PROFILE

Profile of Natasha V. Raikhel PROFILE

Leigh Cooper, Science Writer

A plane crash galvanized Natasha Raikhel and her family into leaving the for the United States. At the time, Raikhel was studying invertebrates while living in Leningrad. Raikhel’s husband and son had joined her on a field expedition to gather samples in Baku, Azerbaijan, and on the return trip, the plane crashed, killing a number of passengers. Raikhel’s fam- ily survived, but when Raikhel asked the airline for a statement detailing the loss of her field equipment, the airline refused to acknowledge that the crash had taken place. After insistent requests, the airline acquiesced that an “unexpected landing” had oc- curred and provided 150 rubles for their lost luggage. “Quite frankly, this plane crash was the last drop, and many things became irrelevant and unimportant,” says Raikhel. “We wanted to move to a free society, even if it meant [starting] everything all over again.” Emigrating allowed Raikhel to pursue a career studying the inner workings of plant cells. Elected to the National Academy of Sciences in 2012, Raikhel has ransacked the scientific toolshed, combining cellular, molecular, and genetic methodologies to investigate the transport of molecules within and between organelles in plant cells. Her findings may have implications for global food security and bio- fuel production in the 21st century.

Piano Bench to Laboratory Bench As a child, Raikhel had no desire to become a scientist. Instead, she spent hours each day practicing the pi- ano. Raikhel attended a music school in Leningrad— Natasha Raikhel. Image courtesy of Natasha V. Raikhel. now —until, at the end of high school, one of the teachers suggested that she may not have the necessary talent to excel at piano. “This degree for her investigation of ciliate conjugation, a was incredibly difficult for me to digest and figure out process in which ciliates couple together and ex- how to move forward,” says Raikhel. “However, I be- change micronuclei. She focused on the mitosis and came very disciplined as a child, because I had to play meiosis of ciliate micronuclei and macronuclei. “It like six to seven hours a day.” She adds that playing was observational and descriptive: electron micros- the piano developed her creativity, because “when copy and light microscopy. At that time that was state you play music, you are always trying to figure out how of the art,” says Raikhel. to express yourself better and you learn how to listen.” Upon obtaining her Master’s degree, Raikhel Raikhel channeled her energy toward biology and hoped to continue her studies, but graduate programs attended Leningrad State University, where she and at the time accepted only a certain number of Jews four male students, including her future husband into each doctoral cohort. Instead, the government Alexander Raikhel, were recruited into the inverte- assigned Raikhel and her husband jobs in Vladivostok, brate department. Raikhel went on to earn a Master’s near Russia’s border with North Korea. “In the Soviet

Published under the PNAS license. This is a Profile of a member of the National Academy of Sciences to accompany the member’s Inaugural Article, on page 19537 in issue 48 of volume 109. This Profile is based on an interview with N.V.R. conducted in July 2017. N.V.R. agreed to become Interim Editor-in-Chief of PNAS in December 2017.

www.pnas.org/cgi/doi/10.1073/pnas.1721892115 PNAS Latest Articles | 1of3 Downloaded by guest on September 24, 2021 didn’t immigrate to do the same thing.” Raikhel took advantage of an opportunity to move to Barry Palevitz’s plant cell biology laboratory, where she worked with graduate student Michael Mishkind. Together, the duo delved into lectins, proteins that bind to sugars. They focused on wheat germ agglutinin. “We wanted to understand its distribution in plants,” says Raikhel. “And we wanted to know what it does in plants.” They found that the embryos of many grasses expressed wheat germ agglutinin-like lectins in differ- ent cellular layers of the coleoptile, a protective sheath on the shoot tip (1). For example, wheat expresses lectin in the coleoptile’s outer layer, whereas rye con- tains lectin in both the inner and outer layers of the coleoptile. This variability opened up questions about the regulation of lectin in plants and the evolution of these proteins in agricultural species, says Raikhel.

