this study important? 

This study will provide a new cell model for researchers as a useful tool to:

1. Show how different mutations or variants on the SLC2A1 gene affect its function.
2. As a potential screening platform for genotype-phenotype association studies focusing on GLUT1.
3. As a platform to test new possible treatments for Glut1 Deficiency.

We thank Dr. Al-Ahmad and his team for his continuous support and for being a key research collaborator in our community!

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