PROFILE Profile of Angelika Amon, winner of the 2019 Vilcek Prize in Biomedical Science PROFILE Jan Vilceka and Prashant Nairb,1 In 2006, the New York City-based Vilcek Foundation launched a prize program to honor US-based bio- medical scientists who immigrated to the United States and made extraordinary contributions to their fields (1). Established in 2000 by Jan and Marica Vilcek, the Vilcek Foundation has been supported by Jan Vilcek’s donation of royalties received from the New York Univer- sity School of Medicine for his contribution to the devel- opment of the antiinflammatory drug infliximab. The Vilcek Foundation’s prize program was born out of the Vilceks’ desire to recognize the contributions of immi- grants to science and arts in the United States. It is also a celebration and emblem of immigration’s role in secur- ing the primacy of the United States in science and arts on the world stage. There is no other major prize that specifically recognizes immigrant contributions to science in the United States. Since the establishment of the prize program in 2006, Angelika Amon. Image courtesy of Samara Vise (Koch Institute for Integrative Cancer 15 scientists have received the Vilcek Prize in Biomedical Research, Cambridge, MA). Science. The Vilcek Foundation also recognizes outstand- ing young foreign-born scientists through the establish- has brought to light principal players in the balletic ment of Prizes for Creative Promise in Biomedical Science; process by which cells bequeath genetic material to these prizes are open to candidates who are not more than offspring. Along the way, her work has revealed how 38 y old at the time of consideration. To date, 22 scientists missteps in the process result in outcomes such as have received Prizes for Creative Promise in Biomedical cancer. For her crystalline insights into life’s elemental Science (in parallel, the Vilcek Foundation also awards an equal number of prizes in the arts to outstanding problems, the scientific community has heaped plaudits foreign-born artists active in the United States) (2). on Amon, including memberships in the National Acad- The recipient of the 2019 Vilcek Prize in Biomedical emy of Sciences, the American Academy of Arts and Science is Angelika Amon, an Austrian-born molecular and Sciences, and the European Molecular Biology Organi- cell biologist at the Massachusetts Institute of Technology. zation; a Breakthrough Prize in life sciences; a National Academy of Sciences molecular biology award; and a Solving the Puzzle of Cell Division: Angelika Howard Hughes Medical Institute Investigator award. Amon Angelika Amon’s passion for biology began early, Moving Picture when a picture of dividing plant cells viewed through a Amon was born and raised in Vienna, Austria. Her passion microscope sparked an enduring fascination with life’s for cell biology was sparked in middle school, when a grand mysteries. Over the course of a career spanning teacher showed the class time-lapse images of di- nearly three decades, Amon, a professor of cancer viding plant cells. As she thrilled to the sight of the research at Massachusetts Institute of Technology and cells sharing chromosomes in a ritualized sequence, winner of the 2019 Vilcek Prize in Biomedical Science, the riveting images seized her imagination and aDepartment of Microbiology, New York University School of Medicine, NYU Langone Medical Center, New York, NY 10016; and bProceedings of the National Academy of Sciences USA, Washington, DC 20418 Author contributions: J.V. and P.N. wrote the paper. Conflict of interest statement: J.V. is the president and cofounder of the Vilcek Foundation, whose mission is to raise awareness of immigrant contributions to the United States. P.N. has received remuneration for promotional work for the Vilcek Foundation. Published under the PNAS license. 1To whom correspondence should be addressed. Email: [email protected]. Published online March 18, 2019. www.pnas.org/cgi/doi/10.1073/pnas.1903221116 PNAS | April 9, 2019 | vol. 116 | no. 15 | 7157–7159 Downloaded by guest on September 29, 2021 were seared into her memory. “They were amazing cells progress through the cell cycle and partition their black-and-white movies from the sixties, long before chromosomes. Over time, those efforts ossified her fluorescence microscopy and the fancy techniques we standing among the world’s leading geneticists and use today. Plant cells have these large chromosomes, landed her a faculty job at the Koch Institute for In- and I just loved seeing the cells divide,” she recalls. tegrative Cancer Research at the Massachusetts Institute Amon channeled her youthful fascination into un- of Technology, where she has since stayed. From her dergraduate studies in biology at the University of perch at the institute, Amon has vastly expanded re- Vienna. In 1989, she enrolled in a doctoral program at searchers’ understanding of aspects of cell division the Institute of Molecular Pathology, joining the lab- intricately tied to human disease. oratory of a new arrival at the institute, the Englishman Chief among those findings is the role of an en- Kim Nasmyth, who had earned an international repu- zyme called Cdc14 in inducing cells to exit from mi- tation as a first-rate geneticist. Nasmyth was quick to tosis. The final stage in the cell cycle, exit from mitosis spot his protege’s promise and armed her with practical marks a period in the life of dividing cells when the skills in the genetics of yeast, a model organism favored cellular apparatus that partitions chromosomes be- by cell biologists. tween daughter cells is dismantled, the envelopes Amon’s research in Nasmyth’s laboratory was no surrounding the daughter nuclei are rebuilt, and the mere finger-exercise for the full-scale work on yeast contents of the daughter cells are pulled apart and genetics she later undertook. Besides sharpening her packaged. Previously, Amon had demonstrated that instincts, her doctoral studies led to major discoveries cyclins must be degraded before cells can exit from on the cell cycle. A byzantine process by which cells mitosis. Building on that work, Amon found that cyclin duplicate their contents and divide, the cell cycle breakdown is promoted by a pair of proteins, Cdc20 progresses in well-defined stages: G1 (gap1), S (syn- and Cdh1, that activate the cyclin-degrading machin- thesis), G2 (gap2), and M (mitosis); the gaps allow cells ery, dubbed the anaphase-promoting complex (4). time to grow and duplicate organelles before division. Peeling back the layers of a magnificently textured The cell cycle is controlled by a staggering web of web of signals, she next showed that the enzyme interlinked signals. Among these signals are the aptly Cdc14 triggers exit from mitosis (5). “It turns out that named cyclins, proteins that accumulate within cells as Cdc14 essentially resets cells for the next stage of they enter mitosis. Amon’s work revealed that cyclins the cell cycle by acting on Cdh1 and activating cyclin must be broken down before cells make the passage breakdown,” explains Amon. In turn, Cdc14, she found, from mitosis to G1. Cyclin breakdown, she found, is regulated by an assorted crew of proteins collectively continues throughout G1 and ceases as cells enter the called the mitotic exit network (6). next stage, the S phase, when DNA is duplicated. Having established the primacy of the mitotic exit “What this work really established is the logic of the signaling network in cell division, Amon sought to cell cycle, how one stage sets up the next,” she explains. uncover signals at the heart of the network. One such Published in Cell, the findings marked an overture to signal turned out to be the physical position of the a career rich in elegant reports on the elaborately or- nucleus. A natural mechanism in dividing cells ensures chestrated symphony of cell division (3). that they postpone exit from mitosis until the nuclei are correctly partitioned between daughter cells; the Ascent to Success alternative would result in cellular mayhem. “You Armed with a doctoral degree, Amon next braved a would end up with a cell that has two nuclei and one foray into fruit fly research during a brief postdoctoral that has none,” explains Amon. Amon found that the stint with developmental biologist Ruth Lehmann at activation of Cdc14, as well as exit from mitosis, is the Whitehead Institute for Biomedical Research in stalled until a pair of interacting proteins called Tem1 Cambridge, Massachusetts. In 1994, as she left the and Lte1 assume their position in the nascent bud of comforts of her native Austria for the chance to per- budding yeast cells. The Tem1/Lte1 duo, it turns out, form research in the United States, the move marked a cohabit the bud only after the nucleus, freshly minted departure in more than one sense. Amon had become in the mother cell, has slipped through the slender adept at working with yeast, a model organism then bud neck into the bud. Together, this and other sig- deemed far easier to manipulate for molecular genetic nals, asymmetrically arrayed between the mother cell studies than fruit flies, which proved a daunting and bud, ensure that cell division results in cells with prospect before the advent of such handy tools as the correct genetic complement. These acutely observed CRISPR. “Ruth was an amazing role model and men- insights revealed how molecular asymmetry ironically tor, and I learned so much from her. But I soon found underpins the wondrous symmetry of cell division (7). out that I didn’t like working with flies. Back then, once you had worked with yeast, you were spoiled; the only Peril in Numbers rate-limiting step in working with yeast was your Because cell division is a life-sustaining process, Amon’s brain,” she says.