Trafficking in Plant Cells In 1986, Raikhel accepted an offer of an assistant professorship at Michigan State University’s Plant Re- Natasha Raikhel and her first son, Eugene, the year before moving from the Soviet search Laboratory, and her family, which now included Union to Athens, . Image courtesy of Natasha V. Raikhel. her second son, moved to East Lansing. She contin- ued studying wheat germ agglutinin, but a discovery Union,unlessyouwerepostedinLeningrad,Moscow,or about barley lectin helped Raikhel focus her research. perhaps Novosibirsk, there was no scientific future,” says Raikhel found that one section of the lectin protein, Raikhel. “No matter how they tried to entice us or threaten called the C terminal because of its carboxyl group, us, we said we would not sign the distribution papers.” was acting as the lectin’s passport into the vacuole, Finally, Raikhel and her husband were given jobs in a multifunctional organelle essential for plant cell Leningrad. Raikhel’s day job was in a water-treatment growth and development (2). “It is [like a] lock and center, and on nights and weekends the newlyweds keys. You have to have them in the right order to come ” pursued their doctoral studies. After 2 years, Raikhel to the correct place, says Raikhel. became a technician in the laboratory of her advisor, Raikhel and her colleagues found that a barley Yuri Poljansky, at the Institute of Cytology of the lectin lacking a C-terminal propeptide was secreted Russian Academy of Sciences. In 1975 she earned her outside the cell instead of being directed to the vac- doctorate, a continuation of her work on ciliate con- uole, and incorporating the C-terminal propeptide jugation, and the Russian Academy offered her an into an unrelated protein led to that protein being shuttled into the vacuole. Concurrently, studies by assistant professorship. other scientists had found that some N-terminal pro- Immigrating to the United States peptides, marked by their amine groups, could also funnel proteins to vacuoles. “From the moment we After the plane crash in 1978, continued encounters and others found these [C- and N-terminal] targeting with anti-Semitism, and the death of her father, Rai- signals, I became the trafficking woman,” says Raikhel, khel and her family decided to leave Russia. “I had describing her research niche as “organelle traffick- always wanted to leave,” says Raikhel. “Even if I was ing.” Continuing with a laugh, she adds, “I always sweeping the streets of New York, I was going to im- have to say I’m not trafficking drugs.” migrate and that was the end of it.” In 1998, doctors handed Raikhel a diagnosis of breast Raikhel and her family chose to move to Athens, cancer. Despite months of chemotherapy and radiation, Georgia because Raikhel knew Raikhel says that she continuously dragged herself to her zoologist Jerome Paulin, who secured a half-time laboratory, finding strength in her work and her students. postdoctoral position for Raikhel in his laboratory as By 2000, she was in recovery and was asked to accept the well as a postdoctoral position for her husband. After role of editor-in-chief at Plant Physiology. Raikhel em- arriving in Georgia in 1979, Raikhel says that the rel- braced the new challenge and served as the first and, to atively slow pace of life in the American South allowed date, only female editor-in-chief of the 91-year-old journal. her family to ease into life in America more comfort- ably than may have been possible in a large city, such Building an Institute as New York. However, she and her family missed the By 2001 Raikhel and her husband were in search of high culture and excitement of city life in Leningrad. new challenges. After moving to the University of Her ciliate work in Paulin’s laboratory provided California, Riverside, Raikhel became the founding Raikhel with a connection to her former life. “I did the director of the Center for Plant Cell Biology (CEPCEB). same type of work I did before,” says Raikhel. “But, “I wanted to build something that everybody at Uni- since I could do it in my sleep, it was boring. I realized I versity of California, Riverside would benefit [from],

