The core hypothesis under investigation is that manipulating key condensate scaffolds hinders disease-driving processes without interfering with the enzymology required for physiological cell functions.
The strategy followed to tackle this hypothesis entails:
We will develop assays specific to each disease-specific condensate to detect the drivers of disease. for example, we will use proximity labelling to identify scaffolds of metabolic enzymes involved in driving cancer metastasis. Then, we will perform RNAi screens to confirm the involvement of candidate scaffolds in the formation of disease-relevant condensates. Finally, we will perform immunolabelling for co-localisation studies to confirm the interaction between the scaffold and metabolic enzymes.
- Performing biophysical characterization of condensate scaffolds and their separation properties
- Establishing and manipulating the molecular grammar of scaffold formation
- Testing the role of identified condensate scaffolds in disease progression
The main output of this research would be to detect and control disease relevant biomolecular condensates.
Return to phase separation
Patel et al
Klosin et al.
Guillén-Boixet et al.
Unfolded mRNA facilitates G3BP conformational switching and condensation