BRI recently launched our new Innovation Fund to support early-stage research ideas and develop and implement new tools and technologies. Powered by philanthropy, each study acts as a pilot project. First, grantees get new tools and technologies up and running and use them to ask exciting new research questions. Then, BRI scientists will have access to these new tools and apply them across labs and disease areas.

The inaugural grant was awarded to Jessica Hamerman, PhD, and John Ray, PhD. Together, they’re exploring the genetic roots of autoimmune disease using a state-of-the-art technology called single-cell CRISPR screening.

We recently asked them about their work and the new possibilities that single-cell CRISPR screenings will open up at BRI.

Tell me more about your project. What is your team hoping to learn?

Dr. Hamerman: Broadly, we’re examining the role genes play in autoimmune disease using a new technology called single-cell CRISPR screening. It’s a two-part project. The Ray Lab is working to understand how different gene regulatory regions control T cell function in autoimmune disease while my lab is focusing on genetics in lupus nephritis (lupus-related kidney disease).

Tell us more about the new tool you’re implementing. What is it, and why is it exciting?

Dr. Ray: CRISPR is a genome editing tool that allows you to study cause and effect. You can perturb (change or knock out) one part of the genome in the lab and see how that changes a disease process. Before this funding, we were doing bulk-cell CRISPR screenings. Those screenings are good, but they only allow you to study a single effect of a genetic change at a time, and don’t provide data about what’s happening in individual cells.

With single-cell CRISPR screenings, we get a lot more granular. In addition to seeing cause and effect, we see how any given perturbation affects thousands of other genes across many different cell types in individual cells. Our biggest screen is looking at about 80 changes and their effects on many immune cell types.

Dr. Hamerman: This technology is opening the door to some really rich information. In lupus nephritis, we’re knocking out specific genes and seeing how each affects a cell type called monocytes. We’re specifically looking at their ability to go into the kidney and cause lupus nephritis. This is really exciting because if we can understand the role genetics plays in driving those cells into the kidney and causing damage, it opens up new potential ways to stop that process and treat the disease.

What’s really powerful about these pilots is that after the initial study, anyone at BRI could use this technology. So my experiment is looking at monocytes in lupus, but another scientist could just as easily do a screen of T cells in type 1 diabetes or any other cell in a different disease.

How do you collaborate with each other?

Dr. Hamerman: John and I study really different things. Combining our expertise — me in models of lupus and him in genetics of autoimmunity and CRISPR screening — enables us to do something that neither of us could do alone. This type of collaboration is so valuable because it accelerates the pace of discovery by forming partnerships, rather than either of us having to stop and learn an entirely new skill. Plus, the collaboration piece makes this work way more fun.

Down the line, how do you hope this work will help predict, prevent, reverse and cure immune system diseases?

Dr. Ray: My hope is that this research will help identify more targeted ways to treat lupus and other autoimmune diseases. Right now, we don’t have targeted treatments for many autoimmune diseases. This is especially true in lupus. Instead, we use treatments that slow down the whole immune system, which could leave patients vulnerable to infections like COVID-19.

We also don’t fully understand how or why lupus nephritis develops. So understanding how the disease starts and progresses at a really fundamental level could open up new avenues for ways to treat it.

Why is philanthropy to support new research avenues and technologies important?

Dr. Ray: This funding is crucial because it's very rare to get funding to test and implement new technologies. This funding not only gives us the chance to try a new tool, but also to create preliminary data that prove we can use these new technologies for other larger grant submissions.

It’s called the Innovation Fund for a reason: It allows us to answer questions that we weren't able to before. I believe bringing in new technologies gives us the best chance to do cutting-edge science. And cutting-edge science is how we develop new treatments faster. For BRI to stay on the cutting edge of research, implementing these tools is not optional, it's essential. We’re grateful for our donors who make this possible.

Make a donation to support BRI's Innovation Fund