Perennial Explorer: A Profile of Neelima Sinha

This University of California, Davis, botanist studies the genes that regulate plant anatomy.

Feb 1, 2019
Anna Azvolinsky
Neelima Sinha
  • Professor, Department of Plant Biology, University of California, Davis
  • Katherine Esau Junior Faculty Fellow (1997-1999)
  • Chancellor’s Award for Excellence in Undergraduate Research Mentorship (2001)
  • Elected Fellow of the AAAS (2006)
  • Benjamin Peary Pal Chair of the Indian National Scientific Academy (2015)
  • The Pelton Award – Botanical Society of America (2016)
  • Fellow of the American Society of Plant Biologists (2018)
© courtesy of David Slipher

Plant biologist Neelima Sinha was 30 years old when she entered graduate school in botany at the University of California, Berkeley. “It doesn’t seem terribly old now, but I was a lot older than the other students around me,” she recalls. Although Sinha had “desperately wanted to do research and get a PhD” after receiving her master’s in botany from Lucknow University in India, her own practical inclinations and her mother’s guidance steered her to take the civil service exam to explore her career options. “My mother wanted me to be independent, and I think she thought that doing a PhD was a long road and that I would need someone to support me in order to complete it,” she says.

So Sinha worked as a bank manager for nine years, earning a good living and achieving the independence her mother had envisioned. On the job, she met her husband, Ranjan, who had an engineering degree. Ranjan, like Sinha, was increasingly disenchanted by his job in finance. “Suddenly, we both decided that we wanted to go back and pursue PhDs. We had money saved up and started to prepare, studying for the GREs and applying to schools at night after work. I was studying for the GRE biology subject test and thought, ‘This is what I want to be doing,’” Sinha says.

In 1985, with their 5-year-old son Bhaskar in tow, Sinha and her husband arrived in Waco, Texas, to attend Baylor University, where Ranjan entered a 1-year MBA program, and Sinha was to do a 1-year master’s program in environmental studies. “We had never traveled outside of India, and landing in Texas was like arriving on another planet. Some people were very welcoming and others were not so welcoming,” she says. “People would stop me in grocery stores and ask if I was Christian, and someone actually asked me if, in India, people still lived in trees.” Along with the culture shock, the couple also worried about readjusting to life in an educational institution, as they’d both been out of school for almost a decade. “Initially, we took a year leave of absence from our jobs to see if we could even do academia after such a long time away,” Sinha says. The time away from school turned out not to be an issue, and after six months at Baylor, both Sinha and Ranjan were applying for PhD programs.

In 1986, the family moved to Berkeley, California, where Sinha started her PhD research in botany and Ranjan began a PhD program in accounting. “We were both happy when we arrived at Berkeley, which was a completely different experience,” she says. “People there were very welcoming.” The family later moved to Boston for Ranjan to take a job, and then Sinha landed a faculty position at the University of California, Davis, where she’s been ever since.

Early enchantment

Sinha was born in 1954 in a small town near New Delhi, India. Her father worked in the state government, and his position meant that the family—including Sinha’s brother, Prakash, who is eight years younger, and her sister, Sudha, who is eight years older—moved to a new city every three years or so. “I didn’t have many friends growing up as a result,” Sinha says. “I just remember a lot of packing boxes!” Sinha’s parents—particularly her mother, who only received her high school certification after the birth of her first daughter— prioritized education. Sinha attended all-girls’ Catholic schools, which she remembers fondly. “We were a Hindu household, but I still have a very soft spot for Irish Catholic nuns. I only have good memories from the schools I attended,” she says.

We had never traveled outside of India, and landing in Texas was like arriving on another planet.

Sinha’s fascination with biology started around age 8, she recalls. By high school, she was so enthralled with the subject that her parents bought her extra biology books to read at home on everything from how seed germination works to how the human kidney functions. She had an “incredible” 11th grade biology teacher, a nun who had a master’s degree in zoology and who led Sinha’s class on dissections of creatures from across the animal kingdom: “Earthworms were OK, cockroaches were maybe OK, but when we got to the warm-blooded creatures like the pigeon, I just couldn’t handle it,” she says. Her visceral reaction to the animal dissections drove her to study plants.

