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What is Cell Painting?

What is Cell Painting?

Using florescent stains, researchers can light up a cell’s parts and study changes. The method, CU computational cell biologist Michael Lippincott explains, is enhancing the way he and other biological data scientists can obtain information and learn more about cells and human health.

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Written by Kara Mason on November 8, 2023

Computational cell biologist Michael Lippincott, a PhD student in the Department of Biomedical Informatics at the University of Colorado School of Medicine, spends his days studying cells, how they approach death, and then how they die.

In his work in the Way Lab, Lippincott often utilizes cell painting, a method that uses fluorescent dye to light up a cell’s parts to more easily show changes. Academics originally honed the technique, but pharmaceutical companies quickly took interest because cell painting can help researchers understand how a drug affects a cell.  

“There are many applications for cell painting,” Lippincott says. “This method allows for some creativity in the scientific process because the sky is the limit.”

Not to mention, the paintings themselves are their own works of art.

“They almost look like holiday lights in some paintings,” the researcher says. “Along with the painting, there are gigabytes upon gigabytes of data that different machine learning algorithms can analyze. You start with a cell, and on one side you have art and on the other you have numbers. That duality is really intriguing.” 

Lippincott explains the technique, why it can be so helpful to medical researchers, and how the method is evolving.

Q&A Header

What is cell painting and how does it work?

It’s a technique that’s widely used in the cell biology community that allows us to view the different compartments of a cell. There are different layers to a cell and its machinery has different functions. We can basically color-by-number those compartments with fluorescent stains. That allows us to learn how the cell overall is changing during a given process that we would like to study.

What kind of information can you gather from looking at cell paintings?

There is a lot we can learn from this process. We can look at how the organelles inside the cell change or how the cell’s machinery changes. The idea in biology is that size and shape equal function, so if the size and shape of a piece of the cell are changing, then the function is too.

So, somebody in the lab will paint the cell, then you’ll get that image and analyze it from there?

Yes, exactly. In conjunction to using open source software, our lab has developed software that can process the images, correct them, and then we send those images through a whole computational pipeline. At the end, we do something called feature extraction, which is essentially a targeted measurement. This software can take more than 3,000 individual measurements, telling us how a cell changes and how that cell changes on each of the cell sub compartments and organelles.

How is the technique evolving and what are you looking forward to in the future?

Cell painting is a fairly new technique, and it’s built off the concept of fluorescence, which basically shines a flashlight on a particular protein. Cell painting is affordable and the compounds used don’t target just one particular protein, they target proteins that are associated with each of the different machineries in a cell. This means that it’s extraordinarily generalizable in the sense that two different people can do the same experiment in two different cells, studying two different systems and they can both still understand what the other is doing.

But like anything else there’s a caveat, and perhaps the most notable for cell painting is that to actually stain or “paint” a cell you need to fix the cell. A chemical treatment freezes the cell in place and everything that’s happening within it, so you’re not necessarily working with live cells. There is one novel technique that is very similar to cell painting that allows researchers to watch a live cell, and that is an interesting process as well.

It sounds like this can be impactful for research.

That’s right. There are periods of scientific booms and prolific research after a major technological or methodological innovation. For cell biology, it goes all the way back to the invention of the microscope. Right now, we have a technological ability to use very large data and machine learning in research, so being able to collect that data, like in cell painting, is enabling us to do bigger and better things than ever before.

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Michael Lippincott