In 1978, scientists revealed the first samples of synthetic human insulin, produced from genetically-engineered Escherichia coli bacteria rather than painstakingly extracted from animal organs. This feat would enable the mass production of a life-saving hormone, revolutionising the way we would treat diabetes—a disease that, in its type 1 form, once killed patients within five years of diagnosis.
Since that turning point, the field of synthetic biology has made significant advances in harnessing the cellular machinery found in diverse species, enabling us to not only create living, single-celled factories to efficiently produce biofuels and medicines, but also customise our own immune cells to fight challenging diseases.
Drawn by the field’s potential to make waves in multiple sectors, A*STAR National Science Scholar Miselle Tiana Hengardi is currently pursuing her PhD studies in synthetic biology at A*STAR’s Singapore Institute of Food and Biotechnology Innovation (SIFBI). Her work focuses on the engineering of baker’s yeast to produce potential active ingredients for eco-friendly sunscreens on an industrial scale.
In this interview with A*STAR Research, Hengardi shares her research journey, her experiences in the field of synthetic biology, and her excitement for its future prospects.
Tell us about your scientific journey.
My first research project was back in secondary school. My groupmates and I ambitiously attempted to make a soap prototype which could remove the smell of durian from one’s hands. Although our final prototype—which contained components such as ground durian husk and honey—did unfortunately turn mouldy after a few days, the project kindled my interest in using science to improve everyday lives.
Under the A*STAR National Science Scholarship, I pursued a degree in chemical engineering at Imperial College London, UK. While there, I explored as many different research areas as I could to identify one that resonated with me the most. My projects ranged from developing green tea complexes for rheumatoid arthritis treatment with A*STAR’s former Institute of Bioengineering and Nanotechnology, to optimising a drug formulation in a miniature pharmaceutical manufacturing unit with the Massachusetts Institute of Technology, US.
After four years abroad, I did a one-year research attachment at the Institute of Materials and Research Engineering (IMRE), where I attempted to incorporate waste plastic into bitumen. This stint really helped me to re-acclimatise to the research landscape at A*STAR and in Singapore.
With the breadth of exposure I had received, I eventually chose to pursue a PhD degree in synthetic biology at SIFBI, aided by the A*STAR Graduate Scholarship. Its support has enabled me to attend three overseas conferences, one of which—specifically, a talk at a summit in Lisbon, Portugal—sparked an idea which eventually made its way to my first published paper. I also discovered the joy of sharing my research when presenting posters at two other conferences in Seoul and Edinburgh.
While these were eye-opening experiences, I would have gotten nowhere without the guidance of my PhD advisor and senior colleagues at A*STAR. No scientific journey is perfectly smooth-sailing, so I’m immensely thankful to the mentors who helped me navigate through rocky waters.
What fascinates you about synthetic biology?
Synthetic biology essentially means the engineering of organisms or systems to perform functions that they don’t exhibit in nature. It’s yielded significant advances across various domains: think of the efficient production of insulin and the antimalarial drug artemisinin in microbial hosts, or the generation of ethanol and biodiesel, or even biomedical technologies such as personalised CAR-T cells for specific cancer treatments. The field’s diverse range of applications greatly appeals to me.
It’s also vital to explore synthetic biology’s implications. During a driving lesson last year, my instructor spent 10 minutes urging me to switch fields after getting to know the nature of my work; he shared his belief that genetic engineering is unethical and goes against a sense of natural order. For me, his vocal and staunch opposition not only underscored the ongoing challenge of garnering public acceptance, but also highlighted the need to consider the ethical and societal dimensions of our work.
Synthetic biology researchers need to address these issues for the field to flourish sustainably and responsibly. Nonetheless, I do believe that synthetic biology is a potent tool for tackling some of the modern world’s challenges, and that we can implement its solutions ethically.
Tell us about your current work at SIFBI.
While sunscreens offer protection against ultraviolet (UV) radiation, few realise that some artificial UV filters in sunscreens can adversely impact human health and the environment. Some sunscreen components, such as oxybenzone and octinoxate, can induce allergic reactions in humans, while sunscreens washed off into aquatic ecosystems can also result in coral bleaching.
Nature offers an eco-friendly alternative—microbial sunscreen compounds produced by certain marine algae, seaweeds and fungi. Unfortunately, these compounds are produced in very low amounts in their natural hosts.
At SIFBI, my PhD project focuses on engineering Saccharomyces cerevisiae—known to most as baker’s yeast—to produce enhanced yields of natural sunscreen compounds known as mycosporine-like amino acids, or MAAs. We aim to make MAAs economically viable as an active sunscreen ingredient, with the ultimate goal of developing an MAA-based sunscreen that’s both effective and environmentally friendly.
Recently, we published a paper showing that blocking a metabolic step in yeast can boost MAA production ninefold. As MAAs share an intermediate with other valuable metabolic compounds like antibiotics (such as septacidins and hygromycin B), similar engineering approaches could likewise enhance their production. We’ve also engineered an enzyme to produce multiple MAA variants, and recently filed a patent for this development.
What excites you about your journey ahead?
There’s a multitude of things to discover and fields to explore! I am drawn to many scientific disciplines and excited to further diversify my knowledge and expertise. A*STAR also fosters interdisciplinary collaborations between scientists from very different fields. I look forward to growing as a scientist, and hope to eventually leave my mark in the scientific community. It would be particularly gratifying to witness my research translating into real-world impact.
I would also like to contribute to effective scientific communication both in an individual capacity and as part of a collective effort. After all, to make enduring contributions, it’s crucial for scientists to garner the public’s acceptance and uptake. Moreover, the importance of passing on the baton to future generations to advance scientific endeavours should not be understated.
What advice do you have for other aspiring young scientists?
I feel quite underqualified to offer advice, considering that I still have such a long way to go myself! But if there’s one thing I’ve learned so far, it’s the old adage that “change is the only constant in life”. In the ever-changing landscape of research, the ability to adapt to new skills, new problems and new situations is increasingly important. Hence, I’d encourage others to explore as many fields as they can to build versatility.
Apart from being consistent and persistent in your scientific quests, it’s important to nurture hobbies outside the lab. After all, on days when mental gymnastics cannot help you make sense of the data, a good break can do wonders.
