The maverick of big data

Dr. Gaudenz Danuser

Dr. Gaudenz Danuser forged his unique perspective while composing modern music, mathematically modeling data ranging from continental shifts to single-molecule dynamics, and motivating teams under extreme environmental conditions.

“I’ve always been an integrator of divergent subjects,” says the founding Chair of the Lyda Hill Department of Bioinformatics.

A maverick with the spirit to thrive in UT Southwestern’s “no fences” environment, which encourages interdepartmental collaborations, Dr. Danuser is a transformative thinker with the power to shake things up. He leads the University’s research efforts in bioinformatics, which he defines as the science of using computational methods to recognize patterns in biological data, i.e., the patterns of life.

Dr. Gaudenz Danuser

Prior to his 2013 arrival as a UTSW Professor of Cell Biology, he was a Professor at Harvard Medical School with an internationally recognized research program in quantitative imaging and computational modeling of cell dynamics.

Early in his career, he was on the faculty at his alma mater, ETH Zurich, when UT Southwestern Chair of Cell Biology Dr. Sandra Schmid – who was then Chair at The Scripps Research Institute – lured him to La Jolla, California, with a phone call asking, “What would it take to bring you on board?”

Having worked with Dr. Schmid for more than six years before moving to Harvard, Dr. Danuser says he welcomed another chance to collaborate with her. In fact, he rounded up a group of computational cell biologists to work in a “glass box” – a glass-walled room – located within the Schmid laboratory.

The lab within a lab on North Campus foreshadowed the Department of Bioinformatics’ new entrepreneurial and collaborative workspace on South Campus.

Modern art, including the color block paintings of Piet Mondrian, inspired the decor of UTSW’s Lyda Hill Department of Bioinformatics.

The area’s decor is inspired by Dutch artist Piet Mondrian’s color block paintings. It features open computing spaces with modular furniture where several faculty and visiting researchers from departments across campus as well as international visitors can sit down and get to work. Dry-erase markers are frequently used on the glass walls separating those rooms and on the walls of nearby spaces for small-group meetings, called huddle rooms.

Wrangling big data

In recruiting Dr. Danuser a second time, Dr. Schmid envisioned the need for wrangling enormous data sets – a requirement now increasing in virtually every field of basic and clinical research, and especially in the many fields impacted by advances in microscopy.

“Sandy has the ability to look ahead several years and see what’s on the horizon. She also has the feeling of not being bound by what the Department is. She has a way of seeing what the Department could be. When people say, ‘No one else is doing it that way,’ she can say, ‘Why not?’” he says.

Dr. Danuser, who holds the Patrick E. Haggerty Distinguished Chair in Basic Biomedical Science, arrived with recruitment awards from the Cancer Prevention and Research Institute of Texas (CPRIT) and the UT System STARs (Science and Technology Acquisition and Retention) Program. Since then, he has worked at tornadic speed to create a new culture for augmenting research across campus with bioinformatics tools.

Soon after his arrival in 2013, he called on his motivational skills for a project with Drs. Schmid, Biophysics Chair Michael Rosen, and Rama Ranganathan, former Director of the Cecil H. and Ida Green Comprehensive Center for Molecular, Computational, and Systems Biology, to launch UTSW’s Biomedical High Performance Computing (BioHPC) initiative. Five years after inception, BioHPC has grown to a self-organized consortium of 16 departments that share thousands of processors and 11 petabytes of data storage (1 petabyte equals 1 million gigabytes of data) to perform data-driven basic and clinical science.

(l-r) Lyda Hill and Dr. Gaudenz Danuser

BioHPC was already up and running when Dr. Danuser encountered another visionary: Dallas entrepreneur and philanthropist Lyda Hill, who donated $25 million to create the Department of Bioinformatics. “I never planned to be a chair of anything; but I agreed to this unique opportunity of starting a department from scratch – this was really cool,” he says with a laugh regarding his selection as Chair of Bioinformatics in 2015.

One of his first major studies after his arrival at UT Southwestern was designing and building a microscope capable of creating high-resolution, 3D images of living cancer cells in realistic, controlled microenvironments. To do so, he recruited Dr. Reto Fiolka, now Assistant Professor of Cell Biology and Bioinformatics, from the Howard Hughes Medical Institute’s Janelia Research Campus to UTSW. Together, they co-authored a study published in Developmental Cell in 2016 that describes the design of their unique microscope.

Now he is implementing his vision on how to best position UT Southwestern to capitalize on the power of bioinformatics. Dr. Danuser says he wants to create a computer science department in a medical center to provide the tools necessary for the rapidly increasing challenges of managing and analyzing extremely large data sets in all areas of biomedicine. That work encompasses collaborations, featuring Bioinformatics faculty “integrators,” that carry the potential to quickly benefit patients.