Perhaps not surprisingly, when Sinha entered college at India’s Lucknow University in 1971, she studied chemistry and animal science but majored in botany, particularly immersing herself in paleobotany and the history of plant life on Earth. She graduated with her master’s in 1975, but Sinha made the pragmatic decision to go into banking. After a few years, however, she realized that her banking career was not fulfilling enough and that academia was where she, and her similarly frustrated husband, belonged.

Auspicious beginnings

At Berkeley, Sinha joined Sarah Hake’s lab, which was focused on the genetics of plant development. Hake was then a new faculty member who was also a joint appointee at the United States Department of Agriculture’s new Plant Gene Expression Center (PGEC), and Sinha was her first graduate student—one who had never performed genetics or molecular biology experiments. Sinha worked hard, absorbing all of the techniques she could from Hake and others in the lab and ultimately choosing to study a genetic mutation in maize called KNOTTED that disrupts normal leaf development, turning the normally smooth corn leaves bumpy—a result of cells within the leaf adopting inappropriate cell fates. Sinha investigated the developmental characteristics of these mutants, showing that the knot-like nodules originated in the innermost leaf layer. The gene that was mutated, called KNOTTED-1, turned out to be among the first homeobox genes, a large family of similar genomic elements that direct the formation of many body structures during early development, found in plants.

Greatest Hits

  • Uncovered the role of KNOTTED-1 in leaf development in maize.
  • Established that the maize homeobox gene KNOTTED-1 can regulate leaf cell fate and that modulating the expression of this gene can result in cell fate switch within leaf structures.
  • Analyzed the evolutionary origin of homeobox genes in the ancestors of plants, fungi, and metazoans.
  • With colleagues, found that similar leaf structures are not necessarily homologous among plants and that KNOX genes are involved in generating compound leaves in many diverse plant groups.
  • Demonstrated host-induced gene silencing, where small interfering RNAs expressed in a host plant can lead to silencing of genes in a parasitic plant.

Homeobox genes typically encode transcription factors that bind to DNA and selectively turn certain genes on or off. When Sinha began to study the genes, they were relatively well characterized in animals, such as in Drosophila, but not in plants.

Intrigued, Sinha started worked on cloning homeobox genes in tomato plants and studying their function. “I called it my ‘nine pm to midnight project,’” she says. Sinha would go home to be with her family for dinner, put her son to bed, and then come back to the lab. After a few years, she discovered that homeobox genes in plants influenced leaf development. In 1993, she reported that when KNOTTED-1 was overexpressed in the tobacco plant, the plant’s leaf cells switch fates, causing shoot structures, for example, to form on leaves.

Tomato jam

When it came time to plan her next move, Sinha had to coordinate with Ranjan, who was also looking for an academic position. Ranjan got a job at Boston University and Sinha, while still in California, applied for and received a fellowship from Pioneer Hi-Bred, an agricultural seed company. The fellowship was not tied to working in any specific laboratory, so the family moved to Boston, and Sinha found workspace in a Drosophila geneticist’s lab at Boston University. “I worked on maize and tomato genetics on my own, and that was my postdoc,” Sinha says.

Being an Indian and a woman, I kept thinking ‘What did I do to deserve this faculty position? . . . I came to realize that this is widespread. My smart and capable female students come to me constantly questioning themselves, and it breaks my heart.

In 1995, she accepted an assistant professor position in the plant biology department at UC Davis. Her husband and son stayed in Boston at first. A year later, her son moved to be with her, and in 1997 Ranjan joined his wife and son in California, accepting an assistant professor position in the School of Management at Santa Clara University.

