2021 Michelson Prizes recipient Dr. Rong Ma says the award will serve as a catalyst to provide the freedom she needs to advance her research.
By Justin Chapman
In her spare time, when she’s not studying mechanotechnology and the mechanical forces in the immune system in an effort to advance personalized cancer vaccine development, Dr. Rong Ma enjoys rock climbing.
She looks at tackling a cliff face as a puzzle problem she needs to solve. “I love rock climbing because to me, it feels like doing research,” she said. “You have to use specific techniques and methods to get to the top of the wall. You’re slowly working out this route or way of getting up. It’s like solving a puzzle or a problem. Then you have to execute it. And then you get a lot of fulfillment when you reach the top.”
Dr. Ma will be even better equipped to climb the cliff of her next breakthrough now that the Michelson Medical Research Foundation and the Human Immunome Project awarded her one of the 2021 Michelson Prizes: Next Generation grants. Dr. Camila Consiglio of the Karolinska Institutet and Dr. Nicholas Wu of the University of Illinois at Urbana-Champaign are also recipients of the prize, a $150,000 grant given annually to investigators 35 or younger who are advancing the study of human immunology, vaccine discovery, and immunotherapy.
Dr. Ma’s research is based on novel mechanotechnology, which measures and interprets the mechanical forces involved in the immune system. “I’m trying to answer questions about how the T cells get triggered, but we’re looking at this question through the lens of a biophysical perspective,” she said. “We look at the binding kinetics and the mechanical forces that are transmitted through this activation process.”
T cells defend against infections and cancer by searching for antigens with T cell receptors. Once receptors encounter antigens, they use mechanical ‘tugs’ to determine whether to mount an immune response.
Dr. Ma’s application is based on research that the frequency and duration of these mechanical interactions reflect how closely matched the T-cell receptor is to the foreign agent. Her proposal provides a pathway for using these mechanics to identify an antigen and predict how strong of an immune response a T cell will mount. If successful, it could greatly advance personalized cancer vaccine development. Similarly, vaccine development against viral infections could also use force to identify the optimal antigen for the greatest immune response.
Dr. Ma studied environmental science for her undergraduate degree in China and got her master’s in environmental science and technology at City University in Hong Kong, where she became interested in studying medicinal chemistry and cancer. She then moved to Emory University in Atlanta and joined Dr. Khalid Salaita’s Lab, which specializes in developing molecular tools to study the mechanical forces during cellular processes. She completed her Ph.D. in chemistry just last May. Her research focus has been at the intersection of DNA nanotechnology and immunology.
The high-risk project for which she won the Michelson Prize is a novel method of identifying potential neoantigens and neoantigen-specific T cells. “Neoantigens are expressed on the surface of cancer cells but not on normal cells,” she said. “The problem is, we don’t know which ones they are because every patient is different, with their own tumor mutations. Also, we don’t know which T cells can recognize these neoantigens or which T cell receptors are specifically in charge of binding to this antigen to activate the cell.
“My proposal was to use mechanical forces as a marker of this process so that we can identify the neoantigen itself, the neoantigen-specific T cells, and the T cell receptor that can recognize these antigens,” she said. “The Michelson Prize is coming at a critical time to support me in establishing the proof of concept using a model system.”
Dr. Ma said she was drawn to this work because she became fascinated with how immune cells work. “The immune system is a very delicately dictated defense mechanism,” she said. “It’s super sensitive, precise, and dynamic. For a T cell, even just a few of the interactions with a potent antigen is enough to trigger its activation and consequently raise a red flag for the whole immune system. It’s hard to imagine cells can do that. It’s just so fascinating.”
Dr. Ma said receiving the Michelson Prize will be helpful in terms of the support and access to resources that it will bring to her research. She also expects that it will allow her to grow her team.
“Right now, because I’m still a postdoc, I don’t have much independence, but with the prize, I will have a lot of independence in driving this project forward,” she said. “I will be able to directly contact labs that I wish to collaborate with and have access to their resources. So it’s very critical. It’s going to be a catalyst for me, for this project. It’s really important.”
She also offered advice to future researchers who are considering applying for the Michelson Prizes. The 2022 application opens on April 1.
“I feel like I’m still in a very early stage of my career to give advice, but one suggestion I could give is, whenever your hypothesis is proven wrong, or experiments are not working in the lab, don’t get discouraged,” she said. “I know sometimes a lot of people do get frustrated when things are not working in the lab. But that’s very normal. And as researchers, I think it’s a very important quality to take a failure in the lab and change it into something that is going to work for something else.
“You have to be flexible and perceive it not as a failure but as a window, a path to a new finding. That’s a very good mindset to have, especially if you’re spending many hours in the lab. You have to be positive.”