[LUM#12] The Karma seekers
Imagine a molecular scissor capable of degrading a protein by cutting it exactly where you want it. Karma is the name of this project by fourteen students from Montpellier, which won an award at the prestigious international synthetic biology competition held every year in Boston.
In many pathologies, such as cancer or Alzheimer's disease, research has identified the role played by certain proteins in the development of the disease," explains Thomas Bessede, a student in Master 1 BIOTIN (Master Biologie santé). Current drugs use chemical molecules to block them ". The problem is that these pharmaceutical molecules don't always target the incriminating proteins, and therefore cause side effects.
Molecules capable of breaking down proteins exist naturally in our bodies, and are known as proteases. Some of them are highly specific and can effectively target a particular type of protein. Unfortunately," explains Elsa Frisot, a doctoral student at CBS and the team's supervisor,"we don't have a specific protease for every type of protein, and while aspecific proteases do exist, here again they run the risk of causing side effects. "
A research head
The fourteen students taking part in the IGEM (International Genetically Engineered Machine) competition tackled this problem and came up with a revolutionary molecular tool: a protein scissor capable of degrading proteins in a highly targeted way. " We were inspired by CRISPR cas 9, a genetic scissor that can target and cut a specific DNA sequence," explains Thomas Bessede.
To create this tool, the team turned its attention to antibodies, whose strength lies in the fact that they are truly designed to target a protein, like a kind of " seeker-head ". "Today in the lab, we can design antibodies for anything. Each antibody has the ability to bind to a specific target. Among these antibodies, the IGEM team selected VHH and fused it with an aspecific protease to bring it to the desired target.
A successful experiment
To observe the effect of the Karma scissors on a targeted protein, the young biologists used GFP, a protein whose particularity is to diffuse green fluorescent light. " For the experiment, we added a small tag or label to the GFP to block this fluorescence. The aim was to guide our protease equipped with a VHH onto this tag in order to degrade it and allow the GFP to glow again ", describes Thomas. And the experiment was a success!
Recognized and rewarded in Boston, the Karma project now sits patiently in the CBS refrigerators, in the hope that a motivated researcher will extend the experiment to develop its full potential and perhaps find new therapeutic applications. Find out more about this adventure on the IGEM 2019 website.
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