PROFILE PROFILE Profile of Natasha V. Raikhel

Leigh Cooper, Science Writer

A plane crash galvanized Natasha Raikhel and her family “Quite frankly, this plane crash was the last drop, and into leaving the for the United States. At the many things became irrelevant and unimportant,” says time, Raikhel was studying invertebrates while living in Raikhel. “We wanted to move to a free society, even if it Leningrad. Raikhel’s husband and son had joined her on meant [starting] everything all over again.” Emigrating a field expedition to gather samples in Baku, Azerbaijan, allowed Raikhel to pursue a career studying the inner and on the return trip, the plane crashed, killing a number workings of plant cells. Elected to the National Academy of passengers. Raikhel’s family survived, but when Rai- of Sciences in 2012, Raikhel has ransacked the scientific khel asked the airline for a statement detailing the loss of toolshed, combining cellular, molecular, and genetic her field equipment, the airline refused to acknowledge methodologies to investigate the transport of molecules that the crash had taken place. After insistent requests, within and between organelles in plant cells. Her findings the airline acquiesced that an “unexpected landing” had may have implications for global food security and bio- occurred and provided 150 rubles for their lost luggage. 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— 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 was incredibly difficult for me to digest and figure out how to move forward,” says Raikhel. “However, I be- came very disciplined as a child, because I had to play like six to seven hours a day.” She adds that playing the piano developed her creativity, because “when you play music, you are always trying to figure out how to express yourself better and you learn how to listen.” Raikhel channeled her energy toward biology and attended Leningrad State University, where she and four male students, including her future husband Alexander Raikhel, were recruited into the inverte- brate department. Raikhel went on to earn a Master’s degree for her investigation of ciliate conjugation, a process in which ciliates couple together and ex- change micronuclei. She focused on the mitosis and meiosis of ciliate micronuclei and macronuclei. “It was observational and descriptive: electron micros- copy and light microscopy. At that time that was state of the art,” says Raikhel. Upon obtaining her Master’s degree, Raikhel hoped to continue her studies, but graduate programs at the time accepted only a certain number of Jews into each doctoral cohort. Instead, the government assigned Raikhel and her husband jobs in Vladivostok, Natasha Raikhel. Image courtesy of Natasha V. Raikhel. 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.

1672–1674 | PNAS | February 20, 2018 | vol. 115 | no. 8 www.pnas.org/cgi/doi/10.1073/pnas.1721892115 Downloaded by guest on September 28, 2021 Union, unless you were posted in Leningrad, Moscow, or perhaps Novosibirsk, there was no scientific future,” says Raikhel. “No matter how they tried to entice us or threaten us, we said we would not sign the distribution papers.” Finally, Raikhel and her husband were given jobs in Leningrad. Raikhel’s day job was in a water-treatment center, and on nights and weekends the newlyweds pursued their doctoral studies. After 2 years, Raikhel became a technician in the laboratory of her advisor, Yuri Poljansky, at the Institute of Cytology of the Russian Academy of Sciences. In 1975 she earned her doctorate, a continuation of her work on ciliate con- jugation, and the Russian Academy offered her an assistant professorship.

Immigrating to the United States After the plane crash in 1978, continued encounters with anti-Semitism, and the death of her father, Rai- khel and her family decided to leave Russia. “I had always wanted to leave,” says Raikhel. “Even if I was sweeping the streets of New York, I was going to im- migrate and that was the end of it.” Natasha Raikhel and her first son, Eugene, the year before moving from the Soviet Union to Athens, . Image courtesy of Natasha V. Raikhel. Raikhel and her family chose to move to Athens, Georgia because Raikhel knew zoologist Jerome Paulin, who secured a half-time Raikhel found that one section of the lectin protein, postdoctoral position for Raikhel in his laboratory as called the C terminal because of its carboxyl group, well as a postdoctoral position for her husband. After was acting as the lectin’s passport into the vacuole, arriving in Georgia in 1979, Raikhel says that the rel- a multifunctional organelle essential for plant cell atively slow pace of life in the American South allowed growth and development (2). “It is [like a] lock and her family to ease into life in America more comfort- keys. You have to have them in the right order to come ably than may have been possible in a large city, such to the correct place,” says Raikhel. as New York. However, she and her family missed the Raikhel and her colleagues found that a barley high culture and excitement of city life in Leningrad. lectin lacking a C-terminal propeptide was secreted ’ Her ciliate work in Paulin s laboratory provided outside the cell instead of being directed to the vac- “ Raikhel with a connection to her former life. I did the uole, and incorporating the C-terminal propeptide ” “ same type of work I did before, says Raikhel. But, into an unrelated protein led to that protein being since I could do it in my sleep, it was boring. I realized I shuttled into the vacuole. Concurrently, studies by didn’t immigrate to do the same thing.” Raikhel took other scientists had found that some N-terminal pro- advantage of an opportunity to move to Barry Palevitz’s peptides, marked by their amine groups, could also plant cell biology laboratory, where she worked with funnel proteins to vacuoles. “From the moment we graduate student Michael Mishkind. and others found these [C- and N-terminal] targeting Together, the duo delved into lectins, proteins that signals, I became the trafficking woman,” says Raikhel, bind to sugars. They focused on wheat germ agglutinin. describing her research niche as “organelle traffick- “We wanted to understand its distribution in plants,” ing.” Continuing with a laugh, she adds, “I always says Raikhel. “And we wanted to know what it does in ’ ” plants.” They found that the embryos of many grasses have to say I m not trafficking drugs. expressed wheat germ agglutinin-like lectins in differ- In 1998, doctors handed Raikhel a diagnosis of breast ent cellular layers of the coleoptile, a protective sheath cancer. Despite months of chemotherapy and radiation, on the shoot tip (1). For example, wheat expresses Raikhel says that she continuously dragged herself to her lectin in the coleoptile’s outer layer, whereas rye con- laboratory, finding strength in her work and her students. tains lectin in both the inner and outer layers of the By 2000, she was in recovery and was asked to accept the coleoptile. This variability opened up questions about role of editor-in-chief at Plant Physiology.Raikhelem- the regulation of lectin in plants and the evolution of braced the new challenge and served as the first and, to these proteins in agricultural species, says Raikhel. date, only female editor-in-chief of the 91-year-old journal.

