Sara McArdle, Ph.D.

Super-resolving cancer immunity

FUNDED: JANUARY 2019

FUNDED BY: The generosity of LJI Board Director Anthony Carr, The Ecke-Meyer Family Foundation, and Bill Passey and Maria Silva.

What was the goal of your SPARK project?

Understanding how the immune system recognizes and responds to cancer is essential for developing treatments that augment our natural defenses. I aimed to develop a brand new technique that allows for single-molecule imaging of human tumor biopsies, which has never been done before. I believe that better imaging will lead to new insights into how immune cells interact with cancer cells and fuel the discovery of new therapeutic targets.

SPARK project results:

My Tullie and Rickey Families SPARK Award made it possible for me to explore a recently developed super- resolution microscopy technique called DNA-PAINT. With this technology, we are closer to developing a method for super-resolution imaging of human tissue sections. Super-resolution microscopy lets us image the interactions between cancer cells and immune cells with unprecedented detail, down to the single-molecule level. There are currently multiple techniques for super-resolution imaging but most require intricate sample preparation protocols which limits its applications. In contrast,

DNA-PAINT is theoretically applicable to a wider range of samples, including tissue sections from patients’ biopsies. I am adapting the existing published DNA-PAINT methods to perform multi-color imaging of clinical tissue biopsies. This will help scientists study the complex interactions between tumors and the immune system. I have also spent the last year working through the processes and pitfalls of DNA-PAINT imaging and taking on major technical challenges in image processing. By investigating these issues, I have gained far more knowledge of super-resolution imaging. I am now better prepared to help any researchers who comes to the LJI microscopy core to perform super-resolution imaging, whether through DNA-PAINT or a different technique.

What’s next for this project?

I plan to keep working towards the goal of super-resolution imaging of tissue sections to help improve cancer immunotherapy targets. The supplies, as well as most of the reagents and samples I purchased for this project, should be stable enough to last another year, so I actually have the resources I need to continue to work on this project. While COVID-19 and subsequent lab shutdowns have made predicting timelines more tricky, I hope that I will succeed in using DNA-PAINT for single molecule imaging of cultured cells within the next year. Once successful, I aim to publish my results to help advance the field of super-resolution imaging for a wider range of applications. This will also be immediately useful to ongoing research at LJI for cancer immunotherapy and other research areas. Furthermore, I used some of my SPARK funds to purchase clinical tumor biopsy samples, which are stable enough to last for years, even decades. After achieving DNA-PAINT imaging in cells and mouse tissues, I plan to use these blocks to perform super-resolution imaging on clinical samples to better understand the distribution of proteins of interest in cancerous tumors.

What’s next for Sara?

In March 2019, shortly after winning my Tullie and Rickey Families SPARK Award I also won an Imaging Scientist Award from the Chan Zuckerberg Initiative. This award provides multi-year funding for experts in core facilities who make novel or complex technologies more accessible to life scientists to help accelerate their research. This 5-year grant means I will stay at the LJI microscopy core, helping both LJI and external scientists perform microscopy studies, including super-resolution imaging through DNA-PAINT.