2019 – 2020 Highlights

Dr. Konermann obtained her Ph.D. in neuroscience at MIT, doing doctoral work with Feng Zhang, Ph.D., at the Broad Institute. She then did postdoctoral work with Patrick Hsu, Ph.D., at the Salk Institute for Biological Studies, where she discovered a new family of RNA-targeting CRISPR nucleases and harnessed it as an efficient tool for programmable RNA perturbation and the reduction of pathological tau isoforms in a model of frontotemporal dementia.

As a graduate student, Dr. Konermann focused on the development of technologies to enable efficient, generalizable, and precise perturbation of mammalian gene expression. Dr. Konermann developed the first tool for optogenetic manipulation of endogenous mammalian transcriptional and epigenetic states in the mouse brain. She also uncovered the biochemical mechanism of the first single effector RNA targeting CRISPR enzyme, C2c2. Currently, she is applying multiple modes of targeted transcriptional perturbations to understand genetic interactors of APOE in late-onset Alzheimer’s disease.

Last year, the flu virus killed more than 50,000 people in the United States alone. The team working on this new approach is led by Beckman Center scientist Peter S. Kim, Ph.D., the Virginia and D.K. Ludwig Professor of Biochemistry and the lead investigator of the infectious disease initiative at the Chan Zuckerberg Biohub.

The new approach involves the use of a monoclonal antibody that can bind to the exact spot on the flu virus protein that researchers want the immune system to recognize. Using the monoclonal antibody as a stencil, the rest of the protein can be “painted” with molecules that act as a chemical cloak, rendering it invisible to the immune system. Removing the stencil then leaves only a tiny portion of the protein visible for the immune system to learn to recognize and eventually attack.

Lab animals that received the cleverly cloaked flu protein also showed an immune response to other strains of the flu—something that would happen only if their immune systems had learned to recognize the viral core. Animals that received a normal vaccine didn’t respond well to other flu strains.

Dr. Bejerano’s group developed an unbiased way to sift through whole genome sequences and spotlight concerted genetic changes shared by animals with unusual abilities or traits. Remarkably, the researchers found that their unbiased analysis homed in on the cochlear ganglion as the single most affected tissue among echolocating mammals. “Pulling the cochlear ganglion—a real poster child for the development of echolocation—out of a hat containing more than 4,000 possible gene sets, based on genomic sequence alone, was pretty spectacular,” said Dr. Bejerano.

“This study is a great example of what we can accomplish when we combine the data in whole genome sequences from multiple species with functional information about specific genes,” he said.

The scientists have shown that blocking this signal in mice implanted with human cancers allows immune cells to attack the cancers. Blocking other “don’t eat me” signals, such as CD47, has become the basis for other possible anti-cancer therapies.

Of particular interest was the discovery that ovarian and triple-negative breast cancer, both of which are very hard to treat, were highly affected by blocking the CD24 signaling, pointing to a potential vulnerability for those very dangerous cancers.