A fly geneticist’s journey into discovering rules of organ development

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

The first installment of the 2024 GSA Awards seminar series on May 16, at 1:00 p.m. EDT, will feature Deborah Andrew describing 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 will also share recent efforts using genome-wide approaches to discover how functional enhancers of downstream target genes are organized. Save the date and register 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.