2of3 | www.pnas.org/cgi/doi/10.1073/pnas.1721892115 Cooper Downloaded by guest on September 24, 2021 but I wanted to concentrate on plants because that is where I could make a difference,” Raikhel says. Raikhel says she is especially proud that four CEPCEB women were members of the National Academy of Sciences by the end of her tenure. Raikhel continued her research on organelle traf- ficking, and her Inaugural Article (3) demonstrates how ribosomal proteins modulate auxin, a plant hormone that regulates cargo destined for vacuoles. But she also delved into chemical genomics. At Michigan State, Raikhel learned that plants contain many re- dundancies in their genetic code. “It is protection,” said Raikhel. “If I eliminate one gene in order to survive, another one will come to help.” Many traf- ficking genes are essential for development, so mutants with an eliminated trafficking gene often fail to grow. These obstacles limited Raikhel’s ability to map regula- tory pathways for trafficking, so she developed chemical screens to test whether any of thousands of chemicals Natasha Raikhel (Left) and postdoctorate Wilhelmina Van De Ven (Right). Image cause a plant to display a specific phenotype. “That was courtesy of Natasha V. Raikhel. a rather new thing I started at CEPCEB,” said Raikhel. “ Now a lot of plant biologists all over the world are using Immigrant to Advocate ” chemical screens for their particular research in plants. Now retired and living in Pasadena, California, Raikhel started small with a screen of 4,800 chem- Raikhel’s newest projects harken back to her life in the icals, identifying 14 compounds that stimulated yeast Soviet Union. Raikhel has organized art exhibits and to secrete a protein usually associated with vacuoles concerts at various European and Chinese scientific (4). Two of these compounds altered protein delivery conferences. “Music and art help me deal with my in Arabidopsis. Another early screen of 2,016 chem- personal problems,” says Raikhel. “I want to share it icals pinpointed a molecule that affected the transport with young people who may have never been to a of vesicles in Arabidopsis seedlings (5). museum or heard live music.” Expanding those efforts, Raikhel developed an au- At the same time, Raikhel is working with a number tomated screen of more than 46,000 chemicals and of universities and institutions in China to mentor fe- “ identified 360 chemicals that inhibited pollen gen- male scientists. I share with them my story and am eration in Arabidopsis; 123 of those chemicals al- trying to encourage them to embrace female scien- ’ ” tered the development of Arabidopsis root tips (6). tists leadership, said Raikhel. Raikhel points to the contributions she and her Next, Raikhel and her colleagues developed another family have made to the scientific community in the screen that identified a molecule that binds to a United States since emigrating from Russia. Raikhel protein complex involved in vesicle trafficking, a says that the United States should support the best process that inhibited the exchange of material scientists, both Americans and immigrants, because across cellular membranes in both plant and human America benefits tremendously when science and “ cells (7). The small molecules allowed us to bypass technology flourish. “Look at history. How many ” both the problem of redundancy and lethality, said Nobel Laureates are immigrants? Look at the National Raikhel. “We could increase or decrease the con- Academy. How many are immigrants?” says Raikhel. centration of the chemicals, making the phenotype “The United States cannot slow down being a front conditional in a way, with the added ability to wash row country in science and technology. We can’tbe out the chemical and reverse the phenotype.” living in a bubble. We have to embrace everybody.”

1 Mishkind ML, Palevitz BA, Raikhel NV, Keegstra K (1983) Localization of wheat germ agglutinin—Like lectins in various species of the gramineae. Science 220:1290–1292. 2 Bednarek SY, Raikhel NV (1991) The barley lectin carboxyl-terminal propeptide is a vacuolar protein sorting determinant in plants. Plant Cell 3:1195–1206. 3 Rosado A, Li R, van de Ven W, Hsu E, Raikhel NV (2012) Arabidopsis ribosomal proteins control developmental programs through translational regulation of auxin response factors. Proc Natl Acad Sci USA 109:19537–19544. 4 Zouhar J, Hicks GR, Raikhel NV (2004) Sorting inhibitors (Sortins): Chemical compounds to study vacuolar sorting in Arabidopsis. Proc Natl Acad Sci USA 101:9497–9501. 5 Robert S, et al. (2008) Endosidin1 defines a compartment involved in endocytosis of the brassinosteroid receptor BRI1 and the auxin transporters PIN2 and AUX1. Proc Natl Acad Sci USA 105:8464–8469. 6 Drakakaki G, et al. (2011) Clusters of bioactive compounds target dynamic endomembrane networks in vivo. Proc Natl Acad Sci USA 108:17850–17855. 7 Zhang C, et al. (2016) Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis. Proc Natl Acad Sci USA 113:E41–E50.

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