Deborah Andrew’s journey from a first-generation college student to a leader in fruit fly genetics is nothing short of inspiring. She began her undergraduate studies in freshwater ecology; during that time, she took a genetics class taught by fruit fly geneticist David Kuhn that changed the course of her career. She worked in fruit fly genetics laboratories throughout her academic training to understand the role of homeotic genes in organ formation. Andrew, now the Bayard Halsted Professor of Cell Biology at the Johns Hopkins University School of Medicine, is still dedicated to studying organogenesis, particularly in uncovering genetic mechanisms governing tubular structures in Drosophila.

Mapping tubular structures from birth to morphogenesis

“I have always been interested in the questions about how a relatively nondescript fertilized egg turns into the multitude of specialized cell types found in the mature organism. Interested in organ formation, I began addressing the following questions: How is organ fate specified? How do organs specialize? How do they achieve their normal morphologies?” explains Andrew. Harnessing the power of genetic tractability in Drosophila, her pioneering work addressed fundamental mysteries in the salivary gland (digestive system) and trachea (respiratory system) development.

Andrew’s group made considerable strides toward understanding how an organ develops in its primordial state and achieves a final functional morphology by identifying the major transcription factors that control these processes at different stages of embryonic development. The major regulators of organ specification and function are known for only a small handful of organs in even fewer organisms. Remarkably, Andrew’s work identified major regulatory genes for salivary gland and trachea development and their interactions with downstream target genes. 

The salivary gland contains specialized cells with very high levels of secretion. The discovery of a conserved bZip-family transcription factor CrebA as the major regulator of increased secretory capacity is one of the most important findings from Andrew’s research group. “CrebA upregulates nearly all secretory pathway component genes, including genes encoding the protein components of the ER, Golgi, and secretory vesicles, as well as the genes that encode the proteins that transport nascent polypeptides to secretory organelles. This single transcription factor—CrebA—upregulates all of those,” emphasizes Andrew.

From fundamental biology to a direct impact on human health

Discovering conserved positive regulators of tube formation and secretion processes, Andrew’s work showed tremendous potential in developing artificial salivary glands and conferring secretory abilities to non-secretory cells. Her lab showed that each of the five human orthologues of CrebA could also induce the expression of secretory pathway component genes in fly embryos, highlighting the functional conservation of this gene family. Indeed, by expressing the closest mammalian ortholog of CrebA in HeLa cells, her group showed a similar upregulation in human secretory pathway gene expression. Such strategies could help ramp up the production of secretory products in biotherapeutic applications.

Andrew used her expertise in the Drosophila salivary gland to study the orthologous structure in Anopheles mosquitoes. The malaria-causing parasite Plasmodium migrates to the salivary gland ready to be injected into the vertebrate host at the time of feeding. Her group identified another transcription factor Sage that expresses only in the salivary gland. When knocked out from the Drosophila salivary gland cells, cells die massively via apoptosis. Now, her lab is using CRISPR technology to knockdown Sage from mosquito salivary glands in the hope of achieving cell death. “Moreover, Andrew has shown that the polarized architecture of the salivary gland acts as a natural barrier for parasite transmission. This line of investigation is likely to generate new targets for transmission-blocking strategies,” says Geraldine Seydoux, Professor of Molecular Biology and Genetics at Johns Hopkins University and long-time colleague and collaborator of Andrew.

A beloved mentor and community leader

Throughout her career at the Johns Hopkins School of Medicine, Andrew considered herself privileged to work with young scientists, and her trainees returned the feeling. Andrew’s former trainee Caitlin Hanlon described her as an incredible mentor who always showed confidence in what her trainees could achieve. “Her dedication to helping train people and showing up for them created a wonderful and meaningful work culture not just in the laboratory but also in the department,” says Hanlon, who is now an Associate Professor at Quinnipiac University. Andrew also contributed to teaching efforts at Johns Hopkins. She dedicated countless hours teaching medical and graduate students the fundamentals of cell biology and physiology, keenly elucidating how things really work at the basic level in any cell. 

In addition to being a leader in her research field, Andrew generously offered her time and expertise to build fly genetics and development biology communities. She served as a representative to the Drosophila Board (“Fly Board”) from 1996 to 1999, as treasurer from 2013 to 2016, and president in 2017. She has organized major conferences over the years, including the Annual Drosophila Research Conference, the Santa Cruz Developmental Biology Meeting, and a Gordon Research Conference. She has been a long-term member of the Drosophila Genetics Resource Center Advisory Board.

Beyond her exemplary research and community work, Andrew is a fierce advocate of fundamental research and the fruit fly model system. “I would like more people to enter the Drosophila field. While we can do so many things in other systems, such as humans and mice, I strongly believe you get more bang for your buck in fly research,” emphasizes Andrew for scientists in training, encouraging them with a firm belief that what can be discovered in flies cannot easily be discovered anywhere else.

Join us in congratulating Deborah Andrew, who received the George W. Beadle Award at The Allied Genetics Conference 2024 in Metro Washington, DC.

