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25 Jul 2025
6 Min Read
Dr Lee Khai Wooi (Academic Contributor), Nellie Chan (Editor)
In the world of vaccine research, purification is often one of the most time-consuming and resource-intensive steps. It’s a bottleneck that can slow down the production of life-saving biologics, especially in countries where access to advanced equipment is limited. But what if the solution was hidden in something as simple as a failed experiment?
At Taylor’s University, Dr Lee Khai Wooi is leading a research project that flips conventional wisdom on its head. By using metal ions to trigger the aggregation of virus-like particles (VLPs), he’s developed a low-cost, scalable method of purification that could one day help Malaysia to produce its own vaccines—without the need for complex infrastructure.
Dr Lee is a senior lecturer at the School of Biosciences, where he specialises in molecular virology and nanobiotechnology. His latest work takes a new approach to a well-known problem: the purification of VLPs, which are essential in developing safe and effective vaccines for diseases, such as human papillomavirus (HPV) and hepatitis B virus (HBV).
While traditional methods rely on chromatography—which requires expensive equipment, skilled staff, and extensive time—Dr Lee’s technique offers an alternative: using metal ions to aggregate the VLPs, allowing for easier separation from the surrounding solution even in low-resource settings.
We spoke with him to understand the science behind his work, the challenges he’s faced, and what this innovation could mean for global health.
Q: What sparked the idea behind using metal ions to purify VLPs?
A: It started with a failed experiment. A former PhD student came to me, frustrated that his VLPs had clumped together—or aggregated—rather than remaining soluble after IMAC (Immobilised Metal Affinity Chromatography) purification. We suspected that metal ions had leached from the column and caused the aggregation. But instead of seeing it as a setback, I began to wonder—what if this process could be controlled? Could we actually use aggregation as a method of purification?
Q: How does this method work compared to traditional VLP purification?
A: Traditional methods like chromatography are effective, but they can be time-consuming, expensive, and equipment-intensive. In contrast, our approach uses metal ions to induce aggregation in VLPs that have multiple histidine tags. These tags interact with the metal ions, causing the particles to clump together. We can then isolate them through simple centrifugation—or in some cases, gravity alone.
Q: Is this method limited to certain types of VLPs?
A: It works especially well for VLPs with histidine tags, since those tags are naturally attracted to transition metal ions like nickel or cobalt. We’ve also found that factors like pH and ion concentration can be adjusted to control the aggregation more precisely. On the other hand, proteins with only a single histidine tag don’t aggregate as effectively, highlighting the importance of multiple tags for this method to work well.
Q: What makes purifying VLPs such a difficult challenge?
A: Many people assume that once VLPs are produced, the hard part is over. But purification is often one of the most technically challenging and expensive steps. This is especially true when the final product must meet the strict standards set by the US Food and Drug Administration (FDA) and Good Manufacturing Practice (GMP) guidelines.
Q: What were some of the biggest challenges in developing this technique?
A: One major challenge was proving the underlying mechanism. Some believed the particles were aggregating non-specifically, but we had a strong suspicion that histidine-metal interactions were the real cause. We needed clear scientific evidence to confirm that.
Q: How did you overcome that hurdle?
A: We collaborated with Professor Philipp Kukura’s lab at the University of Oxford, which specialises in mass photometry—a technique that enables single-molecule analysis. Using this method, they showed in real time how the VLPs interact with metal ions and begin to clump together. It gave us direct visual evidence that histidine-metal binding is indeed the driving force behind the aggregation.
Q: Did you face any practical obstacles beyond the science itself?
A: Yes—funding and access to resources were definitely challenges. Scaling up the work required prototyping support, and I’m grateful that Taylor’s University offered seed funding to help us move forward.
Q: What kind of difference could this method make outside the lab?
A: It has the potential to significantly reduce the cost and complexity of biologics production. In low- and middle-income countries, where access to chromatography equipment is limited, this method could be a game-changer. All you need are the right conditions and a centrifuge to separate your product.
Q: Is this relevant to Malaysia’s broader health goals?
A: Absolutely. Under the National Vaccine Development Roadmap (NVDR), Malaysia is aiming for vaccine self-sufficiency within the next decade. But for that to happen, we need cost-effective and scalable manufacturing methods. This research offers one such path.
Q: Could this method be applied beyond VLPs?
A: Yes, this method could be adapted to purify other biologics, not just VLPs. It has the potential to make manufacturing more efficient and reduce the cost of medicines worldwide, which is especially important for underserved communities.
Q: What keeps you motivated to work in this area?
A: I think what drives me is a sense of practicality. There’s a lot of cutting-edge science out there, but I’ve always been more interested in research that solves real-world problems. It’s not just about publishing papers—it’s about whether your work can actually be used.
Q: How has your experience as an educator influenced your approach to research?
A: Teaching subjects like microbiology, biotechnology techniques, and scientific instrumentation has kept me grounded in the fundamentals while helping me stay attuned to emerging technologies. It’s also sharpened my ability to communicate complex ideas clearly—an essential skill both in the classroom and when designing research that’s practical and applicable. Engaging with students brings fresh perspectives and reminds me why curiosity and clarity are so central to scientific inquiry.
Q: Any advice you’d give to young researchers starting out?
A: Stay curious, stay practical, and stay resilient. Focus your research on solving real problems—not just publishing for the sake of it. Master the fundamentals, ask clear questions, and don’t be discouraged by failed experiments or negative results. These experiences often reveal what doesn’t work—but just as importantly, they can point you towards what might. And above all, be patient. Good research takes time, iteration, and a commitment to continuous learning.
Dr Lee’s work is still in its early stages, but the implications are significant. By developing a purification technique that is fast, scalable, and low-cost, he’s paving the way for more equitable access to biologics, particularly in countries where such access has long been out of reach.
The next steps? Testing the method on a wider range of proteins and scaling it for industrial application. If successful, this approach could help Malaysia—and other nations—move closer towards vaccine self-sufficiency.
In a world where innovation is often defined by complexity, Dr Lee’s research is a reminder that sometimes, the simplest ideas are the most powerful.
