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Neuroscience

Peng Zou

Cellular cartographer is mapping proteins and nucleic acids in action

by Laura Howes
August 25, 2019 | APPEARED IN VOLUME 97, ISSUE 33

09733-cover13-profile.jpg
Credit: Courtesy of Peng Zou/Angew. Chem., Int. Ed./Shutterstock/C&EN
09733-cover13-research.jpg
Credit: Adapted from Angew. Chem., Int. Ed./Yang H. Ku/C&EN
To create a detailed map of a cell, Zou uses engineered enzymes to tag biomolecules like RNA in mitochondria with chemical probes (red). After purification to separate out the tagged molecules, he applies high-throughput techniques to glean information about what's happening in specific parts of a cell.

Vitals

Current affiliation: Peking University

Age: 34

PhD alma mater: Massachusetts Institute of Technology

Role model: “Roger Y. Tsien. He was an inspiring and creative scientist, and his work on calcium imaging and fluorescent proteins has revolutionized biological research.”

If I weren’t a chemist, I would be: “An astronomer perhaps. I enjoyed stargazing as a child and was deciding between studying chemistry and astronomy before entering college. I eventually chose chemistry because it offers the opportunity to do experiments rather than simply observing what is happening in nature.”

Must-have in the lab: “Our microscopes.”

Must-have on the road: “Universal multiplug adapter.”

3 key papers

“Hybrid Indicators for Fast and Sensitive Voltage Imaging” (Angew. Chem., Int. Ed. 2018, DOI: 10.1002/anie.201712614)

“Bright and Fast Multicoloured Voltage Reporters via Electrochromic FRET” (Nat. Commun. 2014, DOI: 10.1038/ncomms5625)

“Proteomic Mapping of Mitochondria in Living Cells via Spatially Restricted Enzymatic Tagging” (Science 2013, DOI: 10.1126/science.1230593)

For Peng Zou, the joy of science is in assembling puzzles. The chemist, based at Peking University, is developing tools to study biology in living systems, combining expertise from different fields to see how biomolecules are arranged in a cell. His goal is to understand how the chemistry happening inside cells can cause neurodegenerative diseases, like Alzheimer’s disease and amyotrophic lateral sclerosis.

“In biochemistry, we would usually like to take cells apart to understand them in chemical terms,” Zou says. “But to really understand how cellular functions arise from all these molecular components, we need to put everything back together in the cell.”

To do that, Zou’s lab is developing chemical reactions and custom-built microscopes and software to label relevant biomolecules and visualize signaling inside a live cell.

One challenge has been developing a way to tag individual cellular components in a small, precise area. To combat this issue, Zou and his lab use biology to help generate free radicals inside living cells. These reactive but short-lived free radicals allow him to tag molecules in just one part of the cell, leaving the rest of the cell untouched. The method lets Zou add spatial dimensions to high-throughput techniques like mass spectrometry or nucleic acid sequencing.

After first working on a technique for labeling proteins during his PhD, Zou recently extended the approach to also label nucleic acids. So far, he has demonstrated that the technique works by labeling mitochondrial RNA but says he will be doing more. Eventually Zou hopes to be able to stitch together a mosaic of snapshots in time and space to understand how proteins and nucleic acids assemble in the 3-D space of the cell and how their construction differs in a disease like Alzheimer’s. “We are trying to create a molecular map of the cell,” Zou says.

While Zou maps the complexity of a living cell, he jokes that a map of his own career moves would be rather simple. If you were to plot his journey, he says, “the graph would look a little bit boring because there are only two cities I’ve been to.”

For his PhD at the Massachusetts Institute of Technology, Zou trained in proteomics and imaging with Alice Ting, now at Stanford University. He then completed a postdoc with Adam Cohen at Harvard University, where he developed fluorescent reporters to make the voltages between neurons visible. In 2015, Zou moved back to Peking University to start his own group and study the chemical reactions that make the brain function.

