The efficacy of some established drugs, like the chemotherapy oxaliplatin, may be due to an unknown mechanism: they partition into and disrupt cellular condensates. This reframes our understanding of drug action and could explain why certain drugs are more effective in some cancers than others.
Cells aren't just a random soup or rigidly defined organelles. Condensates form a 'mesoscale' organizational layer. Unlike fixed protein complexes, they have flexible component ratios and are governed by looser rules, providing a dynamic way to concentrate molecules for specific functions.
Instead of targeting individual gene mutations in diseases like ALS, condensate science focuses on shared cellular structures where genetic risks converge. This approach creates a broader therapeutic target, potentially treating more patients with diverse genetic profiles.
Targeting the MYC cancer protein presents a dual challenge. Biologically, it's vital for healthy cells, creating a high risk of toxicity. Biophysically, its disordered, 'floppy' structure lacks the defined pockets that traditional drugs need to bind to, making it a 'holy grail' target.
A major challenge in phenotypic drug screening is determining a compound's mechanism of action. AI models can analyze the complex visual data of cellular condensates after drug treatment, extracting maximal information to understand how the drug is actually working inside the cell.
To target MYC, Dewpoint uses phenotypic screens that monitor the entire MYC condensate. This approach is mechanism-agnostic, capable of identifying compounds that work via previously attempted methods (e.g., disrupting binding) as well as novel ones like dissolving the condensate itself.
Scientist Bede Ports shares that failing out of college, while difficult, built resilience and shaped his leadership. Recognizing he received a second chance that others might not, he consciously incorporates this experience into his mentorship of junior scientists, fostering a more empathetic approach.