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Bringing a physicist’s mindset to the biosciences

UCLA’s Gerard Wong approaches life sciences with an eye for connection and a distrust of metaphors

By Wayne Lewis

Gerard Wong (Image credit: UCLA Samueli)

This article was originally published by UCLA Newsroom

In his lab, Gerard Wong, professor of bioengineering at the UCLA Samueli School of Engineering, explores the molecular mechanisms behind basic processes of life and their influence on human health. But his original training was far afield — in physics, working with solids and liquids at the smallest scales.

That shift in scientific focus isn’t unprecedented, but the way Wong bridges the disparate disciplines is unusual. By applying not only instrumentation but also ideas from physics to biology, he has uncovered surprising links between the fields, which could have implications for bioscience and disease treatment.

“Taking that route means that I fit into many academic departments equally badly, and from a different perspective, equally well,” said Wong, also a professor of chemistry and biochemistry at the UCLA College and a member of the California NanoSystems Institute at UCLA. “Physicists are guided by notions of generality, such as the very idea of physical laws, whereas biologists are interested in the rich manifestations of specificity, so the two are not always on the same page. Nevertheless, the language of physics can, at times, be quite powerful in thinking about a broad range of biological phenomena.”

For instance, one part of his current research program focuses on autoimmune diseases, which are typically viewed as a malfunction in a coordinated defense system. He aims to reveal how inflammation works at a more fundamental level, as a system that obeys physical laws.

“We imagine that the immune system recognizes something in a similar way to how we recognize something: This is DNA, this is RNA, this other thing is a part of the bacterial flagellum,” Wong said. “Nature might instead work through geometric shapes and sizes, entropy, interaction or lack of interaction with water, interactions between charged particles — in terms of the excruciatingly low-level, detailed, unifying language of physics.”

Taking this approach, the researchers revealed how certain molecules amp up the immune response, which can have applications to lupus, psoriasis, arthritis and other diseases.

Another research focus is studying basic processes that occur at cell membranes. What Wong and his colleagues learn could inform new ways to kill dangerous bacteria and fungi by sabotaging their membranes to overcome bugs’ resistance to antibiotics.

The physicists’ twist

The researchers use concepts to describe how membranes curve and change shape — needed to form holes or for cells to divide — that echo Albert Einstein’s methods for characterizing the fabric of space-time, although the vocabulary used in the two fields differs slightly.

Wong also studies biofilms, socially organized communities of bacteria that live on surfaces. Biofilms can be harmful in the lungs of people with cystic fibrosis. But they can be helpful, for example, in the human gut to help digest vegetables. So, controlling biofilms could be beneficial.

That’s why Wong seeks to comprehensively profile the mechanisms behind biofilm formation, from the moment a bacterium senses a surface to the internal signaling that prompts it to settle down — to what causes its progeny to stay with the community instead of swimming away.

By following bacterial colonies over time, Wong’s lab came to an unexpected conclusion. Signals that influence whether a given cell joins a biofilm, the researchers found, seem to be encoded in the pattern of how the concentration of a certain molecule fluctuates in a family of cells over time.

Key biological processes are currently thought to be directly controlled by increases or decreases in certain molecular messengers, like a light switch being flipped on or off. Wong’s team showed that biofilm formation is partly controlled by the rhythm with which messages are delivered, similar to how a radio signal is encoded. If this time-based biological signaling is widespread, it could have major implications for biomedical research and care — including how drugs are designed.

Mind your metaphors

There is value to questioning metaphors that guide our thinking, Wong says.

“Why should it be like flipping a molecular switch on and off, just because the idea of a switch is commonplace in our present technological experience?” he asked. “Why shouldn’t it be more complicated and natural to the world of molecules? We know that molecular activity fluctuates.”

Wong is grateful to have found scientific fellow travelers at UCLA and beyond who support his approach to biology.

“We’ve been very fortunate to have great collaborators who are good at what they do and are open-minded enough that they don’t immediately laugh me out of the room,” he said. “That environment is quite conducive to research that’s interesting and impactful.”

While in graduate school studying physics at UC Berkeley, Wong became interested in the seemingly small biological differences that can lead to major consequences for health. As a postdoctoral researcher he worked with physicist-turned-biologist Cyrus Safinya at UC Santa Barbara, who had connected his own early work on liquid crystals to the study of how biological systems seem to spontaneously self-assemble — and potential applications of these ideas to nonviral gene therapy.

Though Wong encountered dead ends and mistakes on the path from physics to bioscience, he also gained a fresh perspective.

“Engaging a field with some humility is always good,” he said. “I don’t mean humility in the sense of, ‘Aw, shucks,’ I mean the humility that comes from allowing that the phenomenon you’re looking at might not actually be what you think it is, or what you find to be most interesting initially may turn out not to be important.”