Early-Stage Discovery: How Wistar’s Genomics Facility Drives Wistar Science

Meet Sonali Majumdar, M.S., managing director of The Wistar Institute Genomics Facility, a hub that turns biological material into the data scientists need. Ms. Majumdar discussed the ins and outs of genomics technology and how Wistar Science depends on it.

Wistar’s Genomics Core Facility houses the latest and greatest scientific instruments, some of the most advanced (and expensive-to-use) biomedical technology in the building — in this understated laboratory are machines that manipulate the very fabric of life. These machines are genomic sequencers: counters of DNA and RNA molecules that form the foundation of our biology. Genomics Facility managing director Sonali Majumdar, M.S., has presided over a top-notch team of sequencing experts for nearly ten years, and their work sustains the foundational research of scientists both in- and outside the Institute.

“Genes are the beginning,” says Sonali. “Generally, when people want to discover something, they’ll do a genomics study — so they come to us.”

Every cell in our bodies contains our genome, a vast amount of biological information comprising every set of base pairs on every chromosome. But humans aren’t homogenous biological masses of cells; our bodies have different types and arrangements of cells for different functions. In short: not every gene in our genome gets “expressed,” or turned on, because complex life demands complex variety. To understand how or why certain things happen in our cells, scientists need to understand which genes do what — that’s what Sonali and her team at Genomics Core Facility do.

“Our cells have more than twenty thousand genes that can theoretically get turned into proteins,” she explains. “As a scientist, you want to know which of those genes affect your project. Take cancer, for example. We can broadly sequence cancer tissue and compare that with similar tissue from an apparently healthy individual. The scientist can see, that out of twenty thousand genes, maybe one hundred or so may play a role in the cancer. Then we can look at sequencing data for each gene individually.”

At the most basic level, sequencing “counts” genomic elements. Though newer machines like Wistar’s nanopore sequencer can perform long-read sequencing (read unabridged descriptions of base-pair sequences of T, C, A, and G), most sequencing methods identify key snapshots of the genome and then use computational methods to reassemble the full sequence.

At the broadest levels of sequencing, the process is like looking for needles in haystacks; scientists look for patterns that occur on enormous scales. But the opportunity to find something genuinely new keeps her passionate.

Managing the Genomics Core is a huge undertaking, and not just because of the volume of tasks. In the world of biomedical research, where scientists’ scope is largely determined by how much money they have for their projects, genomic studies and sequencing can take up hefty portions of budgets. When her team executes their analyses, science isn’t the only thing at stake — so is grant money.

“The materials and solutions that genomics studies use are incredibly expensive, and the steps we take to sequence samples properly require absolute precision; if a process isn’t followed correctly, that mistake might cost hundreds or thousands of dollars,” says Sonali. “There’s one step for our single-cell sequencer where, if you don’t add the solution extremely carefully, that’s an instant $2,000 down the drain.”

Grant dollars may be precious, but scientists happily pay for genomics and sequencing because the technology is so vital to such a broad swath of biomedical research, and Wistar’s Genomics Core Facility delivers quality data thanks to a team of dedicated experts and state-of-the-science equipment. In 2023, Wistar completed the installation of new spatial molecular profiling technology which allows for spatial phenotyping of millions of cells at an unprecedented scale and speed. This equipment was purchased thanks to the generosity of The Horace W. Goldsmith Foundation through Wistar’s Bold Science//Global Impact Campaign and the estate of Robert A. Fox.

“We take our work very seriously because, yes, money and data are on the line. Delivering results to scientists takes precision, and that’s what we strive for,” says Sonali. With more than a dozen specialty genomics services available, Wistar’s Genomics Core Facility is state-of-the-science — a state that, according to Sonali Majumdar, should excite anyone invested in biomedical discovery.

“Genomics has come a long way,” she says. “Single-cell sequencing can show us expression levels in specific cells, so we can tell which genes are doing what in a variety of cell types or tissues. And with the rise of spatial sequencing, we can even create a map of gene expression across a tissue: this gene is highly expressed in this region, not very expressed in that region, and so on.”

As Wistar continues to pursue early-stage discoveries through its new Center for Advanced Therapeutics, genomics will only become more important. In seeking to revolutionize drug discovery by using the latest and greatest in biomedical research methods, the new Center for Advanced Therapeutics will depend on the advanced capabilities of the Genomics Core Facility to indicate whether possible drugs work and how they can be improved.

“This is just the beginning of new genomics techniques throughout biomedical research,” says Sonali. “As sequencing technologies become less expensive and more advanced, we’re only going to see more exciting developments. That’s why I love this field: genomics is where the action is.”