Cobbe, Neville

Di Cara, Francesca

Spradling, Allan C.

Vass, Sharron

Edinburgh Napier Research Repository

IN MEMORIAMMargarete Heck (1959–2023): Cell biologist,geneticist, and incandescent social sparkNeville Cobbe1, Francesca Di Cara2, Allan C. Spradling3, and Sharron Vass4Margarete M.S. Heck, professor of cell biology and genetics,University of Edinburgh, died peacefully at home amid herloving family under a bluemoon on August 30, 2023, after a longjourney with ovarian cancer.Margarete was born in Munich, Germany, on May 5, 1959, toIrina (1928–1980) and Dr. Heinz Hartmann Heck (1927–2002).She came from a renowned family of zoologists: her great-grandfather and grandfather were directors of the Berlin Zoo,while her uncle was the director of the Tierpark Hellabrunn inMunich. Margarete was 6 weeks old when her parents moved toNew York State to live on the grounds of the Catskill Game Farm,the largest private U.S. zoo, where her father became director.She and her younger brother, Georg (1966–2018), enjoyed thezoo and the surrounding forests as their playground, laying thefoundations for her enduring passion for biology.Margarete attended the State University of New York (SUNY)Plattsburgh, where she initially studied medical technology butsubsequently changed her major to microbiology, in which she ex-celled. In 1981, during her senior year, Margarete became the firststudent from SUNY Plattsburgh to be awarded a Fulbright scholar-ship, enabling her to spend a year using electronmicroscopy to studychromatin organization in Chironomus with Dr. Jan-Erik Edström atthe European Molecular Biology Laboratory in Heidelberg.While there, she decided to pursue a PhD in cell biology. Shecompleted her graduate studies at Johns Hopkins University inBaltimore, working with Prof. Bill Earnshaw on the role of DNAtopoisomerase II in chromosome structure and cell proliferation,and generating several highly cited publications (Earnshawet al., 1985; Earnshaw and Heck, 1985; Heck et al., 1988; Heckand Earnshaw, 1986). Margarete and Bill subsequently weremarried at the Catskill Game Farm in 1988. Margarete wasawarded a fellowship from the Jane Coffin Childs MemorialFund for Medical Research to perform postdoctoral research atthe Carnegie Institution for Science, Baltimore, where sheworked with Allan Spradling from 1988 to 1992.Margarete thrived at Carnegie. In a technical tour de force,she used 2D gel analysis coupled with microdissection to map anorigin of DNA replication for the first time in an animal chro-mosome (Heck and Spradling, 1990). Driven by the pressingneed to mutate and identify genes important for myriad cellularprocesses, she joined a 17-person team in the Spradling lab tocarry out a powerful new type of Drosophila genetic screen,single transposon insertional mutagenesis, on the largest scaleyet attempted. Margarete was one of the underbosses who, overan intense 4 months, helped dole out work assignments withcharacteristic kindness and humor, keeping everyone at a highlevel of enthusiasm. The resulting mutant collection jump-started her own research program on chromosome behaviorduring mitosis (Heck et al., 1993). Furthermore, she and theother screen workers generously donated all 1,000+ lethal mu-tations from the screen to the Drosophila Stock Center for freeand immediate public distribution. The collegial nature ofthe Drosophila community was something Margarete enjoyedthroughout her career, and she greatly valued helping tomaintain that tradition.Margarete established her own independent research lab asan assistant professor in the Department of Cell Biology andMargarete Heck in academic regalia, University of Edinburgh, 2009. Photocourtesy of Allan Spradling..............................................................................................................................................................................1Trinity College Dublin, Dublin, Ireland; 2Department of Microbiology and Immunology, Department of Pediatrics, Dalhousie University, Halifax, Canada; 3CarnegieInstitution for Science and Howard Hughes Medical Institute, Baltimore, MD, USA; 4School of Applied Sciences, Edinburgh Napier University, Scotland, UK.Correspondence to Neville Cobbe: cobben@tcd.ie.