At UC Davis, Sinha focused on a subset of homeobox genes in the tomato plant called the Class I KNOX genes, which encode transcription factors necessary for the proper patterning of plant organs. “The tomato was interesting because it had a compound leaf structure, rather than a simple leaf structure, and I wanted to understand what role these KNOX homeobox genes played in shaping the leaves,” she says. Serendipity was on her side: she had cloned two KNOX homeobox genes while at PGEC and wanted to see if any mapped to known tomato mutants. “The first Southern blot I ever did showed me that one of the genes I cloned mapped to a mutant I had found in UC Davis’s tomato stock center.” That Southern blot ended up in a Plant Molecular Biology paper, published in 1999, in which Sinha and her colleagues identified a novel version of a KNOX homeobox gene in tomato caused by fusion between a KNOX gene and an adjacent metabolic gene.

She also continued to focus on how plant diversity developed throughout evolution, using the leaf as a model. Geeta Bharathan, a postdoctoral fellow in Sinha’s lab at the time, examined the role of homeobox genes in leaf forms from ferns to flowering plants, finding that the origins of simple leaf structures varied and that similar leaf structures don’t necessarily predict homology among plants. “We keep finding that the same genes are important for sculpting morphological diversity in plants,” Sinha says. The results were published in Science in 2002.

Sinha’s lab was also working on parasitic plants, which attach to another plant, siphoning water, nutrients, and RNA from their hosts. Amos Alakonya, a graduate student from Kenya, was interested in the mechanics of plant parasitism because plant parasites, such as Striga, plague maize and sorghum agriculture in Africa. Focusing on a California-native parasite, Alakonya and collaborators showed that small interfering RNAs expressed in the host plant can lead to silencing of genes in the parasitic plant, a phenomenon now called host-induced gene silencing. “It was a Trojan horse approach that Amos came up with,” Sinha says. The lab is now trying to modify this phenomenon to induce resistance to parasitic plants in tomato plants. “These parasites can be devastating, resulting in 60 percent to 70 percent loss of tomato yields,” Sinha says.

An energetic spirit

Despite her success, Sinha says she found it difficult to shake her “imposter syndrome” for a long time. “Being an Indian and a woman, I kept thinking ‘What did I do to deserve this faculty position?’” she says. “I came to realize that this is widespread. My smart and capable female students come to me constantly questioning themselves, and it breaks my heart. Years and years of being at great universities and doing good work, and we are still questioning ourselves.”

Being around young people helps me keep up with their concerns, the increased social responsibilities they are taking on, and also the technology that they are embracing.

Sinha has responded to the lingering doubts she and her trainees experience by embracing her cultural background and respecting diversity in her lab. “My lab has always had an international flavor, and I love that because it’s wonderful to see how international scientists adjust to our culture, and we adjust to theirs.” She recalls, for example, how a postdoc from Japan had to ask her about a phrase a graduate student in the lab used. The postdoc had been in the lab for a month when he told Sinha that he had just made his 40th DNA construct. “A graduate student overheard, did a double take, and said ‘Man, you are an animal in the lab,’” she explains. The postdoc later came to Sinha’s office to ask what the graduate student had meant. “I told him it was a great compliment, it meant that he had amazing hands in the lab,” she says. “When the postdoc was leaving the lab, we got him a shirt that said ‘Japanimal’ that he would then have to explain the meaning of back in Japan.”

Along with the banter and conviviality of those in her lab, Sinha also enjoys the fresh infusion of ideas as she interacts with new students each year. “Being at a university is energizing. You may be getting older, but the people around you are always of the same young age group. Sometimes you look in the mirror and are shocked to see that you are aging because no one around you appears to be aging,” Sinha explains. “Being around young people helps me keep up with their concerns, the increased social responsibilities they are taking on, and also the technology that they are embracing.”

And it gives Sinha an opportunity to share her passion for promoting the importance of plant life. “I always begin the introductory biology class I teach at UC Davis by saying, ‘If we didn’t have plants, none of us would exist,’” she says. “We need to spark young people’s interests in plants.”