Elisabetta Ullu, a brilliant scientist who made seminal contributions to the fields of RNA biology and parasitology, died on September 8, 2014, at the Connecticut Hospice in Branford, CT, following a heroic 21 year battle with breast cancer. She was a woman who brought intelligence, style, and warmth to all aspects of her life, both personal and professional.
Elisabetta was Professor of Medicine (Infectious Diseases) and of Cell Biology at the Yale School of Medicine. An intellectual titan and talented experimentalist, Elisabetta was one of the most inspiring scientists, mentors and teachers of our time. Her influence and impact on the field of parasitology was immeasurable, not only because of her expertise but, more importantly, because of her humanity. Deeply caring and compassionate, Elisabetta was a dedicated mentor to students and scientists at all levels. She was a tireless and outspoken advocate who supported the career development of numerous junior scientists. Her legacy includes both her unselfish mentorship and support of junior scientists, as well as her own considerable scientific discoveries.
Elisabetta was born February 7, 1951, in Rome, Italy. Her mother, a high school classics teacher, provided her earliest intellectual foundations. She began her scientific career as a graduate student at the University of Rome in 1973 under Antonio Fantoni, where she studied the expression of embryonic globin genes in the mouse, becoming an expert on polysome gradients and in vitro translation systems. The dedicated training and mentoring she received during this period laid the groundwork that allowed her to become an outstanding scientist. From 1978 to 1982 she was a postdoctoral fellow under Marialuisa Melli at the European Molecular Biology Laboratory in Heidelberg, Germany, where she met Christian Tschudi, her future husband. Continuing the work she began in Heidelberg she joined Alan Weiner’s laboratory at Yale University in 1982 performing seminal experiments in which she determined the nucleotide sequence of the human 7SL RNA, characterized its relationship to the Alu family of repetitive sequences, and identified the genes responsible for transcribing this RNA. She generously made her as yet unpublished 7SL RNA sequence available to Peter Walter, a critical factor allowing Peter to identify this RNA as the RNA component of the signal recognition particle. This discovery occurred during a “historical” conversation with Peter in March 1982, less than one month after Elisabetta arrived at Yale University.
In 1985 Elisabetta decided to switch her focus to Trypanosoma brucei, the human parasite that causes sleeping sickness, a disease that is medically and economically devastating. She was recruited to the MacArthur Center for Molecular Parasitology by the late Dr. Frank F. Richards, with the idea of using her immense expertise in molecular biology to advance the understanding of gene expression in this parasite. This was the beginning of a long and extremely productive collaboration with her husband. Elisabetta developed the tools needed to dissect the function of small nuclear RNAs in trypanosome splicing, which allowed her to demonstrate mechanistic similarities between the trans-splicing pathway utilized by this parasite and the cis-splicing pathway used in human cells. Next, Elisabetta showed that transcription by RNA polymerase II generates polycistronic mRNAs that are processed by concerted action of trans-splicing and polyadenylation, a discovery that explained why trypanosome gene expression depends on trans-splicing. In further elegant experiments, she showed that trans-splicing and polyadenylation are linked and identified sequences in the mRNA that are essential for this coupling. Indeed, more recent genome-wide mapping of trans-splicing and polyadenylation sites performed by her group confirmed the spatial cross-talk between these machineries.
In 1998, Elisabetta’s research took a serendipitous turn when she discovered RNA interference (RNAi) in trypanosomes. RNAi is a phenomenon in which small, noncoding RNA molecules rather than proteins regulate gene expression. This discovery revolutionized the field of trypanosome biology, as it allowed investigators to use RNAi as a tool to explore the functions of hundreds of genes, both for individual research purposes and for genome-wide screens. Importantly, the validation of a large number of potential drug targets to combat trypanosome infection were made possible by Elisabetta’s initial discovery of RNAi and by the many tools that she created to manipulate gene expression using this pathway.
After this discovery, Elisabetta focused on determining the biological function of RNAi and identifying the cellular machinery required for this pathway. She personally generated the first siRNA library for trypanosomes and demonstrated that siRNAs are involved in silencing of retroposons and that siRNAs associate with translating ribosomes. Together with Steve Beverley (Washington University), she discovered that although many Leishmania species had lost the ability to carry out RNAi, the machinery was retained in Leishmania braziliensis. More recently, Elisabetta discovered two additional core RNAi factors. The detailed understanding of the T. brucei RNAi mechanism pioneered by Elisabetta will be beneficial not only toward improving RNAi as a tool for discovery, but also for reconstructing the pathway in RNAi-deficient pathogens like Leishmania major or even Plasmodium falciparum.