© 2023 Cobbe et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after thepublication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).Rockefeller University Press https://doi.org/10.1083/jcb.202311145 1 of 3J. Cell Biol. 2024 Vol. 223 No. 1 e202311145Downloaded from http://rupress.org/jcb/article-pdf/223/1/e202311145/1921661/jcb_202311145.pdf by guest on 12 December 2023Anatomy at the Johns Hopkins University School of Medicine(1992–1995), using her immunofluorescence microscopy skills incollaboratively exploring the mitotic function of an essentialkinesin-like protein (Heck et al., 1993). During Margarete andBill’s time in Baltimore, they had two children, Charles (born1991) and Irina (born 1993). Both went on to study medicine andwere on the front lines during the COVID pandemic. They arealso both on track to become fifth-generation Heck PhDs(Charles in melanoma immunology at the University of Man-chester and Irina in radiation oncology at the University ofEdinburgh).Margarete and Bill were recruited to the University of Ed-inburgh as part of a drive initiated by Adrian Bird and the lateSir Kenneth Murray (1930–2013) to establish a center for cellbiology there. The family moved to Scotland in 1996. They livedin a cottage amid scenic woodland and fields near Peebles, ex-tending warm hospitality to family, friends, and visiting col-leagues over many years. Margarete was initially awarded aSenior Research Fellowship by theWellcome Trust (1996–2005),managing an active research lab in the College of Science andEngineering while also serving for many years as both programdirector for the Masters by Research in the Biomedical Sciencesand deputy director of the pioneering Wellcome Trust 4-yearPhD program in “The Cellular and Molecular Basis of Disease”(running one of the three modules of the program at the Well-come Centre for Cell Biology). She continued to demonstrateboth collaborative collegiality and independent novelty in thepublication of highly cited papers analyzing conserved proteinsfor which Drosophila mutants displayed pronounced defects inchromosome condensation and segregation (Loupart et al.,2000; Warren et al., 2000; Steffensen et al., 2001; Cobbe andHeck, 2004), as well as characterizing a novel metalloprotease(invadolysin) that was found to link mitosis with cell migration(McHugh et al., 2004).Margarete was then recruited to the University of Edin-burgh’s College of Medicine and Veterinary Medicine by SirJohn Savill and John Mullins, supported by a Wellcome TrustUniversity Award (2006–2011). She was attracted by the inter-disciplinary nature of the Centre for Cardiovascular Science, andher work with Drosophila opened new opportunities for usingmodel organisms in cardiovascular research. Here she continuedto focus primarily on the mechanism of action of invadolysin,using both Drosophila and vertebrate models, provocatively re-vealing localization of the protein to the surface of intracellularlipid droplets (Cobbe et al., 2009) as well as demonstrating itsessential roles in Drosophila mitochondrial function (Di Caraet al., 2013) and zebrafish cell migration (Vass and Heck,2013). Her group also demonstrated a novel, unexpected rolefor an Elongator complex subunit in insulin signaling (Bolukbasiet al., 2012). Her research led to an active involvement with theinternational community of protease researchers, with in-vitations to talk at conferences around the world. She served onthe council of the International Proteolysis Society and editedtheir newsletter “QuickCuts.” Characteristically for Margarete,when she attended the International Congress of Cell Biology inHyderabad in 2018, she agreed to give a careers lecture at a localteachers college, and was an immediate star, being featured inthe local newspapers and television.Margarete gained a Personal Chair in Cell Biology and Ge-netics at the age of 48 and became the first female professor inthe Centre for Cardiovascular Science. The title of her inaugurallecture was “Time flies like an arrow, fruit flies like a banana,”an homage to the Marx Brothers, reflecting her flair in mixinghumor with a serious scientific focus.Margarete was at once precise and analytical, and touchinglysentimental. Not only was she deeply devoted to her family (andjustifiably proud of their achievements), but she cared enor-mously for all who worked with her, wholeheartedly encour-aging them to do their best with integrity—regardless of thefield in which theymight ultimately find themselves. Margarete,indeed, was not only a scientific mentor but a life coach and areal friend for all her trainees, always ready to encourage andadvise them in pursuing their goals. One of Margarete’s recur-rent and inspirational quotes was, “Nobody is going to take careof your career if not yourself.” This advice has inspired many topersist and push and achieve their goals in their careers andbeyond. Consistent with her enduring concern for the welfare ofMargarete Heck with her postdoctoral advisor, Allan Spradling, at the ColdSpring Harbor Laboratory, 1989. Photo courtesy of Allan Spradling.The Heck lab in 2009, depicting (from left to right) Sharron Vass, MargareteHeck, Neville Cobbe, Edward Duca, Ekin Bolukbasi, Ching-Wen Chang, andFrancesca Di Cara. Photo courtesy of Sharron Vass.Cobbe et al. Journal of Cell Biology 2 of 3Margarete Heck (1959–2023): Cell biologist, geneticist, and incandescent social spark https://doi.org/10.1083/jcb.202311145Downloaded from