Understanding how living cells perform “quality control” and keep diseases at bay

When he was growing up in a village in Shantou, China, he would go to the wet market with his mother, where she tasked him with working out their payments for fresh fish and produce and the change due. From this seemingly mundane routine of everyday life, he developed a strong drive for math and science.

“Although my mom was a Chinese-language teacher, she saw the importance of early education in math and took every opportunity to guide me,” said Presidential Young Professor Lin Zhewang, who went on to get a string of academic scholarships as well as awards, and started his own lab at NUS Biological Sciences in September 2021. He now studies vital molecular mechanisms that control the quantity and quality of protein synthesis in living cells, and how these mechanisms protect the cells from disease.

He already has a solid track record. In 2020, he was the lead author in a Science paper that documented a crucial protein that controls the amount of tubulin in a cell. Tubulin is a structural molecule that forms the cell’s internal “skeleton”. There are different varieties of tubulin and they have to be present in the correct proportions and configuration for many important functions from molecular transport to cell division.

Assistant Professor Lin began specialising in this topic during his postdoctoral stint at the MRC Laboratory of Molecular Biology in Cambridge. For 40 years, scientists had tried to understand the mechanisms of cellular quality control, but with little success as they did not have the right molecular tools. But by the time he entered the field, new molecular markers had been developed that could detect and bind to specific chemical structures when activated by ultraviolet light, enabling him to “see” the molecular machinery of the cell more clearly.

Journey of ups and downs

Asst Prof Lin’s research specialty started taking shape when, as an undergraduate, he got a letter from Cornell University in the US, inviting him to do a PhD in chemical biology there. It was a once-in-a-lifetime opportunity to explore his favourite subject.    

When he got to Cornell, his new advisor showed him how the lab was able to use basic chemical principles to deduce the unknown biological properties of molecules from their chemical structure alone.

“I was amazed by the power of chemistry in solving important biological questions,” said Asst Prof Lin. “I saw the opportunity of harnessing chemical knowledge to do biology because after all, biology at the molecular level is chemistry.”

As he embarked on his research career, Asst Prof Lin would wield this powerful approach to accurately identify biological molecules and make groundbreaking discoveries of what those molecules do in living cells.

But the journey was not easy. He had to deal with endless failed experiments, a rite of passage for a PhD student. On top of that, he got married halfway through it, which his lab-mates at Cornell helped organise. Alas, the newlyweds had no honeymoon as he simply ran out of time. But once a year, one of them made the transatlantic flight to visit the other.

When Asst Prof Lin felt his PhD was going badly, he took time off to cook. He figured out a way to roast Peking duck in an oven while keeping its skin crispy. The duck is usually roasted over a wood fire. Instead, he stuck a beer bottle in the bird’s bottom so it stood upright above the oven tray, preventing the collected juices from wetting the skin. After that, he felt confident again to tackle the experimental challenges in the lab. His efforts ultimately paid off, and he won a departmental prize for his academic achievements.

When he moved on to his postdoc, he also took on a “night-time job” – taking care of his baby son. It was stressful, but he “trained” the toddler to sleep through the night without waking up by adjusting the milk feeding timings. As a result, he could have a good night’s rest and wake up all refreshed for research.

“I planned all the experiments very carefully and did things very efficiently although I had limited time in the lab,” he said – to such an extent that his colleagues said his project was going at the “speed of light”.

Giving back to society

Over the past two years, the COVID-19 pandemic has infected Asst Prof Lin’s lab with a quest to find a universal method for protecting people against all SARS-type (severe acute respiratory syndrome) viruses, such as those that caused the SARS outbreak in 2003, MERS (Middle East respiratory syndrome) in 2012 and now COVID-19. Existing measures like vaccines and antiviral drugs usually target specific variants of a virus; the virus can bypass these defences simply by mutating into another variant.

The lab is now trying to find a universal molecular vector in the human cell that the virus uses to hijack the cell. If this vector can be disabled by some drug, it will stop the virus in its tracks no matter how it mutates. Asst Prof Lin’s lab is particularly suited to this work because it has developed the appropriate molecular tools as part of its overall research theme.