Quick Summary To figure out the labyrinthine-like puzzle of the brain, scientists need computational and quantitative biology skills

Professor Mark Goldman applies the quantitative skills he learned as a physicist to questions in neuroscience

Named to the Keizer Chair, Goldman will continue to make UC Davis a home for quantitative biology by ushering in a new quantitative biology major

Our brains are incredible biological machines synthesizing uncountable, chaotic sensory inputs into coherent experience. We populate a world of objects and each object—a computer screen, a red apple, even the shape and identity of your best friend—is visually perceived and interpreted to construct our reality.

“You see something that’s red; you see something that’s round. How do you know it’s a red circle?” asked Professor Mark Goldman. “You have these individual attributes and the idea is that there are different parts of our brain that are responsible for color, others that are responsible for form. How is the information carried by these pathways combined in a faithful, yet flexible manner?”

This concept of neural binding—what may underlie the miraculous coherence of consciousness— is just one of the many aspects of the brain that puzzle neuroscientists.

“How are we going to figure out the algorithms used by the neural networks of the brain?” asked Goldman, who holds appointments in the Department of Neurobiology, Physiology and Behavior and the Center for Neuroscience. “We’re not likely to uncover these directly from measurements of brain activity. We’re going to need computer models to interpret the data and to stimulate the formation of new hypotheses that, when tested experimentally, provide novel insights.”

An advocate for computational and quantitative biology, Goldman has been appointed to the Joel Keizer Endowed Chair in Theoretical and Computational Biology. The position honors the late Professor Joel Keizer, a pioneering UC Davis faculty member and theoretical biologist who spent 28 years on campus. He died on May 16, 1999 from lung cancer at the age of 56.

“I never had the honor of knowing Joel Keizer but I’ve certainly heard from my colleagues here about him, about how generous he was, about how he was a community builder,” said Goldman. “It’s obviously a huge honor.”

“Mark is ideally suited for the Keizer Endowed Chair,” said Executive Associate Dean of Academic Affairs John Harada, a professor in the Department of Plant Biology. “His research in theoretical and computational neuroscience is providing a foundation for linking information obtained at the cellular level to a system level understanding of animal behavior.”

Big data visualization techniques like this connectome—a computer-generated map of the brain pathways of 20 humans—inform neuroscience and help create models of complex biological systems. Andreas Horn/Max Planck Institute for Human Development

The big future of big data

A physicist by training, Goldman branched into neuroscience early in his career. He was fascinated by a simple question—what makes us tic?—and realized that any potential answers would be found in the domain of neuroscience. Mentored by Larry Abbott, currently a professor of theoretical neuroscience at Columbia University, Goldman sought to apply the quantitative skills he learned in physics to problems in neuroscience. It’s been a guiding desire ever since.

“We’re in the age of big data,” said Goldman. “We need to be able to integrate biology with the approaches of the mathematical sciences, the engineering sciences, and the physical sciences if we want to crack the big problems.”

Biology is becoming more and more quantitative. Innumerable biological data, like the kind generated from fields like genomics, only emphasize the need for computational and analytical skills. Questions like, “How does the genome influence behavior?” inherently require quantitative approaches, according to Goldman.

“How are we going to go from strings of four letters to understanding what that means biologically?” said Goldman. “At its core, it’s a computational problem.”

Teasing apart the function of the plethora of biochemical pathways underlying diseases such as cancer is also a computational problem, according to Goldman.

“To understand the detailed mechanisms underlying disease, we’re going to need computer models,” he added.

In Goldman's NPB 100L class, students recreate interactions in the brain. David Slipher/UC Davis

UC Davis, a home for quantitative biology

On top of research and teaching, Goldman is a pivotal player in developing a quantitative biology major at UC Davis. Though still in the design process, Goldman and colleagues are piloting new courses intended for the major. One that’s currently being explored is called Genome Hunters. In the class, students perform a mentored research project that relates features of an organism’s growth or behavior to its genome. This year, students learned about microbes and microbial growth, with an emphasis on the microorganisms found in high saline environments.

Students in Goldman's class discuss their experiment. David Slipher/UC Davis

“How the microbiome adapts to high salinity environments is important across a range of problems. For example, increased soil salinity is a critical issue in agriculture, which can affect the helpful bacteria that promote healthy soils and plant growth.” said Goldman. “The students are going to analyze the genomes from their different organisms to make sense of the variation in salt-tolerance among the microbes.”

Using quantitative techniques, the students will explore the genetic data to identify markers for salt tolerance in their studied bacteria.

Developing this new major isn’t just about making the College of Biological Sciences a place for quantitative biology. Goldman sees it as a university-wide effort.

“It’s a major initiative that is going to bridge all four undergraduate colleges,” he said.

That goal aligns with Keizer’s legacy. Throughout his career, Keizer worked at the nexus of math and biology, creating models for biological processes like insulin secretion and intracellular calcium dynamics, among many others.

“It really is about combining perspectives across disciplines to bring biology training and practice to the cutting edge,” said Goldman. “That’s something Joel was doing many years ago, and it’s only become more important.”

Through the quantitative biology major, Goldman will be sharing Keizer’s legacy with a new generation of students.

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