BSc, Human Biology, King’s College
PhD, Molecular Biology, University of London and European Molecular Biology Laboratory
Early training in theater and arts prepared Julia Zeitlinger, PhD, well for the many roles required of a researcher: experimenter, presenter, writer, artist, director, teacher, and mentor. Today she finds being at the forefront of research uncovering the rules that govern gene regulation just as thrilling and creative as staging a theater production.
Growing up in Germany, Zeitlinger loved math, science and the arts. The time she spent in school theater productions inspired dreams of becoming an actress. But ultimately, she fell in love with developmental biology during her anatomy classes in Germany and her first stint at laboratory research at King’s College London. Zeitlinger went on to earn a PhD in developmental genetics from the European Molecular Biology Laboratory in Heidelberg and pursued a postdoctoral fellowship at the Massachusetts Institute of Technology, intrigued by the up-and-coming field of genomics and an opportunity to reconnect with her love for math.
In 2007, she joined the Stowers Institute, where she found a perfect alignment with the Institute’s scientific research focus on genomics, transcription, and developmental biology. Since then she has combined her analytical skills and creativity to develop the latest genomics technologies and to understand the complexities of gene regulation during development. “We’re not pressured to develop a drug or cure disease and so this allows us to focus on fundamental problems,” Zeitlinger says. “We share this love of basic science.”
The Zeitlinger Lab focuses on how DNA sequence information in the genome controls gene regulation in Drosophila and mouse. Zeitlinger and her team hope to gain insight that can be applied to the human genome in development and disease.
Gene regulation is the process by which a cell determines which genes to turn on and off and when to create specific cells in the body, such as neurons, brain cells, or the cells that make up skin and bone. This process usually happens during transcription, when the information in a gene’s DNA is transcribed or transferred to RNA and involves transcription factors. Transcription factors bind to specific spots in the DNA to switch on and off certain genes. For many years, researchers studied genes and their genetic switches one by one. Now, Zeitlinger analyzes whole genomes to predict the fate of cells.
Among her many contributions to the field is the discovery of paused RNA polymerase II genome-wide. Previously, it was thought that once RNA polymerase, a critical enzyme in transcription, is recruited to the worksite, the process of transcription proceeds without a hitch. Zeitlinger found that RNA polymerase starts the transcription process, but then pauses, as if waiting for a signal to proceed. If paused polymerase is present, the gene is more likely to be activated in the future. The team’s genomic analysis of promoters, enhancers, and chromatin during development has shed light on their essential role in gene regulation.
The Zeitlinger Lab has also developed breakthrough genomic techniques that allow researchers to collect information from vast amounts of cells — sometimes numbering in the millions — to provide an accurate picture of how genes are regulated. Zeitlinger and her team developed ChIP-nexus, an innovative technique described in Nature Biotechnology in 2015, which gives investigators an accurate high-resolution map of transcription binding sites.
Now, Zeitlinger is applying a deep learning tool the team developed to a variety of ChIP-nexus data from different cell types and stages to better understand the cis-regulatory code and how it changes during development. At the same time, the team is developing a novel genomics technology, ChIP-next, that allows them to decipher cis-regulatory information from many fewer cells. A cis-regulatory module is a stretch of DNA where a number of transcription factors can bind and regulate expression of nearby genes and regulate their transcription rates. However, scientists have encountered challenges with collecting and mapping cis-sequence information due to insensitive and sparse data.
After years of hard work, the researchers are proving that the DNA sequences driving transcription and gene regulation are not the impenetrable black boxes once assumed. “This is something we’ve been working on for a long, long time. And for a long time, this problem just seemed too hard. Now we’re finally finding that it is solvable,” says Zeitlinger. “It’s been a huge learning curve and very exciting. That’s why I love my job – I love to learn.”