obituary Angelika Amon (1967–2020)

n 29 October 2020, Massachusetts expression in aneuploid cells was mostly Institute of Technology (MIT) proportional to chromosome number, Obiologist Angelika Amon leading to gene expression imbalance, passed away at the age of 53 after a abnormal protein complex assembly, and two-and-a-half-year battle with ovarian proteotoxic stress. Her subsequent studies cancer. lost a brilliant scientist, confirmed these findings in mammalian and the community lost a vibrant and cells and demonstrated that extensive highly original voice. -induced expression imbalance Angelika grew up in , , the compromises DNA replication and repair, oldest of four children. At an early age, she generating additional genome instability was captivated by science and developed a and mutagenesis. fascination with This clear demonstration of the after viewing a classic cell division video. deleterious impact of aneuploidy on cell She pursued this in earnest as a graduate growth still left the field with a paradox: student with at the Institute why are the vast majority of rapidly dividing of Molecular Pathology in Vienna, where cancer cells aneuploid? Part of the answer is she made several major discoveries. These that cells can acquire aneuploidy-tolerating included advances on the regulation of mutations, some of which Angelika’s group -dependent kinase, an understanding identified. Additionally, aneuploidy-induced of the transcriptional feedback circuits that instability may drive the acquisition of control cyclin expression, and the discovery Credit: Image courtesy of Theresa Weis other tumour-promoting mutations. that mitotic cyclin proteolysis promotes Finally, as shown by Angelika and others, irreversible mitotic exit. I am still struck by aneuploidy can itself promote growth and the elegance of these early papers, whose proper chromosome segregation. Although tumourigenesis in certain contexts. With precision and rigor carried over into all of the MEN pathway is unique to budding much thanks to Angelika, we now think of Angelika’s later work on , , , this work highlighted universal aneuploidy as a large-effect mutation, which, and aneuploidy. themes: the centrosome’s role as a signalling although usually deleterious, can sometimes Angelika did a brief postdoctoral hub, spatial regulation of signalling increase fitness and drive proliferation. fellowship in Drosophila genetics with molecules, and feedback mechanisms to Angelika was highly celebrated for at the drive irreversible cell cycle transitions. these seminal discoveries. She was the at MIT before reverting to type and In addition to these discoveries Kathleen and Curtis Marble Professor of rekindling her passion for the yeast cell on mitotic chromosome segregation, Cancer Research at the Koch Institute at cycle. As a Whitehead Fellow, and later Angelika’s group made many important the Massachusetts Institute of Technology as a MIT faculty member, she got off to a contributions toward understanding how and an Investigator of the Howard Hughes fast start: she discovered substrate-specific this machinery is adapted for meiotic Medical Institute. She received numerous activators of the E3 ubiquitin ligase that chromosome segregation. awards, most recently the Breakthrough drive onset and mitotic exit In recent years, Angelika focused on the and Vilcek prizes. She was a member of the (the anaphase-promoting complex). With consequences of aneuploidy, the presence US National Academy of Sciences and a Andrew Murray, she showed that one of of an abnormal number of chromosomes in fellow of the American Academy of Arts these activators, Cdc20, was the target of the a cell, which causes human genetic disease and Sciences. spindle assembly checkpoint. and is common in cancer. Since the dawn of If many scientific leaders have large Angelika’s laboratory then led the way the modern era of biology, it was appreciated personalities, Angelika’s was outsized in deciphering the intricate signalling that aneuploidy generates pathological squared! She was funny, boisterous, and network that controls the exit from phenotypes, and these observations became sharp. She did not do circumlocution but in budding yeast (the mitotic exit network lynchpins for the chromosome theory went right for the point. At conferences, or MEN pathway and the related pathway of inheritance. Nevertheless, the cellular her incisive questions, usually fired from she dubbed “FEAR”). She co-identified the consequences of aneuploidy, particularly the back of the auditorium, could be protein phosphatase Cdc14 as the central whether all induce a intimidating. She was the life of any party downstream effector of the pathway and common set of physiological alterations, or conference, regaling her audience showed that MEN signalling activates remained unclear. with stories of all her latest passions and Cdc14 by liberating it from the nucleolus. Angelika had the insight to use yeast obsessions, be it American football, Candy She and others showed that the MEN genetics to systematically dissect this Crush, People Magazine, or her 23andMe cascade is initiated when the mitotic spindle problem. In a landmark 2007 paper, her report. I vividly recall a skeet shooting enters the new daughter cell, bringing a group constructed a near-complete series outing that Angelika organised during centrosome-bound G protein in contact with of haploid yeast strains containing extra a Federation of American Societies for its activator on the daughter-cell cortex. This copies of individual chromosomes. Analysis Experimental Biology meeting. Scientists elegantly explains how a cell can sense the of these strains showed that aneuploidy are generally not experienced or handy with position of its mitotic spindle and enforce was deleterious, slowing cell proliferation shotguns, but Angelika was a natural talent. a ‘spindle position checkpoint’, ensuring due to a G1 cell cycle delay. Gene I cannot forget the look of predatory joy that

Nature Cell Biology | VOL 23 | January 2021 | 1–2 | www.nature.com/naturecellbiology 1 obituary came with each clay pigeon Angelika blew Although far too short, Angelika Amon’s also help me better appreciate the other out of the Georgia sky—the very same look life was full. Her scientific career is an colleagues, students, and friends who she had when, as a starting Fellow, her film inspiration for its impact and originality. enrich my own journey through science came off the X-Omat showing that Cdh1 She was a wonderful mentor, and many and through life, as Angelika did. triggered cyclin degradation. of her trainees are now leaders in their Hopefully this small indulgence in a shared Angelika had charming small vices and fields. She was a role model for many transgression will remind me to live eccentricities. She lived on Diet Coke women in science. In addition to her my own life on the larger scale, with the and lugged a couple of six packs to each professional accomplishments, she married same passion and purpose that Angelika scientific conference lest God forbid the her high school sweetheart, dearly loved brought to hers. ❐ hotel ran out. Before she quit, she smoked her two daughters, and had a rich family cigarettes with the same gusto that she had life. She reminds us that professional David Pellman ✉ for everything else. As a postdoc, I indulged accomplishment does not preclude personal Dana-Farber Cancer Institute, Harvard Medical in many cigarettes with her sitting on the warmth or a fulfilling private life. School, Howard Hughes Medical Institute, Boston, front steps of the Whitehead Institute, My family recently got me to swear MA, USA. talking science, getting instruction on off Diet Coke, but now I think I’ll go ✉e-mail: [email protected] how to best organise my personal life, back. An occasional can will not harm me, and watching the clouds roll over the and I am going to raise a defiant toast to Published online: 8 January 2021 Kendall Square cityscape. Angelika. Perhaps the quiet moment will https://doi.org/10.1038/s41556-020-00612-7

2 Nature Cell Biology | VOL 23 | January 2021 | 1–2 | www.nature.com/naturecellbiology