Lucy Shapiro, PhD, untangles the genetic circuitry that makes life possible

“Our two teams were able to explore the physics and chemistry of life side by side, and that revolutionized our understanding of the most abundant organism on the planet.”
- Lucy Shapiro, PhD

Life is a collaboration between thousands of genes, all working together to produce a functioning organism. Lucy Shapiro, who is the Virginia and D. K. Ludwig Professor of Developmental Biology at Stanford, has spent years studying bacteria to learn how genes orchestrate all the complexities of life. Her quest has resulted not only in new insights into how life works, but strategies to design new antibiotics.

“As time goes by,” Lucy says, “every single available antibiotic is becoming increasingly useless.” Every year at least 23,000 Americans die of drug-resistant bacterial infections, and the approaches currently used to discover new antibiotics are failing. But with their research on the bacterium Caulobacter crescentus, Lucy and her colleagues are finding new approaches to this global problem.

Working with her husband, physicist and professor of developmental biology Harley McAdams, PhD, and their combined research teams, Lucy mutated Caulobacter cells so that each had a snippet of artificial DNA inserted at a random spot around its single, ring-shaped chromosome. Tagged to be found later, these segments disrupted genetic function wherever they landed. After letting the cells multiply for a few days, they sequenced the DNA of the survivors. Those genes that tolerated the inser tion of ar tificial DNA weren’t essential for viability, while those that didn’t tolerate it were essential to life. The essential genes comprised 12 percent of Caulobacter’s genome, and many were part of a complex genetic circuit that integrates multiple cell functions.

With this technique Lucy, Harley, and their teams can quickly identify which genes are essential for survival in almost any microbial species. They can then target the functions those genes control to create antibiotics that are “resistant to resistance” because they attack multiple vulnerabilities simultaneously. They already have several in clinical trials.

By combining talents and teams, Lucy and Harley have given the world a better understanding of bacteria and a better way to develop desperately needed drugs. “His students have been physicists and engineers, while mine have been biologists and geneticists,” Lucy says. “They work side by side.”

Despite the potential of interdisciplinary collaborations like this, they are often excluded from the narrow purview of many funding agencies. This creates a vital and exciting role for philanthropists – by helping scientists from different fields collaborate, they can be part of a team that changes the world.