Members of the research team that helped build and test a microscope capable of creating 3D images of living cancer cells included (l-r) Drs. Kevin Dean, Gaudenz Danuser, Erik Welf, Claudia Schäfer, Reto Fiolka, and Meghan Driscoll.

Much of the integration between the Department and campus is accomplished via the Bioinformatics Core Facility (BICF) – funded with a $5.6 million CPRIT grant – serving as a resource for the entire University. Often the BICF Help Desk is the first point of contact for researchers interested in finding clever ways to incorporate bioinformatics into their research, he says.

As an academic department, Bioinformatics also needs a subset of faculty members, whom Dr. Danuser calls the “innovators,” working to develop the computational tools of tomorrow. Those efforts are intended to keep the University at the forefront of bioinformatics for the next 75 years using artificial intelligence, computer vision, and genomics.

“Every single laboratory in my Department – mine and five others – does artificial intelligence,” he says. The Department’s 10-year plan includes tripling this faculty. Dr. Danuser hopes to recruit investigators with expertise in several types of genomics as well as in neuroinformatics.

“I look forward to working more closely with the Peter O’Donnell Jr. Brain Institute. We are at this interesting point where understanding the brain inspires the creation of artificial intelligence to better understand the brain, among many other things,” he says.

A divergent mind

Dr. Danuser traces his horizontal thinking skills to his early scientific career, beginning with the European equivalent of a master’s thesis on earthquake prediction. That study resulted in an invitation to speak at the Jet Propulsion Laboratory in California.

“Computer vision is one of the fields of artificial intelligence – it’s actually sort of the ‘mother application’ of all artificial intelligence. Since humans were first able to build computers, they’ve wanted to make computers see.”

Dr. Gaudenz Danuser

After modeling GPS data of the movements of continental plates, he worked as a young engineer leading surveying teams on massive water dam projects in the Swiss Alps. He attributes his widely acclaimed motivational skills to this period in his career.

“They’d drop us off from a helicopter near a shelter with enough food for four days. We had to measure through the protocol – in snow, rain, or sunshine – before the helicopter returned to pick us up,” he explains.

From that grand scale he turned his attention to the micro level, seeking a Ph.D. in electrical engineering/computer science, which led him to computer vision and its biomedical applications.

“Computer vision is one of the fields of artificial intelligence – it’s actually sort of the ‘mother application’ of all artificial intelligence,” he says. “Since humans were first able to build computers, they’ve wanted to make computers see. My Ph.D. was on building a computer system that could see very, very fine micrometer-sized objects and manipulate them under completely intelligent control. We would say, ‘OK, go grab that object,’ and the machine would then navigate to that object autonomously. I wrote that software.”

Dr. Danuser passed up several computer science job offers to pursue postdoctoral research at the Marine Biological Laboratory in Woods Hole, Massachusetts, where he designed imaging methods to look at individual living cells.

“I realized one of the coolest applications of microscopy is cell biology,” he says, adding that he never saw himself in basic science, thinking instead he would go into industry. Despite those career goals, he quickly became known in scientific circles for his unique combination of interests.

“I was the guy who did cell biology with computers,” he says.

Quantitative 3D live cell imaging of a primary melanoma cell

Ever since then, his research has combined computer vision, cell biology, and advanced microscopy. His UT Southwestern research program in Cell Biology includes clinically relevant studies of lung, skin, and pediatric cancers with innovative ex vivo and in vivo live cell imaging and computational modeling to identify cellular mechanisms at the intersection of cancer cell development, plasticity, and survival.

New ways of seeing

Structure is essential in cell biology, as it is in the creation of a new department that aims to encourage collaboration, he says. To further cross-campus collaborations, the Department recently issued its first call for project proposals that will pair a faculty member from anywhere on campus with one from Bioinformatics. The Department also provides two seminar series, one within the Graduate School of Biomedical Sciences and another on artificial intelligence co-hosted with the Department of Radiation Oncology.

“I see informatics as the backbone of everything we do in biomedical science,” Dr. Danuser says.

He predicts the next wave of innovation in bioinformatics will involve the science of perception in order to improve our ability to understand the big data we are generating. The complexity and volume of sophisticated data sets will require new ways of seeing, perhaps encompassing more than vision alone, he says.

“The old x- and y-axis everyone learned in school is too limited for robust interpretation,” he explains. “We may need to incorporate sound or touch in addition to vision to reach a deeper understanding of the data.”

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Dr. Rosen has an appointment in the Cecil H. and Ida Green Comprehensive Center for Molecular, Computational, and Systems Biology and holds the Mar Nell and F. Andrew Bell Distinguished Chair in Biochemistry.

Dr. Schmid holds the Cecil H. Green Distinguished Chair in Cellular and Molecular Biology.