Trafficking in Plant Cells Building an Institute In 1986, Raikhel accepted an offer of an assistant By 2001 Raikhel and her husband were in search of professorship at Michigan State University’s Plant Re- new challenges. After moving to the University of search Laboratory, and her family, which now included California, Riverside, Raikhel became the founding her second son, moved to East Lansing. She contin- director of the Center for Plant Cell Biology (CEPCEB). ued studying wheat germ agglutinin, but a discovery “I wanted to build something that everybody at Uni- about barley lectin helped Raikhel focus her research. versity of California, Riverside would benefit [from],

Cooper PNAS | February 20, 2018 | vol. 115 | no. 8 | 1673 Downloaded by guest on September 28, 2021 (4). Two of these compounds altered protein delivery in Arabidopsis. Another early screen of 2,016 chem- icals pinpointed a molecule that affected the transport of vesicles in Arabidopsis seedlings (5). Expanding those efforts, Raikhel developed an au- tomated screen of more than 46,000 chemicals and identified 360 chemicals that inhibited pollen gen- eration in Arabidopsis; 123 of those chemicals al- tered the development of Arabidopsis root tips (6). Next, Raikhel and her colleagues developed another screen that identified a molecule that binds to a protein complex involved in vesicle trafficking, a process that inhibited the exchange of material across cellular membranes in both plant and human cells (7). “The small molecules allowed us to bypass both the problem of redundancy and lethality,” said Raikhel. “We could increase or decrease the con- centration of the chemicals, making the phenotype conditional in a way, with the added ability to wash Natasha Raikhel (Left) and postdoctorate Wilhelmina Van De Ven (Right). Image ” courtesy of Natasha V. Raikhel. out the chemical and reverse the phenotype.

Immigrant to Advocate but I wanted to concentrate on plants because that Now retired and living in Pasadena, California, ” is where I could make a difference, Raikhel says. Raikhel’s newest projects harken back to her life in the Raikhel says she is especially proud that four CEPCEB Soviet Union. Raikhel has organized art exhibits and women were members of the National Academy of concerts at various European and Chinese scientific Sciences by the end of her tenure. conferences. “Music and art help me deal with my Raikhel continued her research on organelle traf- personal problems,” says Raikhel. “I want to share it ficking, and her Inaugural Article (3) demonstrates how with young people who may have never been to a ribosomal proteins modulate auxin, a plant hormone museum or heard live music.” that regulates cargo destined for vacuoles. But she At the same time, Raikhel is working with a number also delved into chemical genomics. At Michigan of universities and institutions in China to mentor fe- State, Raikhel learned that plants contain many re- male scientists. “I share with them my story and am dundancies in their genetic code. “It is protection,” trying to encourage them to embrace female scien- said Raikhel. “If I eliminate one gene in order to ’ ” survive, another one will come to help.” Many traf- tists leadership, said Raikhel. ficking genes are essential for development, so mutants Raikhel points to the contributions she and her with an eliminated trafficking gene often fail to grow. family have made to the scientific community in the These obstacles limited Raikhel’s ability to map regula- United States since emigrating from Russia. Raikhel tory pathways for trafficking, so she developed chemical says that the United States should support the best screens to test whether any of thousands of chemicals scientists, both Americans and immigrants, because cause a plant to display a specific phenotype. “That was America benefits tremendously when science and a rather new thing I started at CEPCEB,” said Raikhel. technology flourish. “Look at history. How many “Now a lot of plant biologists all over the world are using Nobel Laureates are immigrants? Look at the National chemical screens for their particular research in plants.” Academy. How many are immigrants?” says Raikhel. Raikhel started small with a screen of 4,800 chem- “The United States cannot slow down being a front icals, identifying 14 compounds that stimulated yeast row country in science and technology. We can’tbe to secrete a protein usually associated with vacuoles 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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