2024 GSA Awards Seminar Series

In the first installment of the 2024 GSA Awards seminar series, Deborah Andrew described her lab’s findings on how the Drosophila salivary gland is first specified and maintained, and how early and continuously expressed transcription factors control both secretory capacity and specificity. She also shared recent efforts using genome-wide approaches to discover how functional enhancers of downstream target genes are organized. Watch the recording here!

Sejal Davla, PhD, is a neuroscientist, science writer, and data scientist with expertise in research in a variety of life sciences. She has more than a decade of experience studying the brain by using cutting-edge methodologies in microscopy, molecular biology, genetics, and biochemistry, and is a motivated storyteller and science communicator.

Ellsworth (Ed) Grell blessed the Drosophila community through three enduring legacies: as a pioneer of chromosome mechanics, as a primary organizer and synthesizer of genetic knowledge in Drosophila, and as a graceful mentor to those fortunate to have known him personally.

Ed grew up in rural Nebraska, completed his undergraduate studies at Iowa State, and trained with E.B. Lewis as a graduate student at Caltech, insightfully analyzing the role of two interacting genes involved in the degradation of the amino acid lysine in his doctoral thesis.¹ It was also in the Lewis lab that Ed met and then married his lifetime genetics colleague and soulmate Rhoda Frank Grell. They moved to Oak Ridge, Tennessee, where Ed remained until 1985.

Throughout his career, Ed contributed to developing precisely engineered chromosomes central to creating chromosome balancers, targeted translocations, or chromosome fusions.^2-6 He used these sophisticated genomic tools to follow complex genetic traits in insightful and imaginative ways. For example, Ed was a leader in the arena of linking molecular phenotypes to genetic polymorphisms and enzyme dosage effects, using what were then cutting-edge gel electrophoresis techniques.^7,8 Ed also collaborated with Dan Lindsley at the Oak Ridge National Labs to investigate the genetic basis of spermatogenesis, finding that the haploid post-meiotic phase to generate functional spermatids could proceed in the absence of chromosomes.⁹

Ed is perhaps most appreciated by the Drosophila community for his collaborative work with Dan Lindsley in assembling the “Genetic Variations of Drosophila melanogaster,” commonly referred to affectionately as the Red Book (because of its cover’s color). This wonderful reference book by Lindsley and Grell, published in 1968, distilled all phenotypic and genetic information regarding known Drosophila mutants at the time and provided helpful hints such as ranking mutant alleles on an RK scale based on scoring difficulty. Theodosius Dobzhansky succinctly summarized the achievement of this opus in his Science book review:¹⁰

“Here, at last, is the long-awaited compendium and a guide to the study of the genic and chromosomal variations in Drosophila melanogaster described in world literature. The book modestly calls itself a revision of the C.B. Bridges and K.S. Brehme’s The Mutants of Drosophila melanogaster, published almost a quarter of a century ago. In fact, it is a new and monumental work, embodying what must have been a prodigious amount of meticulous and conscientious work on the part of the authors.”

When Oak Ridge closed down its Genetics Section in 1985, Ed relocated to the Bay Area where he became a central member of the research group led by Lily and Yuh Nung Jan at UC San Francisco until his retirement. Ed helped design both small- and large-scale genetic efforts in the Jan lab and patiently mentored those of us new to the field, sharing his many clever tricks of the trade and his deep historical knowledge of the field. He was a gentle and humble gem of a human being and I feel fortunate to have known him as both a close colleague and friend.

Acknowledgements: Thank you to Lily and Yuh Nung Jan, Susan Younger, Kimberly McCall, and other members of the Jan lab who kindly shared their thoughts and memories of Ed. Thanks also to James Birchler for sharing memories of Ed from his Oak Ridge days and to Michael Mislove for his insights and experience growing up with Ed and Rhoda in their warm and intellectually engaging household.

References:

1. Grell EH. Genetics and Biochemistry of “Red Cells” in Drosophila melanogaster. Dissertation (Ph.D.), California Institute of Technology. 1958. Doi: 10.7907/B5AB-S991.
2. Grell RF, Grell EH. The Behavior of Nonhomologous Chromosomal Elements Involved in Nonrandom Assortment in Drosophila Melanogaster. Proc Natl Acad Sci U S A. 1960;46:51-57.
3. Brosseau GE, Nicoletti B, Grell EH, et al. Production of Altered Y Chromosomes Bearing Specific Sections of the X Chromosome in Drosophila. Genetics. 1961;46:339-346.
4. Grell EH. Variations in Preferential Segregation of Chromosome Two in Triploid Females of Drosophila Melanogaster. Genetics. 1961;46:1267-1271.
5. Grell EH. Distributive Pairing of Compound Chromosomes in Females of Drosophila Melanogaster. Genetics. 1963;48:1217-1229.
6. Twardzik DR, Grell EH, Jacobson KB. Mechanism of suppression in Drosophila: a chance in tyrosine transfer RNA. J Mol Biol. 1971;57:231-245.
7. Grell EH, Jacobson KB, Murphy JB. Alcohol Dehydrogenase in Drosophila melanogaster: Isozymes and Genetic Variants. Science. 1965;149:80-82.
8. Grell EH. Genetic Analysis of Aspartate Aminotransferase Isozymes from Hybrids between DROSOPHILA MELANOGASTER and DROSOPHILA SIMULANS and Mutagen-Induced Isozyme Variants. Genetics. 1976;83:753-764.
9. Lindsley DL, Grell EH. Spermiogenesis without chromosomes in Drosophila melanogaster. Genetics. 1969;61:Suppl:69-78.
10. Lindsley DL, Grell EH. Drosophila Handbook: Genetic Variations of Drosophila melanogaster. Science. 1968;162:993.

