A technique called Cell Painting could speed up drug discovery

Now some are adopting a new paradigm: measure everything, ask questions later. This motto directs a lab at Harvard and MIT’s Broad Institute, where researchers have developed a method to generate a treasure trove of information about a cell’s inner workings that they can sift through for years. The method, known as Cell Painting, impressed scientists from several pharmaceutical companies so much that they started a consortium and pooled their resources, using this approach to create a massive dataset that they started to be released to the public in November. The JUMP–Cell Painting Consortium, as it’s called, hopes the database will speed up drug discovery by helping researchers identify promising compounds and get a better idea of ​​what they do and what types of side effects they might have before the molecules are tested on animals or people.

Cell Paint uses up to six fluorescent dyes to illuminate key components of the cell, such as the nucleus and mitochondria. A microscope takes images of the different spots and software measures morphological characteristics such as size, shape, intensity and texture, creating a profile based on the image of the sample. It’s “pretty much the easiest imaging test you can manage,” says computational biologist Anne Carpenter, who developed the method and co-directs the Broad Institute lab with Shantanu Singh. “Our mission was to choose the cheapest and simplest dyes.”

Beyond ease of use, the power of Cell Painting lies in the sheer volume of data from an experiment. The recently released database contains images of cells responding to more than 140,000 disturbances, either drug treatment or some other change that increases or decreases the activity of a gene. Using this dataset, Carpenter and some of his colleagues found a dozen compounds that appear to affect the same structures that are influenced by a key gene implicated in fast-growing muscle cancer. Rather than subjecting hundreds of samples to multiple rounds of wet lab experiments, Broad researchers listed the drugs several years ago by typing the gene’s name into the database.

“It’s a totally different approach that involves far fewer steps and is far less expensive,” says TS Karin Eisinger, a biologist at the University of Pennsylvania who studies this particular muscle cancer. His team worked with Carpenter’s to validate the compounds in wet lab tests, and the two scientists are starting a company to further develop the most promising candidates. Others are a bit more advanced: Recursion Pharmaceuticals, a Salt Lake City company for which Carpenter advises, has already launched five clinical trials to test drug candidates identified using a version of Cell Painting.

As it completes its public release, consortium members are preparing to work with the Washington, D.C.-based Institute for Health and Environmental Sciences to see if they can link the paint results. cell to other data to predict the toxicity of pharmaceuticals and agrochemicals. .

Esther Landhuis is a science and health journalist based in the San Francisco Bay Area.