[LUM#12] Karma's Female Researchers
Imagine a molecular scissors capable of breaking down a protein by cutting it exactly where you want. Karma is the name of this project, developed by fourteen students from Montpellier and recognized at the prestigious international synthetic biology competition held annually in Boston.
“In many diseases, such as cancer or Alzheimer’s, research has identified the role played by certain proteins in the development of the disease,” explains Thomas Bessede, a first-year master’s student in the BIOTIN program (Master’s in Health Biology). “Current drugs use chemical molecules to block them.” The problem is that these pharmaceutical molecules do not always target the proteins in question and therefore cause side effects.
Molecules capable of breaking down proteins occur naturally in our bodies; these are called proteases. Some of them are highly specific and can effectively target a particular type of protein.“Unfortunately,” explains Elsa Frisot, a PhD student at CBS and the team’s supervisor, “we don’t have a specific protease for every type of protein, and while nonspecific proteases do exist, they too carry the risk of causing side effects.”
A researcher
The fourteen students participating in the IGEM (International Genetically Engineered Machine) competition set to work on this problem and devised a revolutionary molecular tool: a protein-based pair of scissors capable of breaking down proteins in a highly targeted manner.“We drew inspiration from the CRISPR-Cas9 tool, a genetic scissors capable of targeting and cutting a specific DNA sequence,” notes Thomas Bessede.
To develop this tool, the team turned to antibodies, whose strength lies in their ability to specifically target a protein, much like a“homing device .” “Today, in the lab, we’re able to design antibodies for just about anything. Each antibody has the ability to bind to a specific target.” Among these antibodies, the IGEM team selected VHH and fused it with a non-specific protease to deliver it to the desired target.
A successful experience
To observe the effect of the Karma scissors on a target protein, the young biologists used GFP, a protein that emits green fluorescent light.“For the experiment, we added a small tag to the GFP that blocks this fluorescence. The goal was to guide our protease, equipped with a VHH, to this tag in order to degrade it and allow the GFP to glow again,”Thomas explains. And the experiment was a success!
Having garnered recognition and awards in Boston, the Karma project now lies dormant in the CBS freezers, in the hope that a motivated researcher will continue the experiment to fully realize its potential and perhaps discover new therapeutic applications. You can read more about this project on the IGEM 2019 website.
UM podcasts are now available on your favorite platform (Spotify, Deezer, Apple Podcasts, Amazon Music, etc.).