In 2020, the Fly Board voted to use part of its reserve fund to support efforts to increase trainee participation as well as equity and diversity in the Drosophila community. An awards committee decides how the money will be spent each year, and from 2020–2022, the committee posted a very broad call for applications from non-profit programs that introduce middle school, high school, or college students to Drosophila research. Five or six such applications were funded in each of the three years, and the programs have recruited a diverse set of students worldwide to learn about working with flies. This year’s awarded programs and individuals are:

eCLOSE provides training in genetics research to participants from age 10 through retirement. The Fly Board award supported eight undergraduates in their most advanced program, the Undergraduate Bridge to Research. Over the course of 10 weeks during the summer, participants identified a major health challenge facing a community that was meaningful to them on a personal level. They conducted a chemical genetic screen to identify nutrients that might alter phenotypes in fly models of the disease of interest. Leveraging those results, the students designed independent research projects ranging from biochemical analysis of signaling pathways to developmental biology of ovaries, brains, intestines, and social behavior changes among treated and/or mutant flies. Two students have already attained research positions in fly labs, with plans to use their work for honors thesis and capstone projects as they complete their undergraduate degrees. The Fly Board award provided the reagents and materials needed for students to conduct their independent work, expanding the experimental options available and increasing the depth of the research. 

The Drosophila Stock Center at the University of Mysore, Karnataka, India is currently maintaining a collection of 50 Drosophila species and over 2,000 stocks that are provided to researchers and teaching faculty at colleges and universities in India for use in teaching and learning genetics. The Stock Center also trains teachers and individual researchers through hands-on training workshops and short-term collaborations. The Fly Board funding was used to support a hands-on training program in December 2023 to introduce teachers of undergraduate students in India to lab techniques that they can then use in their classes. The workshop covered morphology, genetic mutants, polytene chromosome inversions, use of Drosophila for understanding biological inheritance, behavioral exercises, collection and categorization of wild type Drosophila, study of polygenic traits, and study of gene expression using reporter constructs.

Games of Flies and Genes is the new, ambitious project of Engage Nepal with Science that will be supported by Fly Board funding. It aims to encourage science educators in Nepal to work collaboratively with fly researchers to make their genetics lessons more interactive and dynamic and facilitate the learning of this important part of the biology curriculum. The project involves four fly researchers from the US and Nepal, who will work directly with educators and students from five schools in Nepal to explore Drosophila genetics and gain hands-on experience with fly research by visiting the Research Institute for Bioscience and Biotechnology. Participants will learn about Drosophila through various engaging methods, look at flies under the microscope, play a game based on genes and laws of heredity, and will also make their own fly models with modeling clay. These workshops have the potential to revolutionize the field of genetics education in Nepal, offering students an experience that will not only deepen their understanding of genetics but also inspire the next generation of scientists.

Osamu Shimmi is using Fly Board funding for an outreach initiative to improve Drosophila research and education in Estonia. His outreach efforts aim to develop easy-to-use study materials on Drosophila for middle and high school students in the Estonian language. He also writes articles for a popular science magazine to introduce Drosophila as a learning model for biology teachers in middle and high school. On September 29, 2023 he hosted school children in the lab as part of the activities for Science Day at the University of Tartu, Estonia, to promote Drosophila research through outreach.

Small But Mighty: Drosophila as a Powerful Tool for Biomedical Research is aimed at educating secondary school students in Akure, Nigeria, about the possibilities of Drosophila research, and providing them with educational materials to take back to their schools. The Fly Board-funded workshop was hosted at the Federal University of Technology Akure in November 2023 and featured lectures on basic Drosophila husbandry and genetics, practical hands-on activities, career talks, and more. Nilda Barbosa, a professor from the Universidade Federal de Santa Maria, Brazil, gave a virtual lecture, while Ganiyu Oboh and Adedayo Ademiluyi from the Federal University of Technology Akure, Nigeria spoke in person. This event had a large impact on awareness of Drosophila research in Nigeria and has the potential to be self-sustaining.

Enhancing Biology Education held a three-day workshop in November 2023, funded by the Fly Board, to train teachers-in-training (B.Sc(ed.)/B.Ed students) in Nigeria on the utilization of Drosophila as a cost-effective teaching tool in high school biology. Of the 20 in-person participants, 60% were females from underrepresented regions in Nigeria. Additional applicants were able to join virtually. The workshop ran from 9 a.m. to 6 p.m. each day and the curriculum included talks, practical sessions, and micro-teaching.