His work is more than just a matter of curiosity. Understanding where and how proteins and nucleic acids are made inside a cell and how cells communicate could give researchers novel insights into the mechanisms of intractable diseases. Those insights could also potentially allow him to create models to screen for new drugs. Zou is collaborating with neurobiologists to apply his lab’s techniques to study several cell models of neurodegenerative diseases.

With his background and skills, Zou has made his own research niche, Ting says. By assembling expertise in techniques like molecular biology, omics, and optogenetics, she says, he’s “uniquely positioned to tackle the brain.”

 
Credit: Courtesy of Peng Zou/Angew. Chem., Int. Ed./Shutterstock/C&EN

For Peng Zou, the joy of science is in assembling puzzles. The chemist, based at Peking University, is developing tools to study biology in living systems, combining expertise from different fields to see how biomolecules are arranged in a cell. His goal is to understand how the chemistry happening inside cells can cause neurodegenerative diseases, like Alzheimer’s disease and amyotrophic lateral sclerosis.

“In biochemistry, we would usually like to take cells apart to understand them in chemical terms,” Zou says. “But to really understand how cellular functions arise from all these molecular components, we need to put everything back together in the cell.”

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To do that, Zou’s lab is developing chemical reactions and custom-built microscopes and software to label relevant biomolecules and visualize signaling inside a live cell.

One challenge has been developing a way to tag individual cellular components in a small, precise area. To combat this issue, Zou and his lab use biology to help generate free radicals inside living cells. These reactive but short-lived free radicals allow him to tag molecules in just one part of the cell, leaving the rest of the cell untouched. The method lets Zou add spatial dimensions to high-throughput techniques like mass spectrometry or nucleic acid sequencing.

After first working on a technique for labeling proteins during his PhD, Zou recently extended the approach to also label nucleic acids. So far, he has demonstrated that the technique works by labeling mitochondrial RNA but says he will be doing more. Eventually Zou hopes to be able to stitch together a mosaic of snapshots in time and space to understand how proteins and nucleic acids assemble in the 3-D space of the cell and how their construction differs in a disease like Alzheimer’s. “We are trying to create a molecular map of the cell,” Zou says.

While Zou maps the complexity of a living cell, he jokes that a map of his own career moves would be rather simple. If you were to plot his journey, he says, “the graph would look a little bit boring because there are only two cities I’ve been to.”

For his PhD at the Massachusetts Institute of Technology, Zou trained in proteomics and imaging with Alice Ting, now at Stanford University. He then completed a postdoc with Adam Cohen at Harvard University, where he developed fluorescent reporters to make the voltages between neurons visible. In 2015, Zou moved back to Peking University to start his own group and study the chemical reactions that make the brain function.

His work is more than just a matter of curiosity. Understanding where and how proteins and nucleic acids are made inside a cell and how cells communicate could give researchers novel insights into the mechanisms of intractable diseases. Those insights could also potentially allow him to create models to screen for new drugs. Zou is collaborating with neurobiologists to apply his lab’s techniques to study several cell models of neurodegenerative diseases.

With his background and skills, Zou has made his own research niche, Ting says. By assembling expertise in techniques like molecular biology, omics, and optogenetics, she says, he’s “uniquely positioned to tackle the brain.”

Vitals

Current affiliation: Peking University

Age: 34

PhD alma mater: Massachusetts Institute of Technology

Role model: “Roger Y. Tsien. He was an inspiring and creative scientist, and his work on calcium imaging and fluorescent proteins has revolutionized biological research.”

If I weren’t a chemist, I would be: “An astronomer perhaps. I enjoyed stargazing as a child and was deciding between studying chemistry and astronomy before entering college. I eventually chose chemistry because it offers the opportunity to do experiments rather than simply observing what is happening in nature.”

Must-have in the lab: “Our microscopes.”

Must-have on the road: “Universal multiplug adapter.”

Research at a glance


Credit: Credit: Adapted from Angew. Chem., Int. Ed./Yang H. Ku/C&EN

To create a detailed map of a cell, Zou uses engineered enzymes to tag biomolecules like RNA in mitochondria with chemical probes (red). After purification to separate out the tagged molecules, he applies high-throughput techniques to glean information about what's happening in specific parts of a cell.

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