In the past five years, Elisabetta’s research addressed the central question of how trypanosomes become infectious. T. brucei undergoes a complex life cycle between the mammalian host and the blood-feeding tsetse fly vector. This lifecycle necessitates changes in cell morphology, metabolism, signaling pathways and gene expression, and these parasites have evolved adaptations that allow them to survive in both the gut and salivary glands of the tsetse fly, as well as in the bloodstream of their mammalian host. By overexpressing a single RNA-binding protein (RBP6) in non-infectious trypanosomes, Elisabetta, together with Christian Tschudi, recapitulated in vitro the events leading to acquisition of infectivity. This discovery opens the way to dissect T. brucei development in vitro and to understand the molecular basis for infectivity acquisition.
Elisabetta’s accomplishments have been recognized with numerous honors. She received a New Faculty Award from the Yale MacArthur Center for Molecular Parasitology, a Burroughs Wellcome Scholar Award in Molecular Parasitology and was named a Senior Scholar in Global Infectious Diseases by the Ellison Medical Foundation. In recognition of her groundbreaking research on the RNAi machinery, she received a 10 year MERIT award from the National Institutes of Health. In 2011, she was elected as a Fellow of the American Academy of Microbiology. Most recently, Elisabetta was the inaugural recipient of the American Society for Biochemistry’s Alice and C.C. Wang Award. This new award recognizes established investigators who make seminal contributions to the field of molecular parasitology, focusing in particular on novel and significant discoveries on the biology of parasitic organisms.
Among her many professional accomplishments, Elisabetta was a member of the Genome and Tropical Medicine and Parasitology Study Sections of the National Institutes of Health, and was Co-Director of the NIH training grant in Molecular Parasitology at Yale. She continuously contributed to the scientific community by serving on the editorial boards of several prestigious journals in microbiology (Annual Review of Microbiology, Eukaryotic Cell, Molecular Microbiology, and PLoS Pathogens). She served on the Advisory Committee for the Wellcome Trust, the European Malaria Network and on the review board for the Ellison Biomedical Foundation. At the Marine Biological Laboratory in Woods Hole, MA, Elisabetta was a co-organizer of the Molecular Parasitology meeting from 1995 to 1997, and served as the Co-Director of the Biology of Parasitism Course in 2002. She also served as chair for the Gordon Research Conference on Host-Parasite Interactions.
In addition to her love and dedication to science, Elisabetta was a committed teacher and mentor, especially to women scientists. Elisabetta had very high standards for what constitutes excellent science, which was clearly evident in her publications. She was interested in work far beyond her own areas of RNA biology and parasitology, and could drill down to the important question, the key data, in any scientific argument. Many junior colleagues benefited immensely from her intellectual insights. Elisabetta would not only find the weak spot in their arguments, but also turn her full attention and focus as to how that weakness could be addressed. She read their manuscripts and proposals, gave advice on navigating life as an academic scientist, and advocated ceaselessly on behalf of her junior colleagues in her section and department and beyond Yale. Because of the caliber of her science, her dedication, her impressive achievements, her brilliant mind and her incredible humanity, she functioned as a role model for many scientists, both male and female, both at Yale and within the parasitology field.
Elisabetta also took great pleasure in life and made others see the beauty and possibility of their surroundings. To newcomers, New Haven initially often appeared rather small and grim. Seen through Elisabetta’s eyes, it was transformed into an almost-magical place of beautiful coastlines, places to buy fresh clams or the best mozzarella, neighborhood restaurants with a special dish or wine on the menu, artists and yogis and interesting people who were not scientists. She threw the best parties, from intimate dinners to large laboratory gatherings, cooking with the same confidence, style, and precision that she brought to her scientific endeavors. All gravitated to Elisabetta’s home, where fantastic food and conversation were always in abundance, and dogs and children constantly ran circles around everyone, but never got in the way.
She is survived by her husband and research partner, Christian Tschudi, family in Switzerland and Italy, as well as friends across the world who considered her to be an important member of their families.
A memorial service will be held at Battell Chapel in New Haven, CT on Sunday, November 9th, 2014 at 3 pm. In remembrance of Elisabetta’s vibrant and joyful life, please dress comfortably in bright colors.
In lieu of flowers, please consider a contribution in memory of Elisabetta Ullu to the Closer to Free Fund, which jointly supports Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven. Please make checks payable to Closer to Free Fund and earmarked for Breast Cancer research, and mail to P. O. Box 7611, New Haven, CT 06519-0611. Secure on-line gifts can be made at www.giveclosertofree.org.