The science of images

Imaging scientists drive standards, provide tools to advance research

By Susan E.W. Spencer

At its core, science is about the possibility of translating data into discoveries. But throughout this process, it’s crucial to keep track of what the data mean.

UMass Chan Medical School researchers Caterina Strambio-De-Castillia, PhD, and David Grunwald, PhD, are among a growing cadre of imaging scientists who are developing pathways to turn data into discoveries. They are synchronizing the power of quantitative digital microscopy and research data management to advance science as a whole.

This work takes them from individual laboratories striving to make sense of groundbreaking—but huge—datasets to international communities of bioimaging scientists, microscope manufacturers and facility managers, in a quest to develop uniform standards. The goal? Imaging data that can be shared and important scientific findings that can be reproduced and validated.

David Grunwald, PhD, (above) and Caterina Strambio-De-Castillia, PhD, (below) describe themselves as occupying an in-between space, acting as a bridge between disciplines. Dr. Grunwald’s focus on microscopy hardware dovetails with the software analysis championed by Dr. Strambio-De-Castillia.

Photo by FAITH NINIVAGGI

“Right now, unfortunately, because of the complexity of image data,” Dr. Strambio-De-Castillia, assistant professor of molecular medicine and a cell biologist by training, said, “scientists are publishing quantitative results— the numbers—but it is hard to connect those results with the often-stunning images that are behind them.”

The foundation for the use of magnification as an observation and measurement tool for modern science goes back centuries. Scientists first had to be talented visual artists to capture what they saw by drawing in notebooks. Over time, cameras captured images of what could be seen through a typical light microscope and later, in advanced imaging technologies like electron microscopy. More recently, the digital revolution turned analog images—those captured on film—into electronic data.

But when it comes to sharing data captured in images, things have not improved much, explained Strambio-De-Castillia. But, with funding from the Chan Zuckerberg Initiative (CZI), she is working to change that.

The CZI, among its many goals, supports technological development for research tools in the life sciences because “better tools make every scientist a better scientist,” said former CZI head of science Cori Bargmann, PhD, in her commencement address to UMass Chan graduates earlier this year. Strambio-De-Castillia is passionately interested in finding those better tools.

Digging deeper in visual data

Over the years, optical tools such as electron microscopy and x-ray crystallography have become much more complex and the images they produce contain volumes more information, all of it gathered and stored digitally.

As scientists drilled further down into the molecular details of cellular functions over the past half century, it became important to know how the information gleaned could be integrated into a broader understanding of biological systems.

“Researchers are no longer just looking at all the DNA in the nucleus, all of the RNA, all of the proteins,” Strambio-De-Castillia said. “Scientists are understanding how all of these individual components work together, how they are dynamically organized in three dimensions and move over time.”

Similarly, Dr. Grunwald sees the underlying data to be critical to understanding—and reproducing—the science. Grunwald, associate professor of RNA therapeutics, considers his role akin to “a science concierge.” A biophysicist with a lengthy résumé of other skills, he is an expert in microscopes and how scientific images can tell a story. So, he does a typical hotel concierge one better. “I don’t secure a table,” he said, for a diner seeking a difficult reservation, “I create the table. It is an uncharted area, so it requires an exploration guide.”

Both Grunwald and Strambio-De-Castillia describe themselves as occupying an inbetween space, acting as a bridge between disciplines. And both agree their mission is to make science better.

“I established myself in the RNA and nuclear pore community but at my heart I am a tool maker and a physicist who deeply cares about knowing how well we measure what we measure,” Grunwald said.

As imaging technology has progressed, some have said that microscopes are too complicated now for precisely comparing images produced using one instrument with those produced on another, according to Grunwald. But he said, “At the end of the day, the microscope is a photon detector. We just need to count photons. We can compare that.”

Grunwald said the importance of calibrating microscopes and recording data about settings and equipment is even more urgent as technology advances. Materials and media change over the years in scientific instruments just as in digital home entertainment systems, photography and personal computers. Resolution gets pushed to higher levels. Critically, detailed documentation is needed so information isn’t lost when the next technological advance comes into use.

Grunwald’s focus on microscopy hardware dovetails with the software analyses championed by Strambio-De-Castillia.