http://rupress.org/jcb/article-pdf/223/1/e202311145/1921661/jcb_202311145.pdf by guest on 12 December 2023others’ careers, she participated in a Gordon Research Seminarcareer panel in 2014 and a GRC Power Hour in 2019 to addresschallenges faced by women in science (alongside issues of diver-sity and inclusion). Her collegiality within the wider UK cell bio-logy community was abundantly evident in her sustained serviceas a BSCB Ambassador for the British Society for Cell Biology, aswell as her co-organizing many highly successful conferences.Indeed, Margarete’s commitment to research student inter-ests was evident throughout her long-standing capacity aspostgraduate director for the Deanery of Clinical Sciences, pro-viding enthusiastic and practical direct support for individualstudents, while also contributing constructively as a member ofboth the College Postgraduate Board of Examiners and the Col-lege Researcher Experience Committee. Even during her finalstage with cancer, Margarete prioritized the ongoing support ofher last PhD student through both thesis submission and theviva process (equivalent to a thesis defense), which was suc-cessfully completed only a week before her death. Strikingly,Margarete remained positive to the end, bravely and selflesslyfocused on trying to make things better for others while per-sonally thankful for what she had.On the day of her funeral (September 7, 2023), the flag of OldCollege, University of Edinburgh, was flown at half-mast as amark of respect to Margarete, a gesture she would have beendeeply humbled by. The funeral was a quiet family affair, andwas officiated by the same humanist celebrant who had marriedIrina to Steve Lovejoy in a field above the house in May 2022. Atthat wedding, Margarete had asked the celebrant if she wouldofficiate at her own funeral. A month after the funeral, a largenumber of friends, family, former doctoral students, and col-leagues gathered at the Eastgate Theatre, Peebles, on October 22,2023, for a ceremony of love and celebration planned by Mar-garete and inspired in part by George Ezra’s song lyric, “You’dbetter throw a party on the day that I die” (“Green Green Grass”).In characteristic Margarete style, the party featured an aptlynamed cocktail, “The Last Word,” chosen especially by her.It is little wonder that the many personal tributes followingher death have described Margarete as a truly remarkablewoman who had a profound impact on the careers and lives ofthose she encountered and encouraged, remembering not onlyher intellectual contributions but also her convivial zest for life,her kindness and generosity, her joyful sense of humor, andespecially her radiant smile. She is fondly remembered anddeeply missed.AcknowledgmentThe authors thank Edie Stern for helping to edit the manuscript.ReferencesBolukbasi, E., et al. 2012. Open Biol. https://doi.org/10.1098/rsob.110031Cobbe, N., and M.M.S. Heck. 2004. Mol. Biol. Evol. https://doi.org/10.1093/molbev/msh023Cobbe, N., et al. 2009. J. Cell Sci. https://doi.org/10.1242/jcs.044610Di Cara, F., et al.. 2013. J. Cell Sci. https://doi.org/10.1242/jcs.133306Earnshaw, W.C., et al. 1985. J. Cell Biol. https://doi.org/10.1083/jcb.100.5.1706Earnshaw, W.C., and M.M. Heck. 1985. J. Cell Biol.https://doi.org/10.1083/jcb.100.5.1716Heck, M.M., et al. 1993. J. Cell Biol. https://doi.org/10.1083/jcb.123.3.665Heck, M.M., and A.C. Spradling. 1990. J. Cell Biol. https://doi.org/10.1083/jcb.110.4.903Heck, M.M., andW.C. Earnshaw. 1986. J. Cell Biol. https://doi.org/10.1083/jcb.103.6.2569Heck, M.M., et al. 1988. Proc. Natl. Acad. Sci. USA. https://doi.org/10.1073/pnas.85.4.1086Loupart, M.-L., et al. 2000. Curr. Biol. https://doi.org/10.1016/S0960-9822(00)00844-7McHugh, B., et al. 2004. J. Cell Biol. https://doi.org/10.1083/jcb.200405155Steffensen, S., et al. 2001. Curr. Biol. https://doi.org/10.1016/S0960-9822(01)00096-3Vass, S., and M.M.S. Heck. 2013. Exp. Cell Res. https://doi.org/10.1016/j.yexcr.2013.02.005Warren,W.D., et al. 2000. Curr. Biol. https://doi.org/10.1016/S0960-9822(00)00806-XMargarete Heck and Bill Earnshaw together. As Margarete wrote to her manyfriends in August 2021 (only months after the recurrence of ovarian cancerwas diagnosed), “I thank my lucky stars every day for the many blessings ofmy life!” Photo courtesy of Bill Earnshaw.Cobbe et al. Journal of Cell Biology 3 of 3Margarete Heck (1959–2023): Cell biologist, geneticist, and incandescent social spark https://doi.org/10.1083/jcb.202311145Downloaded from http://rupress.org/jcb/article-pdf/223/1/e202311145/1921661/jcb_202311145.pdf by guest on 12 December 2023

Margarete Heck (1959–2023): Cell biologist, geneticist, and incandescent social spark

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Margarete Heck (1959–2023): Cell biologist, geneticist, and incandescent social spark

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