Lasker Award for Uncovering Spatial Organization in Bacterial Cells

The Lasker Foundation announced this year’s winners of the Lasker Awards today (September 11). Lucy Shapiro, a developmental biologist at Stanford University, won the 2025 Lasker-Koshland Special Achievement Award in Medical Science for a 55-year career in biomedical sciences that revolutionized the understanding of spatial organization in bacterial cells. Her pioneering discoveries laid the groundwork for the development of novel drugs to combat antimicrobial resistance and infectious diseases.

“I was quite shocked, truly,” said Shapiro, about receiving the news. “The Lasker Special Achievement Award has been given over the past 30 years, every other year, to my heroes. And to be included in that cadre was an overwhelming honor.”

Over the past half a century, Shapiro’s work on the bacterium Caulobacter crescentus has provided insights about how the genetic circuits of a cell dictate its spatial dynamics, which in turn modulate genetic regulatory pathways. This research overturned the then-prevalent viewpoint that bacterial cells are sacs of jumbled enzymes. She eventually translated her knowledge to develop two FDA-approved drugs: one antifungal and another to treat eczema. In addition to being one of the researchers who established the field of systems biology, she also served as a scientific advisor to the White House.

From Fine Arts to Caulobacter crescentus

Born in 1940, Shapiro trained as a painter, majoring in Fine Arts and minoring in Biology during her undergraduate education at Brooklyn College. This unique combination sowed the early seeds of her interest in understanding the three-dimensional environment within cells.

“The way in which my brain works, I see things easily in three dimensions,” said Shapiro. “I have an eidetic memory, which means I photograph things in my head, and that led to me viewing biology in a spatial context.”

After finishing college, Shapiro joined New York University in 1962 as a lab technician, and eventually as a graduate student under Thomas August, tasked with studying RNA-dependent RNA polymerase. The department moved to Albert Einstein College of Medicine, from which Shapiro graduated in 1966.

Six months later, at the age of 26, biochemist and department chair Bernard Horecker, offered her a faculty position in the same department. He advised her to decide on her research focus first. “[He] said, ‘Take three months and think. Don’t go into the lab; just think and decide, what is the question, the critical unanswered question that you can hang the rest of your scientific career [on],’” recalled Shapiro. “And that was an incredible gift.”

She dove into the literature and realized that scientists were busting open cells to perform in vitro assays to understand bacterial cell biochemistry. “It occurred to me that what we had to know was really going on inside a cell and not just inside a test tube,” said Shapiro. Leaning on her training as a painter-turned-biochemist with a vision of cells as three-dimensional entities, Shapiro identified a crucial unanswered question: How does linear DNA encode cells’ biochemical activities in three-dimensions?

“Up to that point, the bacterial cell was assumed to be a swimming pool with the DNA [being] just a ball of spaghetti floating around,” said Shapiro. But she was confident that there was a logic that dictated how a cell decoded information about its three-dimensional structure from its linear DNA.

In her quest to answer this question, she dug deeper into the literature to look for a simple cell type that exhibited polarity and yielded two distinct daughter cells during division. She landed on C. crescentus, a crescent-shaped bacterium that has a flagellum at one end and a stalk-like appendage at the other. It also splits asymmetrically: Cell division gives rise to one mobile, flagellum-containing swarmer cell, and another immobile, stalked cell. Swarmer cells transition into stalked cells before undergoing cell division.

Shapiro decided to investigate how the bacterium’s genome dictates the asymmetric cell division, even though the microbe was difficult to grow and not well-studied. “I didn’t know that you don’t look at a bug that nobody knows anything about,” she said.

Piecing Together the Logic that Dictates Bacterial Lives

Despite the challenges that the model system presented, Shapiro—who relocated to Columbia University in 1986 and to Stanford University in 1989—and her team demonstrated that bacterial cells are highly organized: In 1993, they found that chemoreceptor proteins that regulate bacterial chemotaxis in response to environmental cues were localized to one pole of the cell.¹

By investigating genetic mechanisms that controlled flagellar formation in the bacterium, Shapiro and her team discovered the genetic hierarchy underlying flagellum biosynthesis.² While studying mutants that did not produce flagella, the researchers identified a gene encoding a response regulator, CtrA, that controls the transcription of genes encoding important flagellar and chemotaxis proteins.³

The researchers discovered that swarmer cells contain CtrA, which gets degraded by proteases located at the cell pole during the swarmer-to-stalked cell transition, revealing a delicate temporal and spatial organization in the cells.⁴

Around this time, Harley McAdams, a physicist then at Bell Labs and Shapiro’s husband, recognized the parallels between the logic of electrical circuits and genetic regulation.⁵ Shapiro and McAdams opened a joint multidisciplinary lab where biologists, engineers, and physicists worked together to uncover the genetic and spatial controls in bacterial cells. “It was phenomenal. It was like a cauldron,” said Shapiro. “We were learning each other’s languages. We were learning each other’s ways of thinking, and that was critical. We were…deeply exploring what it means for a cell to be alive.”

This collaboration was a stepping stone for establishing the field of systems biology, an interdisciplinary area that uses computational tools to understand how living systems function. Shapiro and McAdams’s efforts eventually culminated in breakthrough findings: They discovered that in addition to controlling flagella and chemotaxis, CtrA controls the transcription of hundreds of genes, including the ones that coordinate the cell cycle.⁶ This discovery of a master regulator proved to be a turning point in exhibiting that cells contain an inherent logic wherein the turning on or off of certain genetic circuits in a specific order drives the cell cycle.^7,8

“When we discovered that there were a small number of molecules controlling the entire circuitry that gave you the logical progression of the cell cycle in time and space…I think [that] was the most thrilling moment of my life,” said Shapiro.

As sequencing and imaging tools became increasingly sophisticated, in 2004, the researchers went on to show that bacterial chromosomes, too, exhibit a much higher degree of spatial organization than previously thought. They found that chromosomal loci localize to a specific site during distinct steps of DNA replication.⁹

These pieces of evidence helped Shapiro and her team solve the puzzle of how C. crescentus divided asymmetrically: They found that different localization of molecules in the cells creates a gradient of active CtrA before cell partitioning, resulting in the initiation of different genetic programs in each daughter cell immediately after division.¹⁰

Translating Knowledge from Bench to Bedside

At the turn of the century, Shapiro grew increasingly concerned about the growing antimicrobial resistance and threat of infectious diseases. By this time, she had been part of the advisory boards of biotechnology and pharmaceutical industries. She teamed up with a fellow board member from one of the companies, Stephen Benkovic, a chemist at Pennsylvania State University, to develop a new class of antimicrobials with boron—instead of carbon—at the drugs’ active site.

Others were skeptical due to the unconventional drug design, but Shapiro and Benkovic pushed through and found that the compounds were both safe and effective. The two founded Anacor Pharmaceuticals, which produced two FDA-approved topical drugs for eczema and fungal infections, before being acquired by Pfizer in 2016. Then, the pair switched lanes to prevent plant fungal infections, which were increasing with climate change. They co-founded another company called Boragen, now 5Metis, where they developed a compound that attacks a fungus that infects banana plants.

Even as she took on this important challenge for the betterment of humanity, she never forgot her roots. “Even though I was doing all this other stuff, 75 percent of my life was in my lab, and that never stopped,” she said.

Looking back, Shapiro said her career has been full of exciting and fulfilling moments. But to her, the future looks grim. “I’m concerned that the exquisite scientific endeavor that has been built in the United States is under threat,” she said. “We need scientists who are deeply embedded in the truth, deeply embedded in knowledge. It’s extremely important that we all as scientists have to talk, have to get out there and describe what we do.”