Strambio-De-Castillia is not only a cell biologist, but she also studied computer science and incorporates that expertise into her work. She explained her role involves helping other scientists with data stewardship. “It’s not just the question of cataloging the data; it’s actually learning what is the important information you need to have and developing software tools that capture the key information so that it can be found later,” she said.

This analysis is becoming essential as grant funders such as the National Institutes of Health are enforcing requirements that applicants commit to research data management plans, in which sharable data must be made available.

Above all, image scientists want to help researchers get the most information out of their work, not only to advance knowledge but also to maximize efficiency of substantial resource investment.

From UMass Chan to the global stage

In the research labs at UMass Chan, Grunwald and Strambio-De-Castillia help scientists across different specialties collaborate to translate their data into cancer drugs and gene therapies.

Grunwald supports labs focusing on such topics as biochemical and molecular mechanisms that cause amyotrophic lateral sclerosis and exploring new roles of nuclear components where processing RNA depends on its location in the nucleus, for example.

“The genomic revolution has meant we now have incredible accurate and complex lists of cellular components,” Grunwald said. “The use of imaging is now but at my heart I am a tool about finally seeing where each of the components is organized maker and a physicist who deeply in space and time across scales cares about knowing how well from single cells to the whole human body.”

“Understanding the structure of the genome is essential to understand anything that has to do with regulation in cancer biology,” Strambio-De-Castillia said. “But at the bottom, the basis is often images. And only a small portion of what is contained in images can be tapped. So, CZI decided to invest in people who are in these roles, who are enabling this work every day. That is the science of images.”

Building on her pioneering work on integrated imaging pipelines for viral particle tracking, in collaboration with the Biomedical Imaging Group at UMass Chan, Strambio-DeCastillia was invited in 2018 to join the NIH’s 4D Nucleome Consortium as an associate member to develop microscopy and image analysis metadata standards.

Metadata is “information about other data” that is needed to interpret results, Strambio-DeCastillia said. It provides the essential context to ensure results can be properly evaluated, interpreted, reproduced and compared.

Strambio-De-Castillia connected with a larger project called the Open Microscopy Environment, an international consortium that developed an initial model for how to organize this information.

With CZI supporting her growing work in this field, Strambio-De-Castillia was invited to organize and lead the quality control and data management working group of Bioimaging North America (BINA). BINA is a consortium formed to bring together the bioimaging community in Canada, the United States and Mexico, to foster communication, data sharing and technology dissemination among core facilities; promote training and professional recognition for imaging scientists; and be a bioimaging advocate for institutional partners and funding agencies, with which to conduct strategic dialogue.

One of the key roles of BINA, now funded by CZI, is to serve as a counterpart to other global imaging organizations such as Global Bioimaging or the recently formed Quality Assurance and Reproducibility for Instruments & Images in Light Microscopy (QUAREP-LiMi) initiative. Strambio-De-Castillia’s work with QUAREP-LiMi to develop microscopy standards has been highlighted in numerous journals, including two articles in the July 2022 issue of Nature Methods.

Grunwald also participates in NIH’s 4D Nucleome Consortium and QUAREP-LiMi, among other organizations, bringing the richness of cutting-edge microscopy resources to UMass Chan labs and helping shape the future of scientific imaging.

Making science better

As Dr. Bargmann, formerly of CZI, said, “We’re in a position where we’re trying to build technologies for and with scientists that will accelerate biomedical science as a whole. We believe that we can develop these kinds of approaches across different fields and use them, together with our grantees and together with other partners, to move science forward.”

It's an exciting time for a physicist and a biologist to work across fields to accelerate discoveries.

“All of this is about making science better,” said Strambio-De-Castillia. “We are not expecting everybody to be data science experts. Everything is about enabling biomedical researchers to do what they love and what they do best.”

“The work that every student on this hallway and our talented colleagues in this institution do is extremely good work,” added Grunwald. “But I feel we are in the middle of a moment in which something is changing fundamentally. And to be on the forefront and to take full advantage of this needs exactly the sort of imaging initiative that is led by my laboratory and that of Dr. Strambio-